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298 Cards in this Set

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What types of biochemical lesions are involved in the etiology of chronic diseases?
Amino acid substitutions/deletions in protein primary structures that can affect structure and function. Toxicants may also change cell structural components or may block enzyme active sites.
How does the early detection of nutrient deficiency prevent chronic degenerative disease?
Intervention to restore nutrient levels promotes normal cellular and tissue function.
How do standard therapeutic interventions for heart disease or depression affect a patient's nutritional status?
e.g. statins, SSRIs - can exacerbate underlying nutrient insufficiencies or toxic effects
As of 2001, how many genetic mutations of PAH were known to cause some variant of PKU? Name the enzyme PAH.
More than 400. Phenylalanine hydroxylase.
What other enzyme is a principal cause of PKU? How is it involved in the clearance of excess L-phenylalanine?
GTP cyclohydrolase. It is involved in the formation of BH4 (tetrahydrobiopterin) which is a required coenzyme for PAH.
For enzymes with vitamin-derived cofactor requirements, is there any difference between the clinical outcome from a genetic alteration in the protein structure and dietary deficiency of the nutrient required for production of the cofactor?
Lack of enzyme activity will manifest the same. However, differences may arise in the age of onset and severity of outcome (more severe effects are usually only seen with genetic alterations).
Why is it unusual to find elevated lipid peroxides when fat-soluble vitamins in serum are in their upper ranges? What other nutrients may therefore need evaluation?
Fat soluble vitamins protect against lipid peroxide formation via oxidative stress. May need to evaluate PUFAs, since this scenario may indicate elevated levels of these easily-oxidized FA in membranes.
Which vitamin insufficiencies are indicated by elevated branched chain keto acids in urine?
B1, B2, B3, B5, lipoic acid
How does urinary formiminoglutamate testing add clinical insight to homocysteine testing? What acronym is commonly used for formiminoglutamate?
Formiminoglutamate evaluates folate status. Folate deficiency can be ONE cause of elevated homocysteine. FIGLU.
Why is 'folic acid' deficiency a misnomer? What is the correct term?
Folic acid is not an essential nutrient, nor does it generally occur in foods. The correct term is 'folate deficiency.
What is the active form of folate?
tetrahydrofolate.
Why does direct testing of calcium in serum fail to reveal nutritional status of calcium?
Serum calcium is very tightly regulated by PTH (from parathyroid, when Ca++ falls) and calcitonin (from thyroid parafollicular cells, when Ca++ rises).
What organ failure most directly causes multiple low trace elements to be found in blood/urine? Why do such patients frequently only show slowly-improving trace element status when supplemented with those minerals only?
Stomach - failure of HCl output. Supplementation of trace elements without HCl doesn't effectively correct the issue. Properly timed pH shifts are required for delivery of elemental salts for absorption in the small intestine.
What other nutrient is commonly required as an intermediate ligand for element absorption?
Free amino acids and small peptides from dietary protein.
What effect does specimen transport have on relative levels of glutamate and glutamine?
Gln converts to Glu when specimen analysis is delayed or warmed.
What are the competing demands for homocysteine and how can oxidative stress cause imbalance between these pathways?
Hcys can be transulfurated to (eventually) form glutathione or methylated to form methionine. Excess oxidative stress can pull hcys into the transfulfuration pathway, leaving less availability for methionine, and subsequent methylation factors like SAMe.
What places the greatest demand on absorbed amino acids? Protein synthesis, neurotransmitters or sex hormones?
Protein synthesis, by far.
What organs have the greatest synthesis rates of proteins?
GI tract, liver.
What does ADMA stand for?
Assymetric dimethylarginine
What does ADMA do?
Inhibits nitric oxide synthase.
What are the effects of excess ADMA?
Hypertension due to lack of NO to induce vasodilation.
State the reaction of dopamine hydroxylase - its location, substrate, product and cofactors
Converts dopamine to norepinephrine in the adrenal medulla and brain. Requires Copper (as Cu++) and vitamin C.
How might strongly elevated serine with low glycine on a plasma amino acid profile correlate to poor growth, maldigestion, impaired cognition or excessive fatigue?
Normally, gly and ser can be easily interconverted and tend to move up or down together on the profile. If not, the glycine cleavage system may be suspected - possible genetic or toxicant interruption of that system would prevent degradation. Can cause non-ketotic hyperglycinemia. Since the glycine cleavage system is a major source of single carbons for THF pathways, multiple biosynthetic and methylation defects may result.
What nutrients are required for the conversion of glycine to serine?
B6, Mn, folate
How are free-form amino acid products typically customized?
Low levels of amino acids in profiles govern amounts added for each. Usual dosing is a rounded teaspoon twice daily.
Corrections of what amino acid insufficiencies are found to be helpful in anxiety? Why?
If related to imbalanced brain neurotransmitter function may respond to amino acids that act directly as receptor agonists (Lys, Gly, Tau) or serve as precursors to neurotransmitters (Phe).
What amino acid imbalance is indicative of ornithin transcarbamoylase deficiency?
The greatest elevation is usually ornithine (substrate).
Into what categories are the fatty acids typically placed on laboratory reports?
Categorized according to chain length within each greater category or desaturation leel or PUFA omega double bond position.
What fatty acid is part of the structure of the most active endocannabinoids?
Arachidonic acid
What essential fatty acid tends to become persistently low in patients using fish oil supplements?
Arachidonic acid. Superior binding of the n-3 FA to desaturase enzymes tends to suppress the desaturation of linoleic and GLA to form AA.
The composition of which lipoprotein is largely revealed in measurements of both serum triglycerides and plasma fatty acids?
Largely LDL particles, since usually done in a fasting state.
Which foods are particularly rich in linoleic acid?
(In order of abundance) evening primrose , safflower, grape seed, sunflower and hemp.
Which cellular organelle other than mitochondria is required for VLCFA degradation? What clinical consequence is common?
Peroxisomes. VLCFA intermediates cannot be processed in mitochondria, so has to be transported into peroxisomes in order to generate DHA. Thus infants born to women deficient in DHA take a long time to develop their own DHA levels from dietary precursors.
What essential nutrient other than PUFAs is required to stimulate peroxisome proliferation?
Simultaneous binding of a PUFA and vitamin A (as 9-cis-retinoic acid) is required to activate PPAR. Deficiency of Vit A or PUFAs may impact fundamental cellular response to energetic or immunological stressors.
Would the symptoms associated with linoleic acid deficiency best be described as diverse or specific? Why?
Highly diverse. Central role in 2 processes that broadly impact cellular function: 1. cell membrane properties that affect membrane-bound protein complexes and receptors in all tissues. 2. formation of the dominant eicosanoid precursors, GLA and AA.
What fatty acid profile imbalance tends to exaggerate inflammatory responses?
Low levels of n-3 PUFAs (especially EPA) along with elevated AA
What essential fatty acid is likely to be found low in patients on aggressive, long-term omega-3 therapy?
Arachidonic acid
What clinical syndrome is indicated by finding a 'greater than' sign in the family of saturated fatty acids? i.e. high palmitic and stearic dominating over the family of SFAs. Why?
Metabolic syndrome aka syndrome X, prediabetes, hyperinsulinemia, dysinsulinemia. Insulin stimulates endogenous FA synthesis.
Adrenoleukodystrophy is associated with what pattern of fatty acid abnormalities?
Etiology of adrenoleukodystrophy is lack of peroxisome activity required for oxidation and clearance of VLCFA. Those FA accumulate massively, producing chronically progressive neuropathic symptoms.
What element cofactor is required by the desaturase enzymes?
Zn++
Compare the LCFA profile of borage vs evening primrose oil.
Borage contains GLA only. Evening primrose contains less GLA but is high in LA.
What fatty acids are recommended for hypertriglyceridemia
Fish oil. Decrease CHO intake.
What primary organic acid abnormalities occur in carnitine deficiency?
Elevated adipate, suberate and ethylmalonate
What patterns of abnormalities discriminate mitochondrial inefficiency from ammonia challenge as a cause of citric acid elevation?
Ascribe high levels of citrate, aconitate and isocitrate to ammonia when (a) only citrate, aconitate and isocitrate are found high, or (b) orotate is concurrently elevated.
What does NDMA stand for?
N-methyl-D-aspartic acid (a class of ionotropic glutamatergic neuron receptors).
Why are NMDA receptors important?
It is those receptors that are agonized by quinolinic acid and potentiated by picolinic acid resulting in potential glutamate toxicity in neurons.
What urinary organic acid elevation may justify specifically aggressive vitamin C supplementation?
Elevated p-hydroxyphenyllactic acid (marker for tumor growth) and the concomitant elevated cell division rate stimulation that tends to produce systemic oxidative stress.
How does glutathione biosynthesis (from Hcys) relate to the organic acid marker 8-OHdG?
Failure of the reciprocal regulation between transmethylation and transulfuration of Hcys can impair up-regulation of hepatic glutathione synthesis as the major response to oxidative stress, leading to exacerbated and prolonged cellular (esp. mitochondrial) damage from oxidant effects. 8OHdG is a marker of DNA damage due to oxidative stress.
Why is supplementation with glucarate salts NOT indicated by abnormalities in urinary glucarate?
Urinary glucarate is a marker for increased hepatic detoxification activity (it is a by-product of pathways leading to glucuronic acid formation). Oral glucarate salts decrease enterohepatic recirculation of carcinogens. See p.365
What is the implication of LOW homocysteine for the likelihood of finding elevated alpha-hydroxybutyrate (AHB)?
Elevated AHB indicates up-regulated hepatic glutathione synthesis, and that process demands flow of HCys into L-Cys to form glutathione. Thus low plasma HCys can signal a late-stage of chronic glutathione depletion where total body sulfure amino acid availability is failing to keep up with demand.
Explain how elevated benzoate can be a marker of either impaired detoxification or intestinal bacterial overgrowth. What other biomarker can help differentiate the two scenarios?
Elevated benzoate can be due to either (a) failure of hepatic clearance by hippurate formation (impaired detox) or (b) bacterial action on dietary polyphenols releasing benzoate (which exceeds liver clearance capacity). Elevated hippurate indicates scenario (a), low/normal hippurate indicates scenario (b).
What is the difference between arabinitol and arabinose? Which one is a urinary biomarker and for what?
Arabinose is a 5-C sugar found in grapes and other fruits/veg. It is a substrate for growth of some bacteria. Arabinitol is the corresponding sugar alcohol that is formed by conversion of dietary CHO by intestinal Candida species. It serves as a biomarker for overgrowth, including severe, invasive cadidiasis.
Which organic acids are elevated in maple syrup urine disease? Why?
Branched-chain keto acids (a-ketoisocaproate, a-ketoisovalerate, and a-keto-b-methylisovalerate. This is due to genetic abnormalities reducing the activity of branched-keto acid dehydrogenase.
What supplements may assist some forms of maple syrup urine disease? Why do not all forms respond?
Cofactors B1, B2, B3, B5, lipoic acid may help. But if the SNPs relate to severe alterationsin the enzyme binding sites for the cofactors, supplementation may have no effect.
Which organic acids re used to discriminate potential vitamin deficiencies causing homocysteine elevation?
FIGLU (for folate) and MMA (for B12).
Are you having fun yet? Yes or No?
Cheer up!! You're going to do great...!
Explain how products of the kynurenin pathway can provide evidene of micronutrient status and CNS pertubations.
B6 impairs this pathway - deficiency elevates primarily xanthurenate, but also kynurenic acid/kynurenate. In a B6 sufficient state, Inflammation activates this pathway in the brain leading to products quinolinate and picolinate (since brain does not have enzymes to complete the conversion to nicotinic acid).
Explain how glycine insufficiency causes elevated pyroglutamate?
Glycine is required in the kidney to sustain reformation of glutathione. Lack of glycine is one reason why the critical gamma-glytamyl pathway is truncated prior to executing the GSH reconstruction, causing release of the glutamic acid moiety as pyroglutamate.
Why might an interruption in the TCA cycle at any single step NOT always cause low level of products and high levels of preceeding substrates?
The mitochondrial membrane is selectively permeable, regulated by transport proteins. Thus specific TCA cycle intermediates can easily leave and their levels do not become elevated.
How can smoking be connected to glucarate levels?
Smoking can increase urinary glucarate levels, indicating activity of hepatic detoxification.
What does a 6-month progressive lowering of urinary sulfate with persistent elevation of pyroglutamate imply about a patients' prognosis? What specific nutrient interventions are indicated?
Progressively lowering sulfate indicates chronic toxicant challenge/oxidative stress. Pyroglutamate elevation indicates that glutathione losses may be a contributing factor. Glutathione support is indicated via GSH or precursors (Cys, Met, Gly, and related amino acids. Tau, Ser, Thr may be helpful in restring GSH status.
What three peptides make up glutathione?
Cys - Gly - Glu
What is a metabolic rationale for the high incidence of hypochlorhydria?
Decline in stomach acid output with age, likely associated with underlying metabolic changes tied to nutrient insufficiencies and toxic effects.
What nutrient insufficiencies can lead to impaired HCl output in the stomach?
Zinc, biotin (for protein synthesis suport), B complex, iron, CoQ10 for mitochondrial activity.
What nutrient insufficiencies are generally caused by low HCl?
Protein and major/trace elements.
What patterns of abnormalities in stool chemistries are found in conditions of low stomach acid?
Abnormal commensal bacterial distributions.
What patterns of abnormalities in stool chemistries are found in conditions of low pancreatic enzymes?
Decreased digestion of dietary components (esp protein) resulting instimulation of certain bacteria that metabolize amino acids.
What patterns of abnormalities in stool chemistries are found in conditions of impaired small bowel absorption?
Decreased absorption of dietary components stimulates microbe growth due to availability of growth substrate.
What are the different clinical values of testing for leaky gut with the lactulose-mannitol challenge and IgG4 testing?
Lactulose-mannitol (lactulose is normally poorly-absorbed, mannitols is normally well-absorbed) evaluates intestinal permeability. However, it does not also answer the question about whether macromolecules from food are regularly permeating the intestinal barrier and producing immunological responses - serum IgG4 would do that.
How does complement cascade activation explain differences between clinical interpretations of elevated serum IgG1 and IgG4 class antibodies to food antigens?
IgG1 class antibodies are those that are first produced in reaction to food components penetrating intestinal barriers. IgG1-food complexes are degraded by complement systems. However, complement proteins do not recognize IgG4-food complexes, so they remain in circulation much longer (days to weeks).
What intestinal bacterial genus is suspected to be prevalent in the patient with high p-hydroxyphenylacetate, 8-OHdG, orotate and glucarate?
Ammonuria indicated by elevated orotate suggests the bacteria genera capable of high ammonia production, including clostridia, enterobacter and Bacillus.
Below the threshold dose, how do responses predicted by the hormesis model differ from those derived from the threshold model?
Threshold models presume nil response below the threshold for positive responses. Hormesis models predicts (or allows) negative responses in the regions below the threshold for positive responses.
How might the hormesis model explain lower incidence of breast cancer in women who smoke tobacco?
Smoking below the threshold for increasing cancer incidence might produce lower risk via mechanisms such as induction of hepatic detoxification systems that lower total body estrogen exposure.
Why does oral DMSA cause dramatic increases in urinary elemental levels in patients with high body burdens of toxic elements?
When a patient with a high body burden of a toxic element starts DMSA therapy, loses on a given day may be offset by release of the element from deep stores such as bone over a time interval longer than the urine collection during therapy. The DMSA can act to stimulate mobilization of old pools with slow turnover.
What compound reacts with acetaminophen to initiate mercaptan formation?
Glutathione. This explains the potential for uncontrolled oxidative stress and organ failure due to overdosing of drugs like acetaminophen that produce high demand for hepatic glutathione conjugation.
What is your interpretation of an elevated plasma Cys/Sulfate ratio and low urinary sulfate, together with high urinary mercury, and high 8OHdG?
Lack of sulfur compound precursors is hampering sulfoxidation and probably impairing maintainance of glutathione reserves. Causative factor is most likely mercury, which is causing DNA damage.
What micronutrient is specifically likely to assist the patient with elevated benzoate
Glycine for glycine conjugation (phase II reaction). The reaction also requires Coenzyme A, so high rates of reaction can drain pantothenic acid reserves. So pantothenate would also help.
Why does mercury toxicity produce elevations of precoproporphyrin, pentacarboxyporphyrin and coproporphyrin (total)?
Urophorphyrin decarboxylase catalyzes a series of 4 decarboxylation reactions. After each step the product must dissociate from the enzyme and re-associate in a new confirmation that places the next carboxyl group at the active site. Mercury binds strongly to the enzyme such that the product of the third decarboxylation (pentacarboxyporphyrinogen) has difficulty reentering the site, causing it to accumulate and spill into urine. The prior step also backs up, causing hexacarboxyporphyrinogen to spill also. Meanwhile, the excess pentacarboxyporphyrinogen is converted to precoproporphyrin.
What are common symptoms of a pathological detoxifier? What specific observation indicates phase II detox difficulty from these options: elevated bilirubin, or high caffeine clearance?
Symptom-free until biotransformation systems are stressed; then noticeable symptoms appear. Elevated bilirubin indicates difficulty with glucuronidation.
Why is excess phase I activity with relative phase II deficiency a cause for concern?
Phase I products tend to become even more toxic than their precursors.
What trace elements are involved in protecting against oxidative stress?
Zinc and copper in superoxide dismutase (cytosolic). Manganese in superoxide dismutase (mitochondrial). Selenium in glutathione peroxidase.
What micronutrients are needed for the regeneration of GSH?
Selenium, B2 (as FAD) and B3 (as NADPH).
What is the role of vitamins A, C, E and beta-carotene in oxy-stress?
Removing oxygen radicals.
Why should botanical sources of antioxidants, such as Panax ginseng or Ginkgo biloba, be considered rather than individual antioxidant micronutrient supplementation?
Because balanced intake of all of the antioxidants is superior to individual supplementation because of the demonstrated codependence.
What factor released during sleep adds strong protection against oxidative stress?
Melatonin. It's roughly twice as effective as vitamin E for protection against the peroxyl radical.
Why is it unusual to find elevated levels of lipid peroxides when fat-soluble nutrients are in their upper ranges? What other nutrients might therefore need evaluation?
Good levels of fat-soluble vitamins should indicate protection against oxidative stress especially in cell membranes, where oxidative stress without adequate protection would lead to elevated lipid peroxides. It would be important to evaluate membrane FA components, since it may be that levels of easily-oxidized PUFAs are elevated.
Consider the similarities between hormones and microRNAs.
Did you consider them? Basically, just understand that the body uses a full and diverse array of cell regulators to achieve homeostasis in spite of dramatic fluctuations in daily habits and circumstances.
What is the danger of therapeutic use of hormones?
There is a danger of overuse because they are part of a delicate balancing system.
What are the effects of excess growth hormone?
Gigantism, acromegaly, other malformations.
What are the effects of deficient growth hormone?
Depends on age. In young children - growth failure. In adults - metabolic syndrome, osteoporosis, muscle wasting, impaired quality of life, increased cardiovascular events.
What are the effects of excess thyroxine?
Palpitations, heat intolerance, nervousness, insomnia, breathlessness, increased bowel movements, light/absent menstrual periods, fatigue, fast heart rate, trembling hands, weight loss, muscle weakness, warm/moist skin, hair loss, staring gaze.
What are the effects of deficient thyroxine?
Fatigue, weakness, weight gain, hair loss, cold intolerance, muscle cramps, constipation, depression, irritability, memory loss, abnormal menstruation, decreased libido, pale/dry skin, coarse/dry hair, puffy face, hoarse voice, elevated blood cholesterol.
What are the indications of excess DHEA?
May be an early indicator of depression.
What are the effects of deficient DHEA?
Low levels of sex hormones testosterone and estrogen. DHEA also has immune-modulating effects and prevents stress-induced damage to the hippocampus, as in Alzheimer's Disease.
What are the effects of excess cortisol?
Blocks insulin action (so increased blood sugar), suppresses immune system, increased protein breakdown. May cause greater urinary losses of B-vitamins, lowered mineral status and reuced absorption of calcium, and a greater need for vitamins C and E.
What condition is associated with low cortisol?
Adrenal insufficiency, showing lowest cortisol in morning.
What condition is associated with excess cortisol output, especially in the evening, when cortisol should be naturally falling?
Cushing's syndrome.
How is sIgA linked with chronic stress?
Decreased sIgA in chronic stress.
What are the possible effects of elevated estradiol.
May simulate immune response. Increased breast cancer risk. Increased prostate cancer growth. SYmptoms include anxiety, difficulty sleeping, irritability. Breast fibroids or cysts.
What are the possible effects of deficient estrogen?
Breast cells will not mature properly. Menopausal symptoms.
What are the possible effects of excess progesterone?
Increased free estrogen (via increased sulfatase activity), urinary incontinence, decreased coordination, slowed reflexes, impaired memory and reasoning skills, increased risk for diabetes. Possibly migraines. Possibly chronic fatigue.
What vitamin has been shown to increase levels of progesterone?
Vitamin C
What are the effects of low testosterone?
High cortisol, possibly metabolic syndrome, T2DM and cardiovascular disease.
What are the effects of high testosterone
Increased risk for growth of prostate cancer cells.
What advantage may be derived from the use of a patient's genomic data when choosing drug therapies?
Drugs are metabolized/cleared via detoxification enzymes. Thus SNPs in phase I CYP enzymes or phase II enzymes may alter the patient's clearance rates of that drug.
What information does the term C677T convey about a SNP?
Specifies location (base number 677) and nucleotide replacement (cytosine to thymine) that is present.
What proportion of drugs are metabolized by the cytochromes uniquely required for forming 16a-hydroxyesterone?
The CYP3A4 and CYP2E variants required for 16a-hydroxyestrone formation are present at 35% and 4% respectively.
What steps in the overall process from DNA expression to cellular outcome are potentially impacted by environmental factors?
All steps including DNA transcription, RNA translation and protein function are potentially impacted by environmental factors.

Finding elevated urinary alpha-ketoisocaproate and alpha-ketoisovalerate is an indication of what essential nutrient deficiency?




Coenzyme Q10


Vitamin B1


Vitamin B6


Vitamin D

Vitamin B1

When serum lipid peroxides are elevated even though all serum antioxidant vitamins are in their upper normal ranges, what other abnormality is likely to be present?




High vitamin D


High polyunsaturated fatty acids in plasma


Low polyunsaturated fatty acids in plasma


Low biotin

High polyunsaturated fatty acids in plasma

Which compound is measured as a laboratory test for vitamin K deficiency?




Sepiapterin


Undercarboxylated osteocalcin


7-Dehydrocholesterol


Dehydroascorbic acid

Undercarboxylated osteocalcin

Assessment of vitamin D deficiency is done by measuring serum levels of what compound?




1,25-Dihydroxyvitamin D


Calcitriol


25-Hydroxyvitamin D


Previtamin D3

25-Hydroxyvitamin D

A patient can have normal serum vitamin B12, but still show elevated urinary methylmalonate because




*Methylmalonate causes anemia from folic acid deficiency.


*The folate trap prevents proper methylation.


*Methylmalonate metabolism requires intra-cellular activity of vitamin B12.


*Vitamin B12 promotes the formation of methylmalonate.

Methylmalonate metabolism requires intra-cellular activity of vitamin B12.

Which of the following is NOT a folate deficiency sign?




Plasma homocysteine elevation


Neutrophyl hypersegmentation


Urinary xanthurenic acid elevation


Urinary formiminoglutamate elevation

Urinary xanthurenic acid elevation

Which vitamin insufficiencies are indicated by elevated branched chain keto acids in urine?




Antioxidants


Ascorbates


B-complex


Cholecalciferols

B-Complex

Why is it incorrect to speak of a “folic acid” deficiency?




Folic acid is not related to tetrahydrofolate


Folic acid is not an essential nutrient


Human tissues can synthesize folic acid


Folic acid is highly toxic

Folic acid is not an essential nutrient

Vitamin B6 deficiency causes elevated homocysteine by what mechanism?




*Accelerating the conversion of methionine to homocysteine


*Blocking the transfer of methyl groups to THF


*Impairing the conversion of homocysteine to cysteine


*Reducing the active form of vitamin B12

Impairing the conversion of homocysteine to cysteine

What does the abbreviation BH4 represent?




A part of vitamin B12 structure


A catabolic product of vitamin B6


Tetrahydrobiopterin


A test for B-complex vitamin deficiency

Tetrahydrobiopterin

Which of the following is NOT useful for assessing iron status?




Transferrin saturation


Hair iron concentration


Serum ferritin


Total iron binding capacity

Hair iron concentration

A patient with chronic negative calcium balance is expected to have elevated calcium in which specimen type?




Erythrocytes


Whole blood


Unchallenged 24 hr urine


Head hair

Head hair

What organ failure most directly causes multiple low essential trace elements to be found in blood or urine?




Stomach


Kidney


Liver


Pancreas

Stomach

A DMSA provocation test would usually be done to assess what problem?




Trace element loss due to renal retention deficit Toxic element exposure


Hypothyroidism due to iodine malabsorption


Bone loss due to calcium deficiency

Toxic element exposure

When very low erythrocyte magnesium is found, the patient is likely to have what other type of insufficiency?




Selenium


Iron


Glutathione


Vitamin C

Glutathione

Which of the following is not considered to be a highly toxic element?




Arsenic


Mercury


Boron


Lead

Boron

Which of the following is a good test for copper excess?




RBC Cu


Urinary copper


Low serum copper to ceruloplasmin ratio


Urinary HVA/VMA ratio

Urinary Copper

The action of what hormone is reduced in chromium deficiency?




Insulin


Testosterone


Thyroxine


Glucagon

Insulin

Why does direct testing of calcium in body fluids fail to reveal nutritional status of calcium?




*Other elements interfere with the measurement of calcium in body fluids.


*Calcium levels in body fluids change too rapidly to allow interpretation of calcium balance. *Strong mechanisms assure constant ionic calcium levels even in calcium deficiency.


*Calcium is present at levels too low to detect in body fluids.

Strong mechanisms assure constant ionic calcium levels even in calcium deficiency.

What element has been shown to protect from the toxic effects of mercury?




Copper


Selenium


Zinc


Magnesium

Selenium

A pattern of elevated essential amino acids is an early sign of deficiency of what vitamin?




C


A


B6


B12

B6

Which medical condition is often found in patients with elevated plasma asymmetric dimethylarginine?




Food allergies


Maldigestion


Hypertension


Chronic fatigue

Hypertension

What metabolic process creates the largest demand for amino acids?




Hepatic detoxification reactions


Protein synthesis


Hydrochloric acid production


Neurotransmitter synthesis

Protein Synthesis

What effect does delayed specimen transport have on relative levels of glutamate and glutamine?




The levels are stable for at least one week.


Glutamine is consumed by enzymes in plasma


Glutamate decreases due to changes in pH


Glutamine is slowly hydrolyzed to glutamate

Glutamine is slowly hydrolyzed to glutamate



Which amino acid, when administered as a challenge for testing status of a vitamin, helps to alleviate one of the effects of deficiency of the vitamin?




Tryptophan


Phenylalanine


Histidine


Isoleucine

Histidine

Which amino acid is converted into a neurotransmitter by two sequential hydroxylation reactions requiring tetrahydrobiopterin as a cofactor?




Glutamic Acid


Valine


Tryptophan


Phenylalanine

Phenylalanine

Which amino acid is a substrate for competing reactions that lead to either a compound that supplies a methyl group or to a compound that supplies protection from oxidative stress?




Taurine


Proline


Asparagine


Homocysteine

Homocysteine

What is the principal metabolic outcome of the glycine cleavage system?




*Generation of 5-10-methylene THF


*Regeneration of tetrahydrobiopterin


*Conversion of glycine to an important neurotransmitter


*Initiation of the pathway that leads to heme formation

Generation of 5-10-methylene THF

If a plasma amino acid profile shows low levels of four essential amino acids and normal levels of the others what intervention is generally indicated?




*A high fiber diet to reduce intestinal transit time


*A combination of antioxidants and the trace elements Zn, Cu and Mn


*Supplementation of the amino acids that are low at about twice their RDA levels


*A customized mixture of all essential amino acids

A customized mixture of all essential amino acids

The principal advantage of free form amino acid supplements over purified protein products is




*Lower risk of producing nitrogen overload


*Greater penetration into distal regions of the gut lumen


*More rapid delivery of amino acids into peripheral blood


*Lower risk of gall bladder attacks due to release of cholegogues

More rapid delivery of amino acids into peripheral blood

Which abnormality pattern, when found on a plasma fatty acid report, indicates that a patient is in general essential fatty acid deficiency?




Elevated stearic/oleic ratio


Low ALA, EPA, DHA and high stearic acid


Low Mead and palmitic acids


Low omega 3 and omega 6 with elevated Mead acid

Low omega 3 and omega 6 with elevated Mead acid

Which abnormality pattern, when found on a plasma fatty acid report, indicates that a patient is in omega-3 fatty acid deficiency?




Low stearic/oleic ratio


Low ALA and EPA


Low LA, DGLA and AA


High palmitic/palmitoleic ratio

Low ALA and EPA

Which abnormality pattern, when found on a plasma fatty acid report, suggests that a patient may be hypertriglyceridemic?




*An elevated triene/tetraene ratio


*Low levels for all omega-3 and omega-6 fatty acids


*All saturated and monounsaturated fatty acids found in their 4th or 5th quintiles


*A low triene/tetraene ratio

All saturated and monounsaturated fatty acids found in their 4th or 5th quintiles

Which abnormality pattern, when found on a plasma fatty acid report, indicates that a patient is exhibiting the metabolic syndrome?




*Generally low monounsaturated fatty acids and a high LA/GLA ratio


*Generally high monounsaturated all fatty acids with chain lengths of less than 20 carbons


*A “greater than” sign in quintile positions of the saturated fatty acids when they are arranged according to chain length


*A “less than” sign in the quintile positions of the saturated fatty acids when they are arranged according to chain length

A “greater than” sign in quintile positions of the saturated fatty acids when they are arranged according to chain length

Which abnormality pattern, when found on a plasma fatty acid report, indicates a patient has adrenoleukodystrophy?




*Greatly elevated lignoceric and hexacosanoic acids with normal levels of other saturated fatty acids


*Greatly elevated capric and lauric acids with normal levels of other saturated fatty acids


*Very low levels of monounsaturated fatty acids with gradually increasing levels of saturated fatty acids as chain length decreases.


*Simultaneous very high Mead, palmitoleic, and vaccenic acids with normal levels of myristoleic and erucic acids

Greatly elevated capric and lauric acids with normal levels of other saturated fatty acids

Finding multiple odd-chain fatty acids in erythrocytes means that there is some process causing elevated levels of which compound?




Stearate


Fumarate


Erucate


Propionate

Propionate

Which fatty acid source is appropriate for treatment of a patient with ALA and EPA in their upper quintiles and with LA and GLA in their first deciles?




Flax oil


Primrose oil


Fish oil


Corn oil

Primrose oil

What is the common name for the fatty acid written as 20:4n6?




Arachidonic acid


GLA


EPA


Linoleic acid

Arachidonic acid

What cellular organelles other than mitochondria are required for VLCFA degradation?




Peroxisomes


Smooth endoplasmic reticulum


Rough endoplasmic reticulum


Liposomes

Peroxisomes

Which vitamin is necessary for stimulation of PPAR?




Riboflavin


Vitamin A


Niacin


Folic acid

Vitamin A

Which of the following is a urinary organic acid that becomes elevated as a direct result of carnitine deficiency?




Adipate


Citrate


Orotate


Kynurenate

Adipate

Which of the following is a urinary organic acid that becomes elevated as a result of Coenzyme Q10 deficiency?




Vanilmandelate


Succinate


Pyroglutamate


D-Lactate

Succinate

Which of the following is a urinary organic acid that becomes elevated as a direct result of thiamin deficiency?




Phenylpropionate


Glucarate


Alpha-ketoisocaproate


Formiminoglutamate

Alpha-ketoisocaproate

Which of the following is a urinary organic acid that becomes elevated as a direct result of vitamin B6 deficiency?




Beta-hydroxyisovalerate


Methylmalonate


Fumarate


Xanthurenate

Xanthurenate

Which of the following is a urinary organic acid that becomes elevated as a direct result of biotin deficiency?




Alpha Ketoglutarate


Beta-hydroxyisovalerate


Alpha keto-B-methylvalerate


Alpha ketoisovalerate

Beta-hydroxyisovalerate

Which of the following is a urinary organic acid that becomes elevated as a direct result of folic acid deficiency?




Formiminoglutamate


Hydroxymethylglutarate


Ethylmalonate


Homogentisate

Formiminoglutamate

Elevation of which of the following urinary organic acids indicates that a patient has increased turnover of epinephrine?




Homovanillate


Vanilmandelate


Kynurenate


Hippurate

Vanilmandelate

Elevation of which of the following urinary organic acids indicates that a patient has increased turnover of serotonin?




2-Methylhippurate


5-Hydroxyindoleacetate


3,4-Dihydroxyphenylpropionate


8-Hydroxy-2’-deoxyguanosine

5-Hydroxyindoleacetate

Elevation of which of the following urinary organic acids is produced in a patient with thiamin deficiency that slows the action of the branched-chain keto acid dehydrogenase complex?




Alpha-keto-beta-methylvalerate


Alpha-hydroxybutyrate


Alpha


8-Hydroxy-2’-deoxyguanosine

Alpha-keto-beta-methylvalerate

Which of the following is a urinary organic acid that becomes elevated in a patient due to massive intestinal overgrowth of Lactobacillus acidophillus?




D-Lactate


D-Arabinitol


L-Lactate


D-Glucarate

D-Lactate

Which of the following is the most common reason for finding elevated benzoic acid in urine?




*The liver is converting more toluene into benzoic acid.


*Hepatic coenzyme A levels are increasing.


*Pantothenic acid supplementation has been increased


*Hepatic glycine conjugation capacity has been exceeded.

Hepatic glycine conjugation capacity has been exceeded

Why would a high protein diet be ill-advised for the patient whose laboratory report indicates a pathological detoxifier pattern?




*It would exacerbate the effects of low Phase II detoxification capacity


*Phase I detoxification needs to be stimulated


*Methylation pathways would be overloaded


*Pathological detoxifiers have difficulty with ammonia clearance

It would exacerbate the effects of low Phase II detoxification capacity

Which type of organotoxin is famous for originating from soft plastic products?




Phthalates


Organophosphates


Volatile solvents


PCBs

Phthalates

What are urinary products of glutathione conjugation called?




Gamma-glutamyl conjugates


Glycine conjugates


Sulfated esters


Mercaptans

Mercaptans

Ammonia detoxification is not described by Phase I and Phase II reactions because




*It does not require oxidation and conjugation for clearance.


*It requires only oxidation in order to be cleared.


*It is conjugated before it is oxidized for its major pathway of detoxification.


*Ammonia leaves the body primarily as exhaled gases.

It does not require oxidation and conjugation for clearance

How does dietary fiber help control total estrogen exposure in premenopausal women?




*Stimulation of cytochrome P450 hydroxylation *Reduction of enterohepatic estrogen circulation


*Reduction of ovarian estrogen synthesis


*Stimulation if intestinal lipid absorption

Reduction of enterohepatic estrogen circulation

What urinary porphyrin becomes uniquely elevated in urine due to mercury toxicity?




Precoproporphyrin


Uroporphyrin I & III


Coproporphyrin


Protoporphyrin

Precoproporphyrin

Which of the following toxicants is considered to be iatrogenic?




5-Methylchrysene


Acetaminophen


Naphthalene


D-Lactic acid

Acetaminophen

How does the stimulation of hepatic cytochrome P450 activity by compounds in cigarette smoke illustrate the hormesis model of toxicant effects?




*All compounds in cigarette smoke are toxic at all concentrations


*Very low doses of a toxic compound can have favorable effects


*Cigarette smoke is only toxic under certain dietary conditions


*Cytochrome P450 creates non-toxic compounds from most compounds in cigarette smoke

Very low doses of a toxic compound can have favorable effects

Why is oral challenging with DMSA used prior to toxic element testing of urine?




*To establish a baseline level before test specimen collection


*To normalize for hemoglobin in urine


*To demonstrate metallothionein loading status


*To increase instrumental sensitivity for mass spectrometric assay

To demonstrate metallothionein loading status

What information is conveyed by this figure on a laboratory SNP profile report?




*One allele of the relevant gene was negative and the other one was positive for the relevant SNP.


*The patient has been found to be homozygous for the relevant SNP that was investigated.


*The patient has a 50% chance of manifesting symptoms due to a positive SNP finding.


*A SNP was found in one gene that is offset by an opposing SNP in another gene.

One allele of the relevant gene was negative and the other one was positive for the relevant SNP.

What kind of clinically relevant information is found at the web site named OMMBID?




*OMMBID is a database of SNPs.


*Anatomic pathology features of chronic diseases are illustrated.


*It is a site where taxonomic features are described.


*Metabolic defects are described for inherited diseases.

Metabolic defects are described for inherited diseases

What advantage may be derived from the use of a patient’s genomic data when choosing drug therapies?




*Patients with certain genomic features are referred for naturopathic care.


*Drugs can be targeted to change gene expression.


*Specific SNPs can be corrected by proper drug selection.


*Dosages may be adjusted according to SNPs that affect their metabolism.

Dosages may be adjusted according to SNPs that affect their metabolism.

The designation (A856G) conveys what information?




*At position 856 in the expressed protein glutamic acid is present instead of the normal arginine residue.


*At base position 856 in the related gene there is a single nucleotide polymorphism due to replacement of adenosine by guanosine.


*The wild type gene contains the A-G pair at position 856.


*A total genome analysis found 856 A-G SNP alterations among the 23 human chromosomes

At base position 856 in the related gene there is a single nucleotide polymorphism due to replacement of adenosine by guanosine.

The figure shown illustrates what aspect of genomics in drug metabolism?




*The designations such as “1A1” describe the gene positions and the percentage values show how many people have defects of that type.


*The figure shows how many people have difficulty clearing 10 different types of drugs due to genetic defects in the cytochrome P450 enzyme of the detoxification system.


*Each sector represents the relative incidence of SNPs for the various enzymes.


*No specific genetic information is shown, but rather the figure illustrates the diversity of cytochrome P450 isozymes, each of which may be affected by SNPs in each individual.

No specific genetic information is shown, but rather the figure illustrates the diversity of cytochrome P450 isozymes, each of which may be affected by SNPs in each individual.

Which of the following steps in gene expression can be altered by environmental factors?




DNA transcription


RNA translation


Post-translational protein alterations


All of the above are correct responses

All of the above are correct responses

If a patient is found to be homozygous for SNP that causes lowered activity of the enzyme required for conversion of dopamine to epinephrine, what laboratory report abnormality would show metabolic confirmation of the effect?




Low urinary vanilmandelic acid


High urinary vanilmandelic acid


High urinary 5-hydroxyindoleacetic acid


Low urinary pyroglutamic acid

Low urinary vanilmandelic acid

A genetic defect in what metabolic area is suggested by a specific pattern in the laboratory report shown here?




*Detoxification systems Phase II glycine conjugation


*Thyroid conversion of indican to thyroxin


*Vitamin B12 utilizing enzymes for converting phenylpropionate to succinate


*Gastric enzymes that degrade tricarboxylic acids

Detoxification systems Phase II glycine conjugation

Which response describes the level at which microRNAs act to affect processes like the uptake of micronutrients such as iron?



*Changing protein structures by modifying amino acid side chains


*Shifting gene products due to the presence of SNPs


*Alteration of gene expression rates


*Preventing the formation of ribosomal RNA

Changing protein structures by modifying amino acid side chains

How is an enzyme’s activity altered by the presence of a homozygous SNP in the genes that express that enzyme?




*The rate of the catalyzed reaction is decreased.


*There is no change in the rate of the catalyzed reaction.


*The rate of the catalyzed reaction is increased.


*Any one of 3 of the above responses may apply to a given SNP.

Any one of 3 of the above responses may apply to a given SNP

Which of the following agents acts to protect enzymes inside of the mitochondria from oxidative damage?




Zinc-copper superoxide dismutase


Manganese superoxide dismutase


Ceruloplasmin


Catalase

Manganese superoxide dismutase

What amino acid is unusually high inside erythrocytes to afford oxidative stress protection?




Taurine


Threonine


Thyroxin


Tyrosine

Taurine

Which vitamin sits near the center of the cellular redox potential spectrum?




Vitamin A


Pantothenic acid


Vitamin D


Vitamin C

Vitamin C

Accumulation of which compound tends to produce reductive stress?




BH4


NADH


NAD+


GSH

NADH

Which compound is sometimes used as a biomarker of total body protein oxidative damage?




DNA strand breaks


Pyroglutamate


Uric acid


Nitrotyrosine

Nitrotyrosine

Match the laboratory markers with their category of oxidative stress damage


Isoprostanes, Methionine sulfoxide, 8-Hydroxy-2'-deoxyguanosine, 3-Nitrotyrosine




Carbohydrate damage, Lipid damage, Protein damage, DNA damage

Isoprostanes - Lipid damage


Methionine sulfoxide - Protein damage


8-Hydroxy-2'-deoxyguanosine - DNA damage



In a patient with multiple signs of oxidative stress, physiological forms of which two micronutrients are needed because they act in tandem directly upon glutathione to achieve the recycling of the oxidized to the reduced form?




lysine and taurine


EPA and DHEA


folate and vitamin B12


lipoate and nicotinamide

Lipoate and nicotinamide

What factor released during sleep adds strong protection against oxidative stress?




Melatonin


Prostaglandin E2


Serotonin


IGF

Melatonin

What antioxidant is specifically indicated to be under stress, leading to reduced antioxidant stress response capacity when a patient is found to have elevated pyroglutamate and alpha-hydroxybutyrate?




Catalase


Trace elements


Tocopherols


Glutathione

Glutathione

Which response shows the three trace elements that are required for the action of superoxide dismutase enzymes?




Fe, Mg, Zn


Co, Mo, Zn


Zn, Ca, Se


Cu, Zn, Mn

Cu, Zn, Mn

Production of which of the following cell regulators is directly affected by deficiency of iodine?




Nitric oxide


Serotonin


Thyroxin


Corticosteroids

Thyroxin

Production of which of the following cell regulators is directly affected by deficiency of tryptophan?




Nitric oxide


Thyroxin


Serotonin


Corticosteroids

Serotonin

Production of which of the following cell regulators is directly affected by deficiency of arginine?




Nitric oxide


Thyroxin


Serotonin


Corticosteroids

Nitric oxide

Production of which of the following cell regulators is directly affected by excessive consumption of broccoli?




Thyroxin


Corticosteroids


Serotonin


Nitric oxide

Thyroxine

Which of the following is a hormone that is NOT derived from cholesterol?




Estrone


Testosterone


Cortisol


Norepinephrine

Norepinephrine

Which of the following test results is a marker for chronic stress response?




Low insulin


High estradiol


High thyroxin


Low sIgA

Low sIgA

What hormonal abnormality would be suspected in a patient with elevated serum triglycerides, elevated serum LDL cholesterol, obesity and non-alcoholic live disease?




Low cortisol


Low estrogen


Hyperthyroidemia


Hyperinsulinemia

Hyperinsulinemia

Which of the following is used to assess risk of cancer from poor regulation of estrogen metabolism?




Estradiol/Estriol ratio


Pregnenalone/Testosterone ratio


2/16 Hydroxyestrogen ratio


Estrone/Estriol ratio

2/16 Hydroxyestrogen ratio

Cytokine signaling pathways frequently use which type of chemical reaction to transmit and amplify signals?




Dipeptide formation


Glutathione reduction


Sulfation


Phosphorylation

Phosphorylation

The AKT signaling pathway is involved in the initiation of which cellular process?




Mitosis


Apoptosis


Necrosis


Secretion

Apoptosis

Which of the following is true of a laboratory result that lies in the 5th quintile?




*Eighty percent or more of the reference population has values less that this result *There are four quintiles above the value for this result.


*This result may be presumed to be within normal limits.


*According to standard clinical laboratory definitions, this result would necessarily be considered abnormal.

Eighty percent or more of the reference population has values less than this result

For optimal wellness assurance, which of the following is the preferred stage of nutrient deficiency detection?




Biochemical alterations


Diagnosed pathology


Morphological changes


Impaired tissue function

Biochemical alterations

Which abnormality is an indication of potential BH4 deficiency?




Elevated plasma Phe/Tyr ratio


Elevated serum PIVKA II levels


Elevated urinary succinate


Elevated urinary xanthurenate

Elevated plasma Phe/Tyr ratio

A patient with a low urinary N-methylnicotinamide is a candidate for which nutrient addition?




Vitamin B3


Vitamin B2


Vitamin B1


Vitamin C

Vitamin B3

A patient with an elevated level of beta-hydroxyisovalerate in urine is a candidate for which nutrient addition?




Biotin


Vitamin B6


Folic acid


Lipoic acid

Biotin

Serum concentrations of which of the following generally is considered to be the best compound for assessing vitamin D status?




25-Hydroxyvitamin D


1, 25-Dihydroxyvitamin D Ergosterol


Ergocalciferol

25-Hydroxyvitamin D

For a patient with elevated homocysteine, intervention may be focused on which specific nutrient when elevated formiminoglutamate also is found?




5-Methyltetrahydrofolate


Vitamin B2


Vitamin B6


Pantothenic acid

5-Methyltetrahydrofolate

Which of the following is a function NOT served by the single carbon pool?




*Delivery of reducing equivalents to form BH4


*Delivery of formyl groups to form purines


*Delivery of methylene groups to form pyrimidines


*Delivery of methyl groups to form SAMe

Delivery of reducing equivalents to form BH4

Which factor most commonly leads to multiple elevations of essential amino acids in fasting plasma?




Vitamin B6 deficiency


Vitamin K deficiency


Chronic hypochlorhydria


High protein diet

Vitamin B6 deficiency

Early dietary deficiency states of what essential element has been proposed to be revealed by elevated levels in hair?




Calcium


Zinc


Chromium


Manganese

Calcium

You would correctly recommend iron supplementation based on finding which abnormality in a patients record?




Low serum ferritin


Low hair iron


High erythrocyte transferrin


Low urinary iron

Low serum ferritin

Finding very high levels of which element in erythrocytes would be of greatest concern regarding the recent appearance of toxic manifestations in a patient with a history of low urinary selenosugars?




Mercury


Cadmium


Aluminum


Lead

Mercury

Metabolic impacts of some toxic elements are sensitively revealed by measuring intermediates in what pathway?




Porphyrin synthesis


Protein synthesis


Bilirubin degradation


Methionine catabolism

Porphyrin synthesis

What test result might be used to justify intravenous chelation therapy?




Elevated whole blood lead


Low erythrocyte magnesium


A high Phe/Tyr ration in plasma amino acids


Multiple elevated keto-acids on a urinary organic acid profile

Elevated whole blood lead

Which of the following describes the ultimate event that results in greater intestinal calcium absorption due to the action of vitamin D?




*Enterocyte ribosomal synthesis of calbindin is increased


*Magnesium is displaced from calcium transport channels


*The amount of absorbable calcium in the gut lumen is increased


*The overall activity of enterocyte mitochondrial ATP production is stimulated

Enterocyte ribosomal synthesis of calbindin is increased

The principal reason that magnesium is said to be involved in more metabolic reactions that any other element is




*The requirement of Mg in reactions utilizing ATP


*The fact that Mg is required for the action of zinc fingers


*The requirement of Mg for membrane transporter action on several other elements


*The use of the Mg-Lipoate complex in all oxidoreductase reactions

The requirement of Mg in reactions utilizing ATP

Which phrase describes the first step in the assimilation of ingested dietary zinc?




*Release of bound zinc from food complexes that are denatured by gastric acid


*Binding of free zinc to metal ion transporters in enterocyte brush borders


*Transfer of ionic zinc to zinc fingers


*Metallothionein loading with zinc

Release of bound zinc from food complexes that are denatured by gastric acid

Which abnormality is generally produced by having a fasting plasma specimen sit for 2 days in an outside pickup box during August?




Elevated Gln/Glu ratio


Elevated Gly/Ser ratio


Very low phenylalanine


Very low proline

Elevated Gln/Glu ratio

A patient who has been on SSRI medications for 2-3 years is most likely to have a deficiency of which amino acid?




Tryptophan


Gamma-aminobutyric acid


Phenylalanine


Glutamic acid

Tryptophan

In the absence of any other laboratory evidence, finding a pattern of strongly elevated serene with low glycine on a plasma amino acid profile would suggest deficiency of which essential nutrient?




5-Methyltetrahydrofolate


Thiamin


Vitamin C


Vitamin D

5-Methyltetrahydrofolate





S-Adenoxylmethionine therapy is most likely to be helpful in cases where elevation of which amino acid is found?




Phosphoethanolamine


Hydroxylysine


3-Methylhistidine


Taurine

Phosphoethanolamine

Elevated levels of which compound in plasma is predictive of clinical effects due to insufficient nitric oxide?




ADMA


SAMe


NADPH


ACTH

ADMA

Elevated levels of which compound is associated with difficulty in conversion of ammonia to urea?




All others shown


Ornithine


Citrulline


Arginine

All others shown

Which of the following is NOT a process that is dependent on the availability of arginine?




Porphyrin synthesis


Nitric oxide production


Urea production


Protein synthesis

Porphyrin synthesis

Choline is a derivative of which amino acid?




Glycine


Glutamine


Glutamate


Glutathione

Glycine

The BCKDC is an enzyme that requires how many vitamin-derived cofactors?




5


4


3


2

5

A patient who shows a pattern of low levels for threonine, glycine and serine is a candidate for what type of specific amino acid supplementation




Glutathione precursor


Positively charged side chain


Acid-yielding


Branched-chain

Glutathione precursor

A patient with elevated levels of urinary alpha-aminoadipic acid due to an inherited metabolic disorder should avoid supplementation with which amino acid?




Lysine


Threonine


Cysteine


Histidine

Lysine

Tyrosine is the precursor amino acid in the biosynthesis of which compound?




Dopamine


Serotonin


GABA


Melatonin

Dopamine

Hepatic activity of which pathway is responsible for the disposition of excess dietary tryptophan?




Kynurenin


BCKDC


ADMA


Gamma-glutamyl

Kynurenin

In order to rapidly offset acute increases in oxidative stress, homocysteine trans-methylation is inhibited while which pathway is stimulated?




Homocysteine trans-sulfuration


The SN1-SN2 transporter system


Methylation of glycine to form sarcosine


Phenylalanine conversion to tyrosine

Homocysteine trans-sulfuration

Following administration of the radioactive isomer of a certain amino acid, large fractions of the radioactivity was found rapidly and simultaneously to appear in the subjects DNA, RNA, porphyrins, collagen and glutathione. Which amino acid was used?




Glycine


Arginine


Valine


Histidine

Glycine

Which specific compound, appearing at elevated levels in plasma or urine, would best identify a patient who habitually consumes chicken or turkey almost every day?




Anserine


Carnosine


Xanthurenic acid


Pipecolic acid

Anserine

Elevated levels of which of the following fatty acids indicates general PUFA deficiency?




Mead


Alpha linolenic acid


Stearic acid


Oleic acid

Mead

Which of the following is the most abundant PUFA in the average American diet?




Linoleic


Oleic


GLA


ALA

Linoleic

A patient with biotin deficiency is likely to show elevated levels of which fatty acid?




Nonadecanoic


Lignoceric


Myristoleic


Lauric

Nonadecanoic

A laboratory report that shows low levels of which fatty acid is of greatest concern regarding neurological development in a 2 year old child?




DHA


LA


GLA


AA

DHA

What is the principal form of circulating fatty acids in the fasting state?




LDL


Chylomicrons


HDL


Free fatty acids

LDL

Counting the terminal methyl group, how many carbon atoms are present following the double bond most distant from the carboxylic acid in an omega-3 fatty acid?




1


2


3


4

2

Which class of fatty acids can enter the beta-oxidation cycle without the involvement of the carnitine shuttle?




Medium chain


Long chain


Very long chain


Odd chain

Medium chain

Why does the level of arachidonic acid tend to fall in patients who take large doses of flax oil daily for many weeks?




*Competitive inhibition of omega-6 fatty acid binding to delta-6 desaturase enzymes


*Retarded desaturase activity due to accumulation of linoleic acid in cell membranes


*Biliary stimulation due to high unsaturated fatty acid intake


*Increased rates of peroxisomal arachidonic acid oxidation due to rising oleic acid levels

Competitive inhibition of omega-6 fatty acid binding to delta-6 desaturase enzymes

Why is DHA extremely slow to rise when infants are fed formulas supplemented with flax oil?




*The peroxisomal degradation step required to yield DHA is very slow and inefficient


*The high tissue content of ALA slows the release of EPA by PLA2 enzymes


*Flax oil stimulates the removal of EPA from cell membranes for eicosanoid synthesis


*Flax oil stimulates the removal of DHA from cell membranes for eicosanoid synthesis

The peroxisomal degradation step required to yield DHA is very slow and inefficient

Increased PUFA intake signals the human fat-sensing system to stimulate which process?




Peroxisome proliferation


Peroxisome degradation


Mitochondrial transport of saturated fatty acids


Electron transport system uncoupling

Peroxisome proliferation

Essential fatty acid deficiency results in rising levels of which fatty acid?




Palmitoleic


Arachidonic


Linoleic


Hexacosanoic

Palmitoleic

Which fatty acid ratio elevation is frequently found in patients who display inordinately strong responses to inflammatory stimuli?




AA/EPA


LA/DGLA


Stearic/Oleic


Triene/Tetraene

AA/EPA

Specific concern about a patient's calcium and vitamin D status would be especially confirmed by which test result?




*Elevated plasma hydroxylysine and hydroxyproline


*Low levels of sarcosine and anserine


*Elevated erythrocyte saturated fatty acids


*Low levels of plasma taurine and cystine

Elevated plasma hydroxylysine and hydroxyproline

A patient who shows steadily falling levels of erythrocyte arachidonic acid after initial normal levels were found would be suspected of excessive intake of which dietary oil?




Fish


Borage


Coconut


Corn

Fish

Other than dietary magnesium intake, erythrocyte magnesium levels are directly related to what metabolic factor?




Glutathione status


Calcium balance


Serum glucose homeostasis


Thyroid hormone output

Glutathione status

What cell type failure most directly and specifically contributes to multiple low essential trace elements being found in blood or urine?




Parietal cells


Pancreatic beta cells


Enterocytes


Periportal hepatocytes

Parietal cells

Among reports in the medical literature, which is the most commonly used specimen for arsenic exposure screening?




Urine


Serum


Whole blood


Hair

Urine

Based on finding that a patient with greatly elevatedhomocysteine has normal levels of urinary FIGLU and methylmalonate, which specificvitamin supplementation is likely to result inlower risk for cardiovascular disease?




Pyridoxine Tetrahydrobiopterin


Vitamin B12


Folic acid


Both c. and d. above are valid responses.

Pyridoxine

Which specific nutrient supplementation is most directly indicated for a patient with greatly elevated urinary quinolinate and very low plasma tryptophan?




Niacin


Manganese


Thiamin


Vitamin D

Niacin

Which laboratory result would provide biochemical confirmation of functional impact from a genetric polymorphism that impairs metabolism of catecholamines?




Low urinary VMA and HVA


High urinary VMA and HVA


High plasma Phe and low Tyr


High urinary picolinic acid

Low urinary VMA and HVA

A laboratory report that shows a pattern of low rangelevels for multiple trace elements suggests what underlying physiological failure?




Insufficient gastric acid output


Insufficient thyroid gland function


Overactive adrenal hormone output


Overactive serotonin output by chromaffin cells

Insufficient gastric acid output

When a patient's laboratory report shows very low zinc, what other abnormality takes on greatly added significance regarding need for clinical management?




Elevated blood cadmium


High erythrocyte magnesium


Elevated urinary mercury


Low stool predominant bacteria

Elevated blood cadmium

If you had been monitoring a patient's urinary mercury levels monthly and notice a sudden increase, what kind of treatment procedure would be suspected as a major contributing factor?




Dental amalgam removal


Oral anti-fungal therapy


Radiation for cancer


Multiple weekly colonic therapy

Dental amalgam removal

For a patient who is in a state of strong negativecalcium balance, which profile is most likely to show greatly elevated calciumconcentration?




Hair


Urine


Erythrocyte


Plasma

Hair

If you were requested to prepare a one day DMSA dosingschedule for a patient, what laboratory profile would you expect to be ordered onthat patient?




Urine toxic elements


Urine organic acids


Plasma amino acids


Whole blood volatile solvents

Urine toxic elements

Which potential intervention for a patient would bereinforced by the following laboratoryabnormalities? - low plasma homocysteine, low erythrocyte magnesium, high urinary 8-hydroxy-2’-deoxyguanosine, and low urinarysulfate.



N-Acetylcysteine


Omega-3 fatty acids


Folic acid


Vitamin C

N-Acetylcysteine

Considering the precursor amino acid for thyroid hormoneproduction, which laboratory abnormality would suggest a potential line ofspecific nutritional therapy fora patient with negative autoimmune thyroid antibodies and chronically low thyroid function that is unresponsive toaggressive supplementation of iodine?




Very high plasma Phe/Tyr ratio


Very high urinary HVA/VMA ratio


Very high erythrocyte Zn/Cu ratio


Very high serum 2/16 estrogen ratio

Very high plasma Phe/Tyr ratio

Which laboratory profile would you recommend to confirm suspicion of biotin deficiency?




Urinary organic acids


Erythrocyte trace elements


Plasma amino acids


Serum antioxidant markers

Urinary organic acids

If you find mildly elevated urinary methylmalonic acid for a 10-year-old girl with idiopathic polyneuropathy, which laboratory profile would you recommend for confirmation of specific vitamin deficiency?




Serum vitamin B12


Serum folic acid


Urinary beta-hydroxyisovalerate


Urinary N-methylnicotinamide

Serum vitamin B12

Among the metabolic roles of zinc, which one involvesstructures called zinc fingers?




Gene expression


Cell membrane receptor binding


Enzyme activation


Insulin storage

Gene expression

Measuring levels of which serum protein can providedirect information about a patient’s copper status?




Ceruloplasmin


Ferritin


Albumin


Prealbumin

Ceruloplasmin

Use of which specimen for measuring potassium concentrationhas the strongest scientific support for assessing potassium deficiency?




Erythrocyte


Serum


Hair


Urine

Erythrocyte

Which urinary organic acid profile elevated result would be suspected to have been produced by finding that the patient had consumed a large serving of bananas and black walnuts with her evening meal before the overnight urine specimen collection for the test?


5-Hydroxyindoleacetate 8-Hydroxy-2’-deoxyguanosine


Xanthurenate


Tricarballylate

5-Hydroxyindoleacetate

Therapy with which type of drug frequently causeselevation of urinary 5-hydroxyindoleacetate?




Serotonin reuptake inhibitors


Gamma-butyric acid reuptake inhibitors Dopamine reuptake inhibitors


N-Methyl-D-aspartate inhibitors

Serotonin reuptake inhibitors

Which laboratory finding tells you that a patient has anincreased risk of kidney stone recurrence?




Low urinary citrate


Low urinary zinc


Low urinary taurine


Low urinary 25-hydroxycholecalciferol

Low urinary citrate

Which of the following compounds is NOT a tricarboxylicacid?




Succinate


cis-Aconitate


Citrate


Isocitrate

Succinate

Dietary deficiency of which vitamin causes thesituation known as the “Folate Trap?”




Vitamin B12


Vitamin B6


Biotin


Folate

Vitamin B12

A defect in which regulatory system is indicated by finding the pattern of very high glutamic acid and very low glutamine in a plasma amino acid profile for a 4 year old boy with severe hyperactivity?




SN1-SN2 transporter


Zinc fingers


Catecholamine synthesis


Dimethylselenide formation

SN1-SN2 transporter

Which antioxidant is found in erythrocytes at levelsnearly 10 times those found in blood plasma?




Taurine


Tocopherol


Glutathione


Magnesium

Taurine

What vitamin-derived enzyme cofactor containspantothenic acid?




Coenzyme A


Pyridoxal-5-phosphate


Phylloquinone


Coenzyme Q10

Coenzyme A

Which component of biological membranes is most highlysusceptible to hydroxyl radical attack?




Polyunsaturated fatty acids


Saturated fatty acids


Cholesterol


Steroid hormones

Polyunsaturated fatty acids

If glycine is to be administered to support Phase IIdetoxification, what vitamin also is specifically indicated?




Pantothenic acid


Vitamin B12


Ascorbic acid


Thiamin

Pantothenic acid

Which compound has the unique function of being simultaneouslyrequired for the activated methyl-supply system and theglutathione-formation system?




Homocysteine


Dimethylglycine


Glutamine


Glutamic acid

Homocysteine

Which laboratory abnormality would be the most ominous as a risk factor for a chronic pain patient who has a tendency to overdose her acetaminophen?




Low plasma methionine


Low serum vitamin D


Elevated urinary hydroxymethyglutarate


Elevated erythrocyte copper

Low plasma methionine

What region of the normal human intestinal tract has thegreatest rate of increase in bacteria populations per inch of transit?




Ileum


Duodenum


Ascending colon


Sigmoid colon

Ileum

Which food-specific serum antibody class is testedprimarily to determine the presence ofintestinal hyperpermeability?




IgG


IgA


IgE


IgM

IgG

Why do microbiological culture techniques performed in routine clinical laboratory services fail to detect the large majority of bacteria that occur in stool specimens?


*The bacteria are strict anaerobes *Specimen transport produces falsely elevated results


*There are no growth media with adequate nutrient compositions


*Organotoxins suppress the growth of most bacterial in cell culture

The bacteria are strict anaerobes

Measuring breath hydrogen after an oral bolus of glucoseis a test used to detect which condition?




Transitional gut bacterial overgrowth


Biotin deficiency


Mitochondrial toxicity


Carbohydrate malabsorption

Transitional gut bacterial overgrowth

What condition is revealed by finding a large number of2+ to 4+ results for food-specific IgG4 concentrations in serum?




Intestinal hyperpermeability


Iodine deficiency


Protein-calorie malnutrition


Food poisoning

Intestinal hyperpermeability

A patient whose diet contains very low levels of polyphenols may have false negative results for which test?




Urinary microbial markers


Stool sIgA levels


Caffeine clearance


Schillling test for vitamin B12 absorption

Urinary microbial markers

What compound is a precursor in human cells fortetrahydrobiopterin production?




GTP


Folinic acid


Tyrosine


Glutamine

GTP

Your patient reveals that s/he has been supplementingwith high doses of fish oil for years and always cooks with safflower oil and cornoil. Based on this information, what analyte(s) would you suspect might be elevated?




Suberate


Adipate


Lipid peroxides


Both a. and b. are valid responses

Lipid peroxides

Concurrent elevations of urinary L-lactate and pyruvatehave been shown to respond favorably to which vitamin supplementation?




Lipoic acid


Ascorbic acid


Pantothenic acid


Folic acid

Lipoic acid

Aggressive biotin supplementation would be indicated for a patient with which abnormality?




High urinary beta-hydroxyisovalerate


High serum undercarboxylated osteocalcin


High EGR activity coefficient


High erythrocyte transketolase index

High urinary beta-hydroxyisovalerate

A patient with a low serum transferrin level is acandidate for supplementation of which nutrient?




Iron


Choline


Calcium


Iodine

Iron

When glutathione becomes oxidized in a reaction that removes an oxygen radical, which compound is the co-substrate for the conversion back to reduced glutathione?




NADPH


Catalase


Alpha tocopherol


Taurine

NADPH

Increased intake of which nutrient is most specificallyindicated for a patient with hyperinsulinemia?




Chromium


Calcium


Copper


Choline

Chromium

Which specific nutrient supplementation is most directlyindicated for a patient with greatly elevated serum levels of citrulline andornithine?


Balanced amino acids


5-Methyltetrahydrofolate


Magnesium L-Arginine


The combination of b. and c. above

Magnesium

Which specific nutrient supplementation is most directlyindicated for a patient with a greatly elevated plasma phenylalanine to tyrosineratio?


Iron


L-Phenylalanine


N-Acetylcysteine


Mixed tocopherols

Iron

Folic acid supplementation is indicated when a LOW result is found for which laboratory test?




Plasma histidine


Plasma methionine


Urinary pyroglutamate


Serum homocysteine

Plasma histidine

When a patient is found to have high levels of LA andGLA, but a low level of DGLA on a plasma fatty acid profile, what specific nutrientintervention is suggested? p 292




Zinc


Iron


Primrose oil


Fish oil

Zinc

Insufficiency of which hormone is associated with impaired conversion of beta carotene to vitamin A?




Thyroid


DHEA


Cortisol


Insulin

Thyroid

A patient who had a lab result showing high urinary tricarballylatewould be a candidate for which nutrient supplementation?




Folic acid


Niacin


Magnesium


N-acetylcysteine


None

Magnesium

A patient with signs consistent with magnesium deficiency that is confirmed by low erythrocyte magnesium is likely to have low status of what other compound with direct effects on magnesium status?




Glutathione


Vitamin E


Eicosapentaenoic acid


Tyrosine

Glutathione

Why would dietary protein intake not be expected to produce elevated levels of amino acids in plasma when the test is done according to usual specimen collection instructions?




*After more than six hours, amino acids from dietary protein do not affect peripheral blood amino acid concentrations.


*The liver prevents any amino acids from dietary protein from entering systemic circulation. *Amino acids are absorbed largely by transfer into the small intestinal lymphatic system.


*The instructions usually say that no protein is to be consumed on the day before the specimen collection is performed.

After more than six hours, amino acids from dietary protein do not affect peripheral blood amino acid concentrations.

Elevation of which compound indicates that inflammatoryresponses are occurring in the brain?




Quinolinic acid


p-Hydroxyphenylacetic acid


Orotic acid


p-Hydroxyphenyllactic acid

Quinolinic acid

A patient with simultaneous strong elevations of urinary citrate, cis-aconitate, isocitrate and orotate is also likely to be exhibiting which other laboratory abnormality?




Ammonemia


Hypercholesterolemia


Lipidemia


Hyperglycemia

Ammonemia