Biochemistry

Histone core + linker DNA

Polymerase I

Primer removal and DNA repair

Polymerase I, II and 3

Proofreading of the newly synthesized DNA strand

Each DNA strand serve as a template for the synthesis of a new DNA strand producing 2 new DNA molecules, each with 1 old and 1 new DNA strand.

DNA synthesis is allways in a 5 ́to 3 ́direction.

Methylates the newly synthesized DNA strand.

MutS, MutL, MutH: winds up the DNA molecule

MutH: cleaves the unmethylated strand at methylated site

DNA helicase: unwinds the DNA strand

Exonuclease I: removes the newly synthesized fragment from the MutH cleavage site to just beyond the mismatch

DNA polymerase III makes the new strand

DNAglycosylase: recognize common DNA lesions and remove the affected base (AP site is formed)

AP endonuclease: cut the DNA strand containing the AP site. A segment of DNA including the AP site is removed.

DNA polymerase I: replaces the removed DNA

DNA ligase: seals the remaining nick

DNA lesion is detected.

Exinuclease: cleaves the DNA on each side of the damage.

DNA helicase: removes the DNA segment.

DNA polymerase (I in Ecoli, ε in human) : fills the gap

DNA ligase: seals the nick

- Repair of pyrimidinedimers with photolyase

- Direct repair of O^6-Methylguanine by O^6-Methylguanine-DNA methyltransferase

- Direct repair of alkylated bases by AlkB

miRNA (micro): Post-transcriptional regulators, silencing of many genes

siRNA (small interfering): Binds to the mRNA and silence it

saRNA (small activating): induce gene activation (long lasting)

snRNA (small nuclear): Processing of pre-mRNA in the nucleus. Part of the spliceosome.

snoRNA (small nucleolar): Guide chemical modifications of other RNAs (methylation or pseudouridylylation)

piRNA (piwi-interacting): transcriptional gene silencing of retrotransposons in germline cells.

rasiRNA (repeat associated small interfering RNA): Establishes and maintaining heterochromatin structure. Silencing transposons and retrotransposons.

qiRNA: inhibiting protein translation

tmRNA: rescues ribosomes (mRNA without stop codon). Facilitates degradation of non-normal mRNA.

mRNA: Encode the amino acid sequence of one or more polypeptides specified by a gene or a set of genes.

tRNA: Read the information encoded in the mRNA and transfer an amino acid to the growing polypeptide chain in protein synthesis.

rRNA: Are constituents of ribosome.

Ribozymes = ribonucleic acid enzymes. They increase the speed of reaction.

Group I introns

Rnase P

rRNA

Spliceosomes

Hammerhead ribozym

Sigma factor is a bacterial transcription initiation factor that enables specific binding of RNA polymerase to gene promoters. It controls promoter recognition and specificity.

Prokaryotic protein involved in the termination of transcription.

Tetracycline: blocks binding of aminoacyl-tRNA to A-site of ribosome.

Streptomycin: prevents the transition from initiation complex to chain-elongating ribosome and also causes miscoding

Chloramphe-nicol: blocks the peptidyl transferase reaction on ribosomes

Erythromycin: blocks the translocation reaction on ribosomes

Rifampicin: blocks initiation of RNA chains by binding to RNA polymerase(prevents RNA synthesis)

Puromycin: causes the premature release of nascent polypeptide chains by its addition to growing chain end.

Actinomycin D: binds to DNA and blocks the movement ofRNA polymerase(prevents RNA synthesis)

Cycloheximide: blocks the translocation reaction on ribosomes

Anisomycin: blocks the peptidyl transferase reaction on ribosomes

α-Amanitin: blocks mRNA synthesis by binding to RNA polymerase.

Protect mRNA and prevent degradation by endonucleases

Promotion of ribosome binding and translation

Regulates nuclear export

Protection

Transport

Translational enhancement

Virus contain both DNA and RNA, retrovirus contain only RNA.

Viruses have transcription process, whereas retroviruses have reverse transcription process. It needs to convert their RNA into DNA before it can insert it into the host genome.

DNA sequence that can change its position within the genome, sometimes causing mutations and altering the genome size.

Molecular chaperones: proteins assisting folding of nascent polypeptides, by preventing wrong folding.Molecular chaperones catalyze the formation of correctly folded, functionally active, native proteins, but they are not part of the product.

Expression of many chaperones is induced by stress, such as by heat,because during heat-stress the probability of wrong folding is higher, therefore cells need more protection.These chaperons are called heat shock proteins (HSP’s).

Cystic fibrosis mutant

Parkinson’s disease

Alzheimer’s disease

Huntington’s disease

Eukaryotes: Ubiquitination (signal of death for proteins) and proteasome (enzyme where proteins are degraded)

Bacteria: Lon (an ATP dependent protease) and other proteases

1. Transcription

2. Posttranscriptional processing

3. mRNA degradation

4. Translation

5. Posttranslational processing

6. Protein degradation

7. Protein trageting and transoprt

1. Transcriptinal mechanims (promoter and RNA polymerases)

2. RNA porcessing (5´capping, 3´poly-adenylation, splicing and alternative splicing)

3. Translational mechanisms (miRNA inhibit translation and degrade mRNA, silencer RNAs degrading mRNA)

3. Epigenetic mechanisms (DNA methylation, histone modification, chromatin remodeling)

DNA sequence that increase theactivities of many promoters in eucaryotes.Enhancers function by serving as binding sites for specificregulatory proteins. An enhancer is effective only in the specific cell types in whichappropriate regulatory proteins are expressed.

1. Neurotransmitters - nervous system

2. Hormones - Endocrine system

3. Cytokines - immune system

Insulin, glucagon, somatostatin, hypothalamic (releasing) hormones, pituitary hormones

Synthesis: proteolytic cleavage of the precursor proteins

Mode of action: bind to receptors in the plasma membrane

Epinephrine and norepinephrine

Synthesis: brain, adrenal glands

Mode of action: act through plasmamembrane receptors

Effects: increased heart rate and blood pressure (increased delivery of O2 to tissues). Increased glucose and ATP production, fatty acid mobilization. Increased glucagon secretion and decreased insulin secretion.

Derived from polyunsaturated fats and produced only when needed. They are paracrine hormones.

Prostaglandins, thromboxanes and leukotrienes

Mode of action: act through plasma membrane receptors.

Steroid hormones are endocrine hormones.

Derived form cholesterol: Cortisol, progesterone, testosteron.

Mode of action: acts through nuclear receptors (intestinal Ca2+-binding protein) --> uptake of dietary Ca2+

Effects: works in Ca2+ homeostasis,regulating balance between Ca2+ deposition and Ca2+ mobilization from bone.

Regulation of gene expression

Biosynthesis: In liver from vitamine-A

Nuclear receptors

Thyroglobulin-Tyr ---> Thyroglobulin-Tyr-I (iodinated Tyr residues) ---> Thyroxine (T4) and triiodothyronine (T3)

Mode of action: through nuclear receptors

Effects: stimulate energymetabolism in theliver and muscle

PEP carboxykinase (gluconeogenesis)

Glucose-6-phosphatase (release glucose to blood)

Glycolysis: Hexokinase 2, Hexokinase 4, phosphofructokinase-1, pyruvate kinase

Regulation of glycolysis/gluconeogenesis: PFK-2/FBPase-2

Pentose phosphate pathway: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase

Fatty acid synthesis: pyruvate dehydrogenase, acetyl-CoA carboxylase, malice enzyme, ATP-citrate lyase, fatty acid synthase complex

- Glycogen synthase (glycogen synthesis)

- Pyruvate kinase (glycolysis)

- Pyruvate dehydrogenase complex (pyruvate to acetyl-CoA)

- Phosphofructokinase-2/fructose-2,6-bisphospatase (glycolysis/gluconeogenesis)

- Hormone-sensitive lipase (triacylglycerol mobilization and fatty acid oxidation)

- Translation initiation

- Translation elongation

- Increase glucose uptake (by stimulating GLUT4 transporter)

- Stimulate glycolysis (by increase prod. of PFK2)

- Increase glycogen synthesis (by inhibiting GSK-3)

It is stimulated by stress, exercise, fasting ( increased [AMP])

It stimulates glucose uptake and transport, glycolysis, fatty acid uptake, beta-oxidation

HMG-CoA reductase (cholesterol synthesis)

Fatty acid synthesis (ACC - acetyl-CoA carboxylase)

Insulin secretion

Transcription

1. Increased transcription of HIF-1α

2. HIF-1α is phosphorylated

3. HIF-1α increases transcription of other enzymes and proteins (glucose transporter, glycolytic enzymes, lactate dehycrognease, protease)

4. --> ATP production by glycolysis increases and complex IV properties are adapted to low pO2.

SREBP activates HMG-COA reductase as a transcription factor.

SCAP (cleavage-activating protein) prevents release of SREBP

LDL receptor protein ↑

Pyruvate kinase ↑

Hexokinase 4 ↑

Lipoprotein lipase ↑

Acetyl-CoA carboxylase ↑

Glucose 6-phosphatase ↓

PEP carboxykinase ↓F

BPase-1 ↓

Catalyze oxidative decarboxylation:

- Pyruvate dehydrognease

- a-ketoglutarate dehydrogenase complex

- Branched-chain keto-acid dehydrogenase

- Pyruvate decarboxylase (in bacteria)

Also a coenzyme for transketolase in pentose phosphate pathway.

- Methymalonyl CoA mutase

- Methionine synthase

- Acetyl-CoA carboxylase

- Pyruvate carboxylase

- Propionyl-CoA carboxylase

- Methylcrotonyl-CoA carboxylase

Water-soluble vitamin

Coenzyme in oxidation and reduction reactions (FAD)

Prosthetic group of flavoproteins

Coenzyme in oxidation and reduction reactions, functional part of NAD and NADP.

Hydrophobic compounds. Can be absorbed efficiently only whenthere is normal fatabsorption Are transported in theblood in lipoproteins orattached to specificbinding proteins.

D - Calciferol

E - Tocopherols, tocotrienols

K - Phylloquinone: menaquinones

A - Retinol, b-Carotene

Hydrophilic compounds. Function mainly as enzymeco-factors.

B1 - Thiamin

B2 - Riboflavin

B3 - Niacin

B6 - Pyridoxine

B9 - Folic acid

B12 - Cobalamin

B5 - Panthotenic Acid

B7 ;H-Biotin

C - Ascorbic Acid

Hexokinase II is in muscle cells, have high affinity for glucose and is inhibited by its product glucose-6-phosphate.

Hexokinase IV (glucokinase) is in liver cells, have low affinity for glucose and is inhibited by a regulatory protein (not G6P). It is activated by glucose.

Regulated allostericly

Activated by ADP, AMP and fructose-2,6-bisphosphate (F2,6BP).

Inhibited by ATP and citrate.

Activated by fructose 1,6-bisphosphate

Inhibited by ATP, alanine, acetyl CoA, long chain fatty acids.

Glucagon stimulates phosphorylation of pyruvate kinase, which inactivates the enzyme. This happens only in the liver.

Gluocose --> 2 pyruvate

1. 2 lactate

2. 2 acetyl- CoA (enter citric acid cycle)

2. 2 ethanol + 2 CO2

Inhibit: pyruvate kinase, pyruvate dehydrogenase complex

Stimulate: pyruvate carboxylase

Pyruvate dehydrogenase kinase (PDK) phosphorylates PDC --> INACTIVE

Pyruvate dehydrogenase phosphatase (PDP), dephosphorylates PDC ---> ACTIVE

PDK is stimulated by NADH and acetyl-CoA, and inhibited by CoA-SH, NAD+, ADP, pyruvate.

PDP is stimulated by Ca2+, Mg2+, insulin

Insulin: inhibit

Glucagon: stimulate

Epinephrine, norepinephrine: stimulate

Glucocorticoids: stimulate

- Regulation of biosynthesis of FA: ACC

- Regulation of β-oxidation: CAT

- Regulation of cholesterol biosynthesis: HMG-CoA-reductase, transcriptional regulation

- Regulation of ketonebodies: succinyl-CoA

- Regulation of lipid metabolism by signal transduction (AMPK, PPAR)

Insulin, glucagon, glucocorticoids, epinephrine

Cytosol: Fatty acid synthesis

ER: phospholipid synthesis, fatty acid elongation, fatty acid desaturation

Mitochondria: fatty acid oxidation, acetyl-CoA production, ketone body synthesis, fatty acid elongation

Activated by: insulin, citrate

Inhibited by: glucagon, adrenaline, AMP, palmitoyl-CoA

Regulation of ketone body synthesis happens via HMG-CoA synthase.

Stimulated by acetyl CoA.

Inhibited covalently by succinyl-CoA

Degradation of triglycerols to diacylglyderides and monacylgylcerols.

Lipid-binding protein in blood, transport phospholipids, cholesterol and cholesterol esters between organs.

Converts triacylglycerols to factty acids and glycerol.

Mobilization of stored triacylglycerols un adipocytes.

Stimulated by glucagon/adrenaline

-- > PKA activates hormone-sensitive lipase through phosporylation --> triacylglycerols are hydrolyzed --> free fatty acids are released into the blood.

Binds fatty acids and transports them through the blood.

Defect in either glactokinase, glactose-1-phosphate uridylyltransferase or UDP-glucose-4-epimerase.

Complex I: amytal, rotenone, piercidin A

Complex III: antimycin A, myoxothiazol

Complex IV: CN- (cyanide) and CO

ATP synthase: oligomycin, venturicidin

DNP (2,4-dinitrophenol

FCCP

Causing the oxidation to continue even if ATP synthesis is blocked.

- CoQ of the respiratory chain

- Production of ROS in the peroxisome

- Cytochrome P450 monoxygenases

Enzymes and other molecules that help protect the cell from harmfull effects of ROS.

Superoxide dismutase

Catalase

Glutathione: oxidized to donate reducing equivalents to regenerate oxidized cellular molecules

Takes place in the liver.

Function is to maintain the blood glucose levels during fasting.

Activators: Acetyl Coa, glucagon, epinephrine, norepinephrine, glucocorticoids

Activators of glycolysis (inhibitor of gluconeogensis): ADP, AMP, citrate, fructose-2,6-bisphosphate, insulin.

Function: production of NADPH, RNA, DNA, ATP, FADH2.

Location: rapidly dividing cells, such as those of the bone marrow, skin and intestinal mucosa.

Synthesis:

- fatty acid biosynthesis

- cholesterol biosynthesis

- neurotransmitter biosynthesis

- nucleotide biosynthesis

Detoxification:

- reduction of oxidized glutathione

- cytochrome P450 monooxygenases

Glucose-6-deficency lead to NADPH deficiency.

NADPH maintains the supply of reduced glutathione in the cells that is used to remove free radicals that cause oxidative damage.

Gluthahtione peroxidase: 2GSH + H2O2 ---> GSSG + 2H2O.

The G6PD / NADPH pathway is the only source of reduced glutathione in red blood cells (erythrocytes). If there is not enough reduced glutathione in the cells the free radicals produce Heinz bodies in the RBC, which is denatured hemoglobin caused by oxidative stress.

Mutation in transketolase gene, affinity to TPP is decreased --> thiamine deficiency --> severe memory loss, mental confusion, partial paralysis

Glycogen is stored in liver and skeletal muscle.

Liver glycogen is used to maintain blood glucose levels.

Muscle glycogen is used to generate ATP for muscle contraction when is needed.

- Hexokinas/glucokinase

- Phosphoglucomutase

- UDP-glucose pyrophosphorylase

- Glycogen synthase

- Glycogen branching enzyme

Primer for glycogen synthesis.

- Glycogen phosporylase

- Debranching enzyme

- Phosphoglucomutase

- Glucose-6-phosphatase

8 (Synthesis of palmitate need 8 acetyl-CoA = 8 citrate)

Acetyl CoA from pyruvate cannot be transported through the mitochondrial membrane to the cytosol, so it forms citrate together with oxaloactetate, which is transported out through a citrate transporter.

In the cytosol, citrate is reconverted to acetyl-CoA and oxaloacetate, and acetyl CoA process to fatty acid synthesis in the cytosol. Oxaloacetate is reduced to malte and is transported back into the mitochondria.

Animals can only put double bonds before the 10th carbon.

Therefore it is essential for animals to have fatty acids with double bonds >10 in their diet, like lineolate (--> arachidonate)

Steroids inhibit the synthesis of arachidonate from phospholipids ---> no prostaglandins, thromboxjnes or leukotrienes.

Non-steroids (aspirin, ibuprofen) inhibit COX (cyclooxygenase) ---> prostaglandins or thromboxjnes.

HMG-CoA (beta-hydroxy-beta-methylglutaryl CoA)

HMG-CoA lyase --> acetoacetate (ketone body)

--> acetone (acetoacetate decarboxylase) and D-beta-hydroxybutyrate (Hydroxybutyrate dehydrogenase)

HMG-CoA reductase --> mevalonate (cholesterol synthesis)

Chylomicrons

VLDL

LDL

HDL

Activators: insulin

Inhibitors: glucagon, cholesterol, metabolites

Deficiency in the enzyme propionyl-CoA carboxylase, inhibiting the conversion of propionyl-CoA to D-methylmalonyl CoA.

Deficiency of the enzyme methylmalonyl-CoA wpimerase, inhibiting D-methylmalonyl CoA to L-methylmalonyl CoA.

Amino group: urea cycle

Carbon skeleton: citric acid cycle

Glutamate and glutamine

The amino group is transferred through transamination.

the release of NH4+ from glutamate, forming alfa-ketoglutarate. The enzyme for this reaction is glutamate dehydrogenase, which is the only enzyme that use either NAD+/NADP+.

- Amino acids from ingested proteins

- Alanine from muscle (glucose alanine cycle)

- Glutamine from muscle and other tissues (brain)

- Amino acid degradation (liver and muscle)

- Ammonia secretion in kidney tubule form glutamine

- Nucleotide degradation (pyrimidine)

- Intestinal bacteria produce it from amino acids and urea

Ammonia is very toxic. It is quickly protonated to NH4+ in mitochondrial matrix and converted to urea, which is excreted in the kidney.

If the blood ammonium level increase it can cause cerebral edema and increased cranial pressure.

Mitochondria: Carbamoyl phosphate synthetase I and ornithine transcarbamoylase

Cytosol: argininosuccinate synthetase, agininosuccinase and arginase

Aspartate, fumarate and malate

Long term: Regulation of the rates of the synthesis (transcriptional regulation) of the 4 urea cycle enzymes and carbamoyl phosphate synthetase I.

Short term: Allosterically activation. Arginine stimulates the synthesis of N-acetylglutamate by N-acetylglutamate synthase. N-acetylglutamate stimulates the formation of carbamoyl phosphate by carbamoyl phosphate synthetase I.

Ketogenic: produce ketone bodies in the liver

Glucogenic: produce glucose and glycogen

Alanine

Cysteine

Glycine

Serine

Threonine

Tryptophan

Arginine

Glutamate

Glutamine

Histidine

Proline

Isoleucine

Methionine

Threonine

Valine

Phenylalanine

Tyrosine

Aspargine

Aspartate

Allosteric regulation: Each inhibitor produce partial inhibition, all inhibitors together shut down the enzyme.

1. Glycine

2. Alanine

3. Glucosamine-6-phosphate

4. Histidine

5. CTP

6. Carbamoyl phosphate

7. Tryptophan

8. AMP

Covalent regulation: adenylation --> inactive

- Adenylation = (AMP) molecule is covalently attached to a protein side chain

- Adenylation stimulated by: glutamine, Pi

- Deadenylation stimulated by: ATP, alfa-ketoglutarate

Gluthathione

Antioxidation effect: cysteine

It protects proteins for oxidation in erythrocytes. Removes toxic peroxided formed during growth and aerobic metabolism: glutathione peroxidase reaction.

Produced form glutamate, glycine and cysteine.

Tyrosine: dopa, dopamine, norepinephrine, epinephrine

Glutamate: GABA (inhibitory neurotransmitter)

Histidine: histamine

Tryptophan: serotonin

Methionine: spermine, spermidine

Arginine: NO

Because 1 NADH is formed in the malate dehydrogenase reaction (aspartate-argininisuccinate shunt).

Both need energy. They uses ATP which are converted to AMP + PPi.

1. Free fatty acids

2. Beta-oxidation --> Acetyl CoA

Acetyl-CoA:

3. Cholesterol synthesis

4. Ketone body synthesis

5. Citric acid cycle

6. Storage as lipids

7. lipoproteins

6 CO2 molecules

- Pyryvate dehydrogenase complex reaction

- Isocitrate dehydrogenase reaction

- Alfa-ketoglutarate dehydrogenase complex reaction

Creatine: phosphocreatine is an energy reservoir in skeletal muscle during light activity or rest. Can rapidly regenerate ATP from ADP

Creatine kinase: creatine <--> phospocreatine

Carnitine: transport long-chain fatty acids into the mitochondrion and regulate the intramitochondrial ratio of Acyl-CoA to free CoA.

Carnitine acyltransferase: carnitine + acyl-CoA <--> Acyl-carnitine

An enzyme that produces primary transcript RNA. RNA polymerase is necessary for constructing RNA chains using DNA genes as templates, a process called transcription.

RNA-dependent RNA polymerase or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template.

2H2O + 2NADP+ ---> O2 2NADPH + 2H+

Aspartate, Mg2+

Splicing: snRNA (small nuclear) - part of the spliceosome.

Maturation of rRNA: snoRNA (small nucleolar)

= proofreading activity

Amino acid tRNA synthetase and tRNA interaction will recognize the tRNA that belongs to which amino acid. Get right anticodon forthe right amino acid.

RBCand neurons only

1. Glycolysis: glucophospho isomerase (energy production)

2. Gluconeogenesis: glucose 6-phosphatase (remove P toincrease blood sugar concentration)

3. Pentosephosphate pathway: Glucose 6-phosphatedehydrogenase (Ribose and NADPH production)

4. Glycogen synthesis: phosphoglucomutase (glycogen storage)

HIF1 α (Hypoxia-inducible factor 1, α unit) --> Erythropoietin --> RBC production (since oxygen levelaccommodate to it)

1. Number of Carbons/2 = Number of Acetyl CoA formed

2. Number of rounds in the Beta-oxidation necessary for converting the whole fatty acid to Acetyl Co A units = Number of Acetyl CoA - 1 = NADH and FADH2

3. NADH yields 2.5 ATP and each FADH2 yields 1.5 ATP. Multiply the number of rounds with 4.

4. Multiply the number of Acetyl CoA times 10 (10 ATP in each round of citric acid cycle)

5. Minus two ATP that were used for the activation of the fatty Acid.

Ketone bodies are produced from fat, converted to acetyl-CoA and then transported to the brain where it is used for energy. This prevent amino acid degradation, ketone bodies is used instead.

1. High glucagon levels = low glucose levels in the blood

2. Glucose-6-phosphatase enzyme (only in the liver) - covert glc-6-P --> glucose

3. GLUT7 transporter (transport glucose from ER

4. GLUT 2 transporter (release glucose to the bloodstream)

Glutamate dehydrogenase

Glutaminase

Serine dehydratase

Adenosine deaminase

Passive immunity = when maternal antibodies are transferred to the fetus through the placenta.

IgG is the only immunoglobulin that can pass through the placenta. It protect against bacterial and viral infections in fetuses.

Malic enzyme: malate <--> pyruvate

Glucose-6-phosphate dehydrogenase: glc-6-P <--> 6-phosphoglucono lactone

6-phosphogluconate dehydrogenase: 6-phosphogluconate --> ribulose-5-P

Pyruvat-Dehydrogenase-complex

Citrat-Synthase

Nucleotides added before the polymerase dissociates.

Polymerase I: 3-200

Polymerase II: 1500

Polymerase III: > 500 000

Ribosomal binding site inthe mRNA, generally located 8 basepairs upstreams for the AUG start codon.

Retinoic acid

Vitamin D

Thyroid

Steriod

Proofreading action. It is not able to dorepair on the template, and mutations are very common (may cause immunityagainst drugs).

Gluconeogenesis

Urea cycle

1. Liver proteins

2. Nucleotides

3. Hormones

4. Porphorins

5. Urea Cycle

6. Gluconeogenesis

7. Acetyl-CoA:

TCA cycle

Fatty Acids

G protein --> Adenylate Cyclase --> cAMP --> PKA

Phosphorylation, carboxylation, methylation, sulfation, hydroxylation on the side chains.

1. Modifications on both terminal ends

2. Loss of sinal sequences

3. Modifications of individual amino acids

4. Glycosylation: attachment of carbohydrate side chains

5. Acylation:prenylation, farnesylation

acetylation/deacetylation

6. Addition of prosthetic groups

7. Proteolytic processing

8. Disulfide crosslink formation

It has an isoprene structure that is important in the glycosylation of proteins.

HDL > LDL> IDL > VLDL > chylomicron

LDL > HDL > IDL > VLDL >chylomicrons

It detoxifiesthe body of drugs and toxins by hydroxylation.

IgM, A, D, G,E.

IgE

RNA polymerasedoesn’t need a primer

RNA polymerasehas no 3’->5’ exonuclease activity

No proofreading

The template ismethylated.

They are the main components of methyl directed mismatch repair. They winds up the DNA molecule.

Prokaryotes:Sigma Factor

Eukaryotes:TATA binding protein

Complex IV

Cytochrome C

Complex III

Malonyl-CoA

Aldolase reaction

Fructose-1,6-bisphosphate <--> dihydroxyacetonephosphate + glyceraldehydphosphate

Isocitrate lyase

Malate synthase

Glyoxylate cycle

TPP (B1) -> Thiamine

FAD (B2) -> Riboflavin

CoA-SH (B5) -> Pantothenic acid

NAD (B3) -> Niacin

Hexokinase (1), phosphofructokinase 1 (3), pyruvate kinase (10)

Pyruvate carboxylase(1), PEP carboxykinase (2), fructose-1,6-bisphosphatase (9), glucose 6-phosphatas (11)

1. Gluconeogenesis

- Pyruvate carboxylase, PEP carboxykinase, Enolase, Phosphoglycerat mutase, Phosphoglycerate kinase, glyceraldehyd phosphate dehydrogenase, triose phosphate isomerase, aldolase, fructose-1,6-bisphosphatase, phosphohexose isomerase glucose-6-phosphatase

2. Acetyl-Coa

-Aerobic

- Pyruvate dehydrogenase complex

3. Lactate

-Anaerobic

- Lactate dehydrogenase

4. Oxaloacetate

-Pyruvate carboxylase

F-1-p -> dihydroxyacetone-phosphate and glyceraldehyde. Glyceraldehyde needs to become phosphorylated, this means that 1 ATP is invested during glycolysis

31 or 33 depending on which transport is used

Mostly regulated by changes in HMG-CoA reductase

1. Rate of synthesis of HMG-CoA reductase mRNA is regulated by sterol regulatory element binding protein - transcriptional regulation of cholesterole synthesis

2. Rate of translation of HMG-Coa reductase mRNA is inhibited by nonsterol metabolites derived from mevalonate and dietary cholesterol

3. Degradation of HMG-CoA reductase

- Two domains, cytoplasmic and membrane

- If the membrane undergoes structural changes this can make the enzyme more susceptible to proteolysis

4. Phosphorylation decreases the activation of HMG-CoA reductase

Amino acids -> Glycine, proline, methionine, serine, arginine,hydroxproline etc

Glycine, proline and hydroxproline are in abundant

- Glycine is every third residue

Vitamins -> Vitamin C is important for enzymes which synthesize hydroxyproline

CAP

- Attached to 5'end of RNA with triphosphate group

- Protect mRNA

- Ribosome binding

Poly A tail

- Protection, transport, translational enhancement

Splicing

Editing

Ribozymes

miRNA (micro): Post-transcriptional regulators, silencing of many genes

piRNA (piwi-interacting): transcriptional gene silencing of retrotransposons in germline cells.

Amino acid tRNA synthetase and tRNA interaction will recognize the tRNA that belongs to which amino acid. Get right anticodon for the right amino acid.

Glucose is an allosteric inhibitor of glycogen phosphorylase

Insulin will also inhibit by affecting Gm or glycogen targeting protein, and phosphorylating it once, causing it to be associated with the GM complex.

In the complex the glycogen phosphorylase is inactive.

- Glycogen is synthesized

Phosphorylase b kinase will be upregulated by

- glucagon (liver)

- epinephrine, calcium and AMP in muscle

1. Activated ribose + base -> nucleotide

2. Activated ribose+amino acid + ATP + CO2 + etc -> nucleotide

Ketoacyl synthase, aka 3-ketoacyl-ACP synthase

Cholesterol -> progesterone

- Mode of action through nuclear receptors

- Cortisol, aldosterone, testosterone

Thyroid hormones

Retinoid hormones

Ribonuclease

- A family of non-sequence-specific endonucleases which catalyze the cleaving of RNA

- Activated only when cAMP is present

- Glucagon and epinephrine trigger actiivation cascade

PKC

- Activated by increased DAG concentration or Ca2+ ions

- Signal transduction cascades

2. HMG-CoA reductase

3. 1st Prenyl transferase

4. 2nd Prenyl transferase

?

TPP - thiamine pyrophosphate

Pyridoxal phosphate

Flavin adenin dinucleotide

Nicotinamide adenine dinucleotide

Glutaminase

Serine dehydratase

Arsenite inhibts pyruvate dehydrogenase complex

- No TCA and respiratory chain -> no ATP -> fatal

Arsenate is structurally analog to phosphate, and will inhibits reactions with organic phosphate incorporation -> respiratory chain still runs, but less ATP is produced

phosphorylated on different sites

Insulin phosphorylates GM directly

while epinephrine uses a second site on GM via cAMP -> PKA

- Inhibits glycogen synthesis and enhances glycogenlysis in muscle

p300

Epinephrine/glucagon -> caMP -> PKA -> activates enzymes of gluconeogenesis

1. Insulin -> PKB -> GSK3 -> glycogen synthase covalent

2. Insulin -> PP1

3. Glucagon will causes PKA to phosphorylate glycogen synthase

- Cleave phosphate when bound

- Will causes glycogen degradation

2ADP -> ATP + AMP

Tay-sachs diseases

Niemann-Pick

Gaucher

Krabbes diseases

Accumulation of beta-amyeloid plaques

Tau protein fibrils

PKA -> cAMP

PKC -> Ca2+ and DAG

AMPK -> High cc of AMP, leptin

Absorbed as Fe2+ by DMT1

Transported as transferrin

Stored in apoferritin, in ferric state

RNA virus -> no transverse RNAse, fitted random

Retrovirus -> transverse RNAse, own viral RNA is transcribed into cDNA and inserted into genome of cell

SSB, DNA gyrase, helicase

Cholera, dypheteria, pertussis toxin

Ligase

Helicase

Sigmoid factor

MutH: Cleaves unmethylated strand

MutL and S: seen in DNA methyldgroups, controlling which strands are cleaved

Insulin, glucose uptake and in muscle and fat tissue

Respiratory chain si decoupled form ATP synthase

- Oxidation of the resp. chain and phosphorylation is decoupled

Decoupler proteins -> thermogenin UCP-1, 2,5-DNP, UCP-2, UCP-3

Secondary genetic code

Wobble formation

Proofreading

Ribosomal with aminoacyl t-RNa synthase

Glycolysis in muscle

Gluconeogenesis in liver

Glucose transport from liver to muscle

PPP: CO2 is released

Glycolysis: NAD+ is involved

Both have same intermediates

- Phosphate esters and fructose-6-phosphate

Viral infection of the virus mRNA is degraded and thus removed from cell

By RNA-dependent protein kinases of EIF2 which phosphorylates and inactivates transcription

Enteropeptidase

TNF-alpha can activate ASK/JNK pathway through ROS -> phosphorylation of IRS-1

Glutamine synthase

Von Gierke: glucose-6-phosphatase

Morbus Pompe: Alpha-1,4-glucidase

Cori syndrome: debranching enzyme

McArdle: Glycogen phosphorylase

Desensitization by internalization of the receptor molecules: Arrestin, adrenorecepotrs, g-protein, Beta-ark

siRNA, snRNA, piRNA, snoRNA, rasiRNA, qiRNA

Puromycin

- Embed into A site of both bacteria and eukaryotic ribosomes, and block translation

Actinomycin D

- Bind DNA, prevent RNA

Cycloheximide

- Selectively inhibits eukaryotic ribosomes in cytosol

Strepto mycin and tetracycline

- Example of inhibits which block highly specific bacterial ribosomes, without affecting the eukaryotic ribosomes

No proofreading

RNA pol doesn't need primer

RNA pol has no 3-5 exonuclease activity

RNA+ nATP -> RNA + (AMP)n + PPi

Under polyadenylation is mean to attach a chain to end of 3 end of mRNA

Polydenylation sequence is AAUAAA followed by a GU or U rich sequence

Genes for tRNA and rRNA

Rab-GTP

Acid hydrolyse

V-class proton pumps

Vitamin C:

Proline hydroxylase

Not required squalene monoxygenase

- Cofactor required: NADPH+H+

Alanine cycle transports toxic ammonia from muscle to liver

Muscle

- Alanine aminotransferase will transfer amino group to pyruvate -> alanine

Alanine is transported via blood to liver

At liver alanine is converted to pyruvate and ammonia

- Aminotransferase

Gluconeogenesis uses pyruvate, creating glucose for muscle

Vision, smell and taste

- Sweet, bitter, umami

Salty taste

Proprioception

Pain

Acoustic, hearing

Selfsplicing, lariat structure

Mitochondrial, chloroplast mRNA

Replisome complex: primase, DNA pol, helicase and SSB

In mitochondria: Carbomoyl-phosphate -synthase-1

In cytosol: Arginosuccinate synthase

Cytosol: HMG-CoA reductase -> Cholesterol synthesis

Mitochondria: HMG-CoA lyase -> ketone bodies

HMG-CoA reductase

Squalene synthase

Cyclization of squalene to lanosterol

Allosteric inhibitor: Malonyl- CoA

Reaction based: Acetyl-CoA carboxylase

Glucose-6-phosphate dehydrogenase

6-phosphogluconate dehydrogenase

Malic enzyme

Aldolase reaction

Glyceraldehyde-3-phosphate

Acetyl-Coa for fatty acid synthesis

Pyruvate dehydrogenase complex

Citrate synthase

- citrate into cytosol by ATP-citrate lyase - > Acetyl-CoA

No repair mechanism

In the last step of resp. chain ROS can make a vicious cycle producing more ROS -> broken mitochondria

Glutathione

Glutathione peroxidase

Phosphofructokinase-2

Pyruvate dehydrogenase complex

Glycogen phosphorylase kinase

ATP: Signal transduction, second messenger (cAMP)

GTP: Protein synthesis

CTP: complex lipid synthesis

UTP: Conversion of galactose to glucose-phosphate

HIF-1 alpha has a transcription factor

Proliferation

When bound to Fe2+/3+ it is broken as hydroxylated and the ubiquinated and then degraded

Substituted cobalt Fe+ -> HiF-1 aplha is not -OH and not ubiqu

Insuline sensitive protein kinases

It will inhibit glycogen phosphorylase, which degrades and causes no glycogenlysis -> blood sugar drops

JAK= janus kinase

STAT= signal transducer and activator of transcription

JAK will phosphorylate STAT -> STAT dimerization and moves into nucleus where it participates in gene regulation and expression

Signal transduction via JAK-STAT protein is used by cytokines, interleukins, interferons and erythropoietin

Protonand electron transfere

Glyceraldehyde-3-p dehydrogenase

NADH transfers its electrons complex II

Vitamin B3 - niacin - because of NADP+

Vitamin B1 - thiamine -> TPP in the transketolase reactions

Vitamin A -> retinoic acid

Vitamin D -> calciferol

Forms a complex with tRNA and GTP in translation

Galactokinase

Galactose-1-phosphate uridyl transferase

UDP- galactose- 4 epimerase

Galactokinase reaction

Proprionyl-Coa carboxylase reaction

Fumarylacetoacetate

tyrosine aminotransferase

p-hydroxyphenyl pyruvate dehydrogenase

cAMP -> PKA

cGMP -> PKG

PDK-1 -> PKB

Ca2+, DAG and PDK -> PKC

AMP, leptin -> AMPK

dsRNA -> RKR

Excessive nutration load -> ROS -> H2O2 -> phosphorylation of IRS-1

mTOR, PKC, JNK, TNF, IKK can phopshorylate IRS-1 -> supressed insulin reistance eventually

Follicle acid antagnoist will inhibitconversion of folic acid to tetrahydrofolic acid

Indirectly inhibit purine synthesis, which stops rapidgrowth of cancer cells

Endothelin type 1

O6-methylguanin-DNA methyltransferase

AlkB

Specific ions can enter due to specific arrangement of carboxyl groups in the ion channel

Glutaminase

serine dehydratase

Complex IV of resp chain

superoxide dismutase

Bilirubin oxidase

Parkin: Lack of ubiquination -> accumulation

Alpha-syncein stabilization

Protofibrils

Formation of correctly folded, functionally active, natic proteins -> not a part of the product

Antegrade -> kinesin

Retrograde -> dynein

cAMP -> PKA pathway

will inhibit glycogen synthase via phosphorylation (covalent)

Activate glycogen phosphorylase via phosphorylation (covalent) -> By GM protein and inhibition of PP1

IRE-1

PERK

ATF-6

training causes temporary increase in ROS -> NRF2 activation -> induction of genes for ROS homeostasis

Folding and quality control

superoxide dismutase

Alcohol dehydrogenase

carbonic anhydrase

Right shift

Glutamine synthase - perivenous

Carbamoyl phosphate synthethase - periportal

Antibiotics

Inhibits peptidyl transferase activity of 50s ribosomes in subunit of prokarytoes

It has proofreading activity

Interaction between an aminoacyl-tRNA synthethase and tRNA guarantee the accuracy of the protein biosynthesis

Folic acid in active state -> THF -> purine synthesis

ROS- PARP activation -> apoptosis

SSB, helicase, primase, polymerase, ligase, topoismoserase, gyrase

1. Krebs diseases

2. Alpha thalassemia

3. Chronic leukemia

Causes pyrimidine dimmers

Eukaryotes -> nucleotide excision repair

Prokaryotes -> photolyase

Fructose-1-phosphate dehydrogenase

Aldolase

Measurement of similarity of proteins and nucleotides

complex III, Complex IV and cytochrome C

Inside -> hydroxylation and glycosylation

Outside-> aggregation of proteins

Glucose -> beta cells in pancreas -> glycolysis -> ATP -> Potassium channel -> depolarization > Ca2+ -> insulin release

PLA-2 inhibitor

IkB activator

PPAR

B1 -> thiamine - TPP

B2 -> Riboflavin -> FAD

B3 -> niacin -> NAD

B6 -> pyridoxine -> CoA?

RNA

Glucuronic acid -> water soluble

Inhibits traicylglycerid lipase

activates acyl-CoA carboxylase

Activator -> pyridoxal phosphate

Inhibits -> cyclosporine

CuA

CuB

Heme a

Heme B

Glycogen phosphorylase

Debranching enzyme

Glucose-6- mutase

Glucose-6-phosphatase

Vitamin k dependent carboxylation

Class I introns

23s RNA

Spliceosome

Hammerhead ribozyme

Slidenafil inhibits PDA 5a

cytokines

Chemokines

iNOs

COX II

Omi

cyt c

endo G

AIF

Diablo

Restriction endonuclease

DNA ligase

PXR

Steroids

Coagulation factor

Albumin

Steroid bind to HRE -> PEP carboxylase -> expression of glycerol-3-phosphate decreased

Can bind to FOXO and keep it in the cytosol

Activated phospholipase A2 -> arachidonic acid -> prostaglandins

R+O2+NADPH+H -> H2O + NADP+ ROH

Lysophospholipid and fatty acid from phospholid

Newly created is methylated

PAB

elF4F

PBR

Hb-s has a point mutation in the 6 position

Endocytosis of lipoproteins

activation of LCAT

Receptor ligand in the liver

RNA POL I -> rRNA 18, 5.8, 28s

RNA pol II -> mRNA, snRNA

RNA pol III -> tRNA, 5sRNA

Taq polymerase

DNA pol I

PARP

Remove the 5 leader

3 tail attaches to CCA

Base editing

Glycolysation

Farnesylation

Modification of amino acids

Stimulate synthesis of apoptotic proteins and cell cycle arrest

Trypsin

Pepsin

Chymotrypsin

Alpha amylase

2 alpha, beta, beta', omega and sigma

GLUT 4

EPO

EGF

VEGF

7TM receptors and g protein

Increased production of lipase

Fibroblast into adipocytes

A chaperone in protein folding

Serine

Palmitoyl-Coa

Action, myosin, tropomyosin C, actinin, dynein, kinesin

Glycogenesis

Activation of CREB to CRE -> gene expression

Phosphohexose isomerase

Glucose-6-phosphatase

Glucose-6-phosphate dehydrogenase

Phosphoglucomutase

Telomerase

Pyruvate carboxylase

Acetyl-CoA carboxylase

Propionyl-CoA carboyxlase

proteins of complexes 1,3, 4 and 5

PARP- gamma

Intracellular receptors

Many ligands such as glucocorticoids stimulate lipolysis -

mtDNA polymerase gamma

Replication not limited to s-phase

Both strands are transcribed at once

Cofactor in hydroxylation of HIF-1 alpha