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22 Cards in this Set
- Front
- Back
What are the different pathways of glucose utilization by cells?
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-Glycolysis (energy production)
-Glycogen synthesis (storage mainly in liver and skeletal muscle) -Conversion to UDP-glucose (glycosaminoglycan, glycoprotein, glycolipid, lactose synthesis) -Pentose-phosphate pathway (NADPH and ribose-5-phosphate production) -Conversion to sorbitol (fructose synthesis, mainly in seminal vesicles) |
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How is glucose taken up by different cells?
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NA+ DEPENDENT GLUCOSE TRANSPORTER (SGLT)
-uptake by intestinal epithelial cells from the digestive tract NA+ INDEPENDENT GLUCOSE TRANSPORTERS (GLUT) -tissue specific -GLUT-2: main bidirectional transporter in LIVER, KIDNEY, PANCREAS -GLUT-4: specific for muscle and adipose tissue -GLUT-4: only INSULIN-REGULATED GLUCOSE TRANSPORTER |
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Explain the glucose conversion to sorbitol and the importance of this process in normal physiology and in diabetes.
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-it can be performed in many tissues
PHYSIOLOGY IMPORTANT (seminal vesicles) -sorbitol converted to fructose -fructose secreted into seminal fluid -sperm cells use fructose as main energy source DIABETES -hyperglycemia: causes excess sorbitol production in lens, retina, nerve, and kidney cells -cells are inefficient to convert sorbitol to fructose -sorbitol accumulates in cells, attracts lots of water causing swelling of the cells -leads to complications in diabetes (cataracts, retinopathy, nephropathy, peripheral neuropathy) |
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What is the difference between aerobic and anaerobic glycolysis?
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difference is how NADH is oxidized back to NAD+
AEROBIC: uses oxygen -oxidative phosphorylation in mitochondria ANAEROBIC: no oxygen -lactate dehydrogenase in cytosol |
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Calculate the ATP and NADH yields of glycolysis from a given amount of glucose.
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Glucose to pyruvate
Aerobic: first phosphorylation step you use 2 ATP to run it -energy generation phase produces 4 ATP (2 for each substrate) NET: 2 ATP 2 NAD+ makes 2 NADH (anaerobic glycolysis there is no net change in NAD+ and NADH |
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What are the metabolites of the glycolytic pathway?
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-glucose 6-P
-fructose 6-P -fructose 1, 6-bis-P -glyceraldehyde 3-P -1,3-bis-Phosphoglycerate -3-Phosphoglycerate -2-Phosphoglycerate -Phosphoenlpyruvate -Pyruvate |
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What are the 3 irreversible steps of glycolysis?
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1. Glucose --> Glucose 6-P (uses ATP
2. Fructose 6-P --> Fructose 1,6-bis-P (uses ATP) 3. Phosphoenolpyruvate --> Pyruvate (produces ATP) |
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Describe the four pathways that metabolize pyruvate.
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LACTATE
-anaerobic glycolysis (lactate dehyrogenase) OXALOACETATE -gluconeogenesis, TCA cycle (pyruvate carboxylase) ACETYL COA -TCA cycle, fatty acid synthesis (pyruvate dehydrogenase) ACETALDEHYDE -only in microorganism (not in the human body) (pyruvate decarboxylase) ---when making alcohol |
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What are the consequences of pyruvate kinase deficiency?
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It causes hemolytic anemia:
-RBC's do not have mitochondria -ATP production is dependent on glycolysis -ATP is necessary for plasma membrane pumps to maintain flexibility of RBC's -with no ATP, RBC's will have abnormal shape and are destroyed by macrophages |
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What are the physiological and pathological conditions that lead to lactic acidosis?
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1. in tissues with little vascularization or in cells that have little/no mitochondria
(cornea & lens of eye, kidney medulla, WBC & RBC's 2. during strenuous exercise in skeletal muscle -increased NADH exceeds oxidative capacity of respiratory chain ---> NADH used by lactate dehydrogenase (causing accumulation of lactic acid in muscle, causing cramps) 3. during collapse of circulatory system (blocking O2 to get into muscles) -myocardial infarction, pulmonary embolism, uncontrolled hemorrhage, shock) -with no O2, cells use anaerobic glycolysis, increasing lactic acid ==> lactic acidosis |
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What are the major regulatory steps and regulated enzymes of glycolysis?
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Glucose --> Glucose 6-P (glucokinase)
-insulin activated, glucagon deactivates Fructose 6-P --> Fructose 1, 6-bis (PFK) -insulin activates, glucagon deactivates PEP --> pyruvate (pyruvate kinase) -insulin activates, glucagon deactivates Insulin/glucagon ratio regulates activity of PFK-1 through allosteric effect of fructose 2, 6-bisphosphate -insulin/glucagon ratio regulates activity of pyruvate kinase through deposphorylation and phosphorylation -insulin and glucagon levels regulate synthesis of key enzymes of glycolysis (transcription) |
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What is the difference between hexokinase and glucokinase? How are they regulated?
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Hexokinase
-most tissues -lower Vmax -lower Km -regulated by glucose-6-P -main utilization in FASTING STATE Glucokinase: -liver, pancreas -higher Vmax -higher Km -regulated by glucose (+) fructose-6-P (-) -main utilization in FED STATE |
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What are the basics of signaling by insulin and glucagon inside the cell?
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Insulin (anabolic) increases insulin after a meal
-produced by pancrease B cells in the FED STATE -stimulates glucose uptake, glycolysis, and glycogen synthesis -downregulates glycogen degradation and gluconeogenesis (inhibits because it has enough glucose in circulation...doesn't need to make any) Glucagon (catabolic) -produced by pancreas a cells in FASTING STATE -stimulates glycogen degradation and gluconeogenesis in liver (needs to produce because none is coming from food) -downregulates glycogen synthesis, glycolysis in the liver (inhibits) |
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How does insulin/glucagon ratio regulate glycolysis in the liver?
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Insulin initiates the dephosphorylation of metabolic enzymes
-if there is a lot of insulin, glycolysis runs because it already has enough glucose in circulation so it makes energy to use else where Glucagon: phosphorylation of metabolic enzymes -inhibits glycolysis in the liver because it needs glucose in circulation |
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What is the mechanism of phosphofructokinase-1 regulation?
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indirectly regulates PFK-1 through synthesis of fructose 2, 6-bisphosphate (allosteric activator of PFK-1)
-with high insulin/glucagon ratio --> increased F-2, 6-P levels --> more active PFK-1 -with low insulin/glucagon ratio --> reduced F-2, 6-P levels --> less active PFK-1 |
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What is the mechanism of pyruvate kinase regulation?
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fructose 1,6-bisphosphate --> + regulation
glucagon (low blood glucose) --> - regulation --glucagon initiates a signaling pathway that phosphorylates (deactivates) pyruvate kinase by protein kinase A -phosphoprotein phosphatase can dephophorylate (reactivate) pyruvate kinase (induced by insulin) |
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What hormones have an effect on the liver?
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glucagon during fasting
insulin during well fed state epinephrine |
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what hormones have an effect on muscle?
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insulin and epinephrine
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What effect on enzymes of glycogen metabolism do each of the three hormones have?
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Glucagon: phosphorylates the enzymes and degrades glycogen metabolism
(during fasting, you want glucose to be made so it activates degradation of glycogen) -insulin: dephosphorylates protein phosphatase and synthesizes glycogen metabolism (insulin means you have enough glucose in the blood, so it will make more glycogen for storage and inhibit glycogen degradation) -epinephrine: phosphorylates the enzymes and degrades glycogen metabolism (same effect as glucagon) |
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How fast is liver glycogen stores depletes?
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within 24 hours of fasting
it is responsible for maintaining blood glucose levels for the entire body |
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What are the 2 energy-producing phases in glycolysis?
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1,3 bis phosphoglycerate to 2,3-bisphosphoglycerate
phosphoenolpyruvate (PEP) to pyruvate (there are 2 of each in glycolysis so combined they would form 4 ATP) |
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What does pyruvate kinase deficiency cause?
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- Red blood cells (RBCs) do not have mitochondria
- ATP production is strictly dependent on glycolysis - ATP is necessary for plasma membrane pumps to maintain the flexibility the RBCs. - In the absence of ATP red blood cells will have an abnormal shape and are destroyed by macrophages. |