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56 Cards in this Set
- Front
- Back
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What tissues express gluconeogenic enzymes? |
Liver, kidney, some intestinal epithelium |
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What are the 4 enzymes specific to gluconeogenesis (as opposed to glycolysis)? |
1. Pyruvate carboxylase 2. Phosphoenolpyruvate carboxykinase (PEPCK) 3. Fructose 1,6-bisphosphatasae-1 (FBPase-1) 4. Glucose 6-phosphatase |
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Pyruvate carboxylase: cofactor? energy requirement? |
Cofactor: biotin Energy: ATP |
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PEPCK: energy requirement? |
GTP |
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How is the the glucose-6 phosphatase reaction (last rxn in gluconeogenesis) regulated? |
Enzyme is sequestered in the endoplasmic reticulum |
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Which 2 gluconeogenesis enzymes does adipose express? What does it use them for? |
Pyruvate carboxylase & PEPCK Used for glyceroneogenesis |
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What is the total energetic cost of gluconeogenesis? |
4 ADP, 2 GTP, 2 NADH |
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What is the most common precursor for gluconeogenesis? What else can be used for gluconeogenesis? |
Alanine Lactate, oxaloacetate, glycerol |
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With high levels of glucagon, what would be the phosphorylation/activity status of: a) PFK-2 b) FBPase-2 c) G26BP d) PRK-1 e) FBPase-1 |
a) PFK-2: phosphorylated, low activity b) FBPase-2: phosphorylated, high activity c) G26BP: low levels d) PRK-1: inactive e) FBPase-1: active |
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How is pyruvate kinase (PEP -> pyruvate) regulated? |
Glucagon -> phosphorylation of pyruvate kinase, which inactivates it |
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If gluconeogenesis begins with PEP rather than pyruvate, how many high energy bonds are saved? |
4: 2 ATP, 2 GTP |
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What allosterically activates hepatic pyruvate carboxylase? |
Acetyl CoA |
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Transcriptional regulation: what gluconeogenic enzymes are upregulated with high glucagon? What enzymes are down regulated? |
Up: PEPCK, fructose 1,6-bisphosphatase, glucose 6-phosphatase Down: Glucokinase, PFK-1, Pyruvate kinase |
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Transcriptional regulation: what glycolysis enzymes are upregulated with high insulin? What enzymes are down regulated? |
Glucokinase, PFK-1, Pyruvate kinase |
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What is glyceroneogenesis? Purpose? |
Glycerol 3-phosphate is generated from pyruvate Re-esterifying FAs into TGs, which increases insulin sensitivity |
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What enzyme produces glycerol 3-phosphate from DHAP? |
Glycerol 3-phosphate dehydrogenase |
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What does the drug rosiglitazone do? |
Induces PEPCK -> glyceroneogenesis -> FAs made into TGs rather than released |
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What is the product of the PDH complex? |
Acetyl-CoA, CO2, NADH |
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Where does PDH act? |
Mitochondrial matrix |
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How does pyruvate get into the mitochondrial matrix to be acted upon by PDH? |
Pyruvate/H+ symporter |
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What are the 5 cofactors for PDH? |
1. Niacin (B3) 2. Riboflavin (B2) 3. Thiamine (B1) 4. Lipoic acid 5. Pantothenic acid (B5) |
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What is niacin used for? B_? |
Structural component of NAD+ B3 |
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What is riboflavin used for? B_? |
Structural component of FAD B2 |
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What is thiamine used for? B_? |
Active form is thiamine pyrophosphate (TPP), involved in acetyl-transferase function of first 2 reactions B1 |
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What is the lipoid acid used for? |
Aka lipoate (bioactive form), congugated to the complex via an amid bond (lipoamide), involved in 2nd and third reactions (redox & acetyl-transferase) |
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What is pantothenic acid used for? B_? |
Structural component of CoA, used in third reaction B5 |
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What is step 1 of PDH? |
E1 catalyzes the decarboxylation of pyruvate, producing hydroxyethyl-TTP Then E1 oxidizes the hydroxyethyl group to an acetyl |
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What is step 2 of PDH? |
Disulfide of lipoate (on E2) gets reduced, acetyl group is transferred from TPP to thioester linkage on -SH of the reduced lipoate |
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What is step 3 of PDH? |
E2 catalyzes transfer of acetyl group to CoA, forming acetyl-CoA |
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What is step 4/5 of PDH? |
E3 catalyzes regeneration of oxidized lipase, electrons pass first to FAD then to NAD, to produce NADH |
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What part of the PDH complex swings from E1 to E2 to E3, tethering the intermediates? |
Lipoyllysine group |
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What substances activate PDH kinase (which inactivates PDH)? Inhibit PDH kinase (active PDH)? |
Activate: Acetyl-CoA, NADH Inhibit: ADP, pyruvate |
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What substances activate PDH phosphatase (which activates PDH)? |
Ca++ |
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Which substances allosterically regulate PDH itself? Activators Inhibitors |
Activators: CoA, AMP, NAD Inhibitors: Acetyl-CoA, ATP, NADH, LCFA |
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What is the molecular cause of beriberi? Seen in? |
Thiamine deficiency (TTP problems) Seen in malnourished people and alcoholics |
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Disruption of the PDH complex can result in? (3) |
1. Neurological disorders 2. Cardiovascular disorders 3. Lactic acidosis |
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What is the effect of arsenite or mercury poisoning? |
Heavy metals bind tightly to -SH groups, can disrupt E2 lipase cofactor (lipoyllysine) |
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What is the cause of Leigh's disease? Symptoms? |
Defects in genes for PDH complex, primarily in E1 subunit Progressive degeneration of CNS, symmetrical patches of dying brain cells |
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What is the overall equation of the oxidative phase of the PPP? |
Glucose 6-phosphate -> Ribose 5-phosphate, CO2, and NADPH |
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What is the enzyme that catalyzes the first reaction of the PPP: glucose 6-phosphate -> 6-phospho-gluco-d-lactone ? What is important about this step? Produces? |
Glucose 6-phosphate dehydrogenase Commitment step Produces: NADPH |
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What is the enzyme for the second PPP reaction? (Hydrolyzes ring structure) |
Lactonase |
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What is the enzyme for the third PPP reaction? What is produced?
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6-phosphogluconate dehydrogenase Produced: 1 NADPH, CO2, Ribulose-5-phosphate |
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What is the enzyme for the fourth PPP reaction? What is produced? |
Phosphopentose isomerase Produced: Ribose-5-phosphate |
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What are the 3 products produces form non-oxidative PPP, if it proceeds to the end? |
Glucose 6-phosphate Fructose 6-phosphate Glyceraldehyde 3-phosphate |
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What is the order of 4 reactions in the non oxidative phase of PPP? |
1. epimerase 2. transketolase 3. transaldolase 4. transketolase |
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What occurs in the first reaction of NON-oxidative PPP? Enzyme? |
RIbose 5-phosphate -> xylulose 5-phosphate Enzyme: epimerase |
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What is the Carbon breakdown after step 2 of PPP? Step 3? Step 4? |
2: 3/7 3: 6/4 4: 6/6/3 |
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What is required as a cofactor of transketolase? |
Thiamine pyrophosphate (derivative of B1) |
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What is the primary regulator of Glucose 6-phosphate dehydrogenase in the PPP? |
NADPH (allosteric negative regulator) |
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How does Xylulose 5-phosphate affect glycolysis? Pathway? |
Activates glycolysis High levels X5P -> activation of PP2A -> dephosphorylation of PFK-2/FBPase-2 -> increase in F26B levels -> enhanced PFK-1 -> enhanced glycolysis |
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How does Xylulose 5-phosphate effect lipid metabolism? |
It increases NADPH and Acetyl-CoA, therefore stimulating synthesis of FAs |
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What do RBCs use NADPH for? |
To reduce glutathione |
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What is glutathione? (structure) What is its job? |
Tripeptide: glutamate-cysteine-glycine Job: protects tissues and membranes from ROS |
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What glutathione-related enzyme changes GSSG to 2GSH? What does it require? |
Glutathione reductase NADPH |
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What genetic deficiency can be come a problem when people are given sulfa or antimalarial drugs? Symptoms? |
G6PDH (glucose 6-phosphate dehydrogenase) Hemolytic anemia |
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What problem can be seen in alcoholics that leads to hemolytic crisis? |
Thiamine pyrophosphate (TPP) insufficiency Required cofactor for Transketolase |
