Synthesis of Acetyl CoA Flashcards
What is the substrate for the TCA cycle?
Acetyl-CoA
What enzyme links glycolysis with the TCA cycle by converting pyruvate to acetyl-CoA?
Pyruvate dehydrogenase
True or false: Acetyl CoA can be converted back to pyruvate.
False
What is most pyruvate converted to in resting muscle?
Acetyl-CoA
What is most pyruvate converted to in very active muscle?
lactate
True or false: Fatty acid degradation is an important source of acetyl Co-A.
True
In which part of the cell does the TCA cycle take place?
Mitochondria
What fate does the conversion of pyruvate to acetyl Co-A commit the carbon atoms of carbohydrates to?
Oxidation by the TCA cycle or to the synthesis of lipids.
What moves pyruvate and H+ into the mitochondria after glycolysis?
Pyruvate-H+ symport
True or false: The H+ from glycolysis is brought along with the pyruvate from glycolysis into the TCA cycle.
True
True or false: The pyruvate dehydrogenase complex is large, made of five distinct enzymes, each with their own active site.
False; it is large and made of multiple copies of 3 distinct enzymes, each with their own active site.
What three catalytic coenzymes are necessary for the pyruvate dehydrogenase reaction?
1) Thiamine pyrophosphate (TPP)
2) Lipoic acid
3) FAD
What stoichiometric coenzymes are necessary for pyruvate dehydrogenase reaction?
1) CoA
2) NAD+
Which coenzymes of pyruvate dehydrogenase function as substrates?
CoA and NAD+, the stoichiometric coenzymes
Which coenzymes of pyruvate dehydrogenase function as catalysts and are not permanently altered by their participation in the reaction?
Thiamine pyrophosphate (TPP), Lipoic acid, and FAD
What is the overall reaction catalyzed by pyruvate dehydrogenase complex?
pyruvate + CoA + NAD+»_space;> acetyl-CoA + CO2 + NADH
What regulates the activities of the pyruvate dehydrogenase complex?
Several kinases and phosphatases (it is under covalent modification control).
What is the largest known multienzyme complex?
pyruvate dehydrogenase complex in the mitochondria
Which enzyme in the pyruvate dehydrogenase complex requires TPP (thiamine pyrophosphate) to decarboxylate pyruvate?
Pyruvate dehydrogenase E1
What are the three mechanistic steps of the conversion of pyruvate into acetyl CoA?
1) Decarboxylation
2) Oxidation
3) Transfer of the resulting acetyl group to CoA.
Which is the function of the pyruvate decarboxylate E1 enzyme? What cofactor does it require?
Decarboxylation; TPP
What are the three types of enzymes in the pyruvate dehydrogenase complex?
1) Pyruvate dehydrogenase E1
2) Dihydrolipoyl transacetylase E2
3) Dihydrolipoyl dehydrogenase E3
What is the core of the pyruvate dehydrogenase complex formed from?
60 dihydrolipoyl transacetylase E2 trimers
What is the core of E2 trimers surrounded by in the pyruvate dehydrogenase complex?
30 pyruvate dehydrogenase E1 alpha2beta2 heterotrimers
What is the outer layer of the pyruvate dehydrogenase complex that holds the complex together?
12 E3 dimers and 12 or more E3 binding proteins that bind E3 to the E2 core.
Where is the pyruvate dehydrogenase complex located?
In the mitochondria.
What are the 5 cofactors required by pyruvate dehydrogenase?
1) Thiamine pyrophosphate (TPP
2) Lipoamide (lipoic acid)
3) CoA
4) FAD
5) NAD+
What happens during the first reaction of pyruvate dehydrogenase?
E1 (with TPP) decarboxylates pyruvate (CO2 is lost).
Which cofactor is required by the E2 enzyme in the second reaction of pyruvate dehydrogenase? How does it function?
Lipoamide (lipoic acid); functions as a swinging arm that moves intermediates (the disulfide group) from E1 to E3.
What happens during the second reaction of pyruvate dehydrogenase?
The E2 converts the hydroxyethyl group made in E1 into an acetyl group.
What happens during the third reaction of pyruvate dehydrogenase? What cofactor is required?
E2 catalyzes a transesterification reaction in which CoA is converted to acetyl CoA (with a high energy S-Carbonyl bond). CoA (cofactor) is required.
What happens during the 4th reaction of pyruvate dehydrogenase?
Dihydrolipoyl dehydrogenase E3 regenerates E2’s lipoamide.
What cofactor is required by E3 to regenerate E2’s lipoamide?
FAD
What kind of reaction is the regeneration of E2’s lipoamide by E3?
A disulfide interchange reaction
What happens during the 5th reaction of pyruvate dehydrogenase?
E3 is reoxidized by FAD funneling electrons to NAD+ to yield NADH.
What cofactors are required to reoxidize E3?
FAD and NAD+
Why is arsenic deadly for humans?
It interacts with the thionyl structures (it inhibits lipoamide) in pyruvate dehydrogenase, preventing the formation of acetyl CoA from pyruvate. This stops the TCA cycle from occurring, stopping the production of ATP.
What deadly compound was once used as a treatment for syphilis because it is so much more toxic for bacteria than for humans?
Arsenic
