PDH Complex and the CAC (TCA) Flashcards
(37 cards)
What are the some of the sources of Acetyl CoA for the TCA cycle?
- *1) glycolysis- conversion from pyruvate by pyruvate dehydrogenase
2) oxidizing amino acids
3) fatty acid B oxidation
4) two carbons (like ethanol or acetate) and convert them
5) ketone body metabolism
Where does the TCA cycle take place?
the mitochondrial matrix
How does pyruvate enter the mitochondria?
through porin molecules on the outer membrane (note that the inner membrane will not let pyruvate pass through- too tight)
How does pyruvate pass through the inner mitochondrial membrane?
through pyruvate carriers
Where does pyruvate dehydrogenase exist in the cell?
inside the mitochondrial matrix
What are the three enzyme activities of pyruvate dehydrogenase?
1) pyruvate decarboxylase (E1)
2) dihydrolipoyl transacetylase (E2)
3) dihydrolipoyl dehydrogenase (E3)
What is the function of the E1 domain of pyruvate dehydrogenase?
decarboxylates pyruvate
What is the function of the E2 domain of pyruvate dehydrogenase?
transfers acetyl group to CoA
What is the function of the E3 domain of pyruvate dehydrogenase?
reoxidizes dihydrolipoamide
What cofactor does E1 need in order to convert pyruvate to Acyl-TPP
thiamine pyrophosphate (TPP)
What cofactor does E2 need in order to convert Acyl-TPP to Acyl-lipoate?
lipoic acid with sulfur-sulfur bond
The term ‘dehydrogenase’ means taking off how many electrons?
2
What is the first step of the TCA cycle?
this is a condensation run
combine acetyl-CoA to oxalaoacetate (a 4-carbon dicarboxylic acid) to make citrate (a tricarboxylic acid)
What enzyme catalyzes the conversion of acetyl-CoA and oxaloacetate to citrate?
citrate synthase
How does citrate synthase work?
initially it gets oxaloacetate to bind to the protein which causes a change in structure and creates a new binding site for acetyl-CoA. The presence of both then causes another conformational change that stimulates conversion to citrate
What are the two fates of citrate?
1) continue through the TCA cycle
2) be exported to the cytosol to be reconverted to acetyl coA (and oxaloacetate) for fatty acid synthesis. Note that acetyl coA does not have a transporter in the mitochondria so it can only be recycled to the cytosol this way (conversion to acetyl-CoA and oxaloacetate happens by ATP-citrate-liase)
What happens to citrate in the TCA cycle?
it is converted to isocitrate (through an intermediate- cis-Aconitate) by aconitase
How does Aconitase work?
it shifts a central hydroxyl group to permit formation of an alpha-leto acid. This process works by removing water to make cis-aconitate and then re-adding water to make isocitrate (which has the hydroxyl group on a different carbon)
What happens to isocitrate in the TCA cycle?
It is oxidized by isocitrate dehydrogenase to make a-ketogluterate (by giving off Co2 and making NADH)
What are the fates of a-ketogluterate?
1) continue through TCA
2) use as a pre-cursor for amino acid synthesis (for glutamic acid, glutamine, proline etc).- only going to do this in an energy-rich situation
What happens to a-ketogluterate in the TCA cycle?
What are the bi-products?
What enzyme?
it is converted to succinyl-coA by adding CoA-SH and through the enzyme a-ketogluterate dehydrogenase
Bi-products: Co2 and NADH
How many carbons does succinyl-CoA have?
4
What happens to succinyl-CoA in the TCA cycle?
What are the bi-products?
What enzyme?
it is converted to succinate by saucily CoA synthesase
Bi-porducts: CoA-SH, GTP (which is converted to ATP)
this reaction is reversible
What happens to succinate in the TCA cycle?
What are the bi-products?
What enzyme?
it is converted to fumigate by succinate dehydrogenase
Bi-products: FAHD2
