KAZAK 3 Flashcards
what reaction does the pyruvate dehydrogenase complex catalyse?
pyruvate + CoA + NAD –> acetyl CoA+CO2+NADH
where does the PDC reaction occur?
in the mitochondrion
how does pyruvate get inside the mitochondria?
through the pyruvate translocase
hydrogen symport (mitochondria pyruvate carrier)
pyruvate is negatively charged, coupled with proton to make a neutral charge when it enters the mitochondria
what is the size of the PDC?
9.5 megadaltons
how many coenzymes are required for PDC to work?
5
which protein of the PDC complex is where the most regulation happens?
E1 - pyruvate dehydrogenase
what are the steps of the PDC reaction?
- pyruvate is decarboxylated, releases CO2 (irreversible step) by E1
- TPP is added to pyruvate to make hydroxyethyl TPP (TPP is regenerated)
- hydroxyethyl TPP becomes acetyl-dihyrolipoamine by adding lipoamide (held by disulfide bonds), done by E2
this reduces the sulfurs - CoA is added to acetyl-dihyrolipoamine, makes acetyl CoA
- reduced lipoamine is oxidised by FAD, which itself becomes reduced
- FAD is oxidised by NAD, which is itself reduced to NADH
lipoamide is regenerated
what are the advantages of multi enzyme complexes?
minimised distances for substrates in between active sites
increased reaction rate
metabolic intermediates immediately go from active site to active site (side reactions are minimised, protection for chemically dangerous intermediates)
coordinated control of the reactions
which is the enzyme in the PDC that generates the acetyl CoA?
E2
what doe Coenzyme A function as
functions as a carrier of acetyl and other acyl groups
what are characteristics of Acetyl CoA?
acetyl thioester
high energy compound (high energy hydrolysis)
has a high acyl group transfer potential and can donate the acetyl group to several acceptors
entry point of CAC
how is PDC regulated by allostery?
NADH and acetyl CoA inhibit the enzyme
product inhibition
prevents useless consumption of pyruvate
what is the difference between allosteric regulations and covalent regulations?
allosteric; metabolites pathways communicate to the cell
covalent: regulated by hormones, external cues
how is the PDC regulated by phosphorylation?
the active form of E1 (pyruvate dehydrogenase) can be converted to the inactive form by phosphorylation with PDH kinase
it can be reactivated by PDH phosphatase (takes the phosphate off)
what activates and inhibits PDH kinase?
activated by ATP, NADH and acetyl CoA
inhibited by pyruvate, ADP