Lecture 6 - TCA Cycle & Bioenergetics Flashcards
pyruvate dehydrogenase complexes (PDC):
catalyses the committed step of the conversion of pyruvate to acetyl-CoA
what is the irreversible committed step controlled by in the TCA?
(a) product (NADH & Acetyl-CoA) inhibition (allosteric control)
(b) a reversible phosphorylation (covalent modification)
what does the PDC compromise of?
the PDC compromises of 5 co-enzymes: FAD, CoA-SH, NAD+, TPP & Lipoate
what subunits are present in the PDC complex?
there are 3 subunits present: E1, E2 & E3
what occurs in the E1 subunit of the PDC enzyme?
E1 has the substrate binding site for pyruvate, pyruvate undergoes decarboxylation to its hydroxyethyl derivative on the enzyme E1 bound TPP coenzyme - this reaction gives CO2
what occurs in the E2 subunit of the PDC enzyme?
oxidation of the hydroxyethyl group from TPP to the acetate group takes place on the E2 enzyme. this acetyl group is first transferred to one of the lipoyl-SH groups
the -SH group, transesterification of CoA to form acetyl CoA and fully reduced form of lipoyl group
how do the E2 & E3 subunits of PDC interact with one another?
Transfer of two hydrogen atoms from the reduced lipoyl groups of E2 to the FAD of E3 by dihydrolipoyl dehydrogenase. This results in regeneration of oxidised form of lipoyl-lysyl group of E2
what is the final enzymatic event that is catalysed by PDC?
the transfer of hydride ion (proton) from FADH2 to NAD+ forming NADH2
allosteric control of PDC:
•The binding of end products, NADH and Acetyl CoA both inhibits PDC activity
•If there are enough end products, PDC will be inactive.
•The binding of substrates, pyruvate and ADP to the PDC promotes the enzyme catalytic activity of PDC
•If there are more substrates available, PDC will be active.
covalent modification of PDC:
•A serine residue on the pyruvate dehydrogenase enzyme complex is phosphorylated by PDC kinase (PDK). This phosphorylation of serine leads to an inactivation of PDC
•PDC has the phosphate group removed by PDC phosphatase. PDC is activated reversibly by this PDC phosphatase.
TCA cycle is the same as:
the Krebs Cycle
TCA Cycle 1 Enzyme Reactions Step by Step:
1.The TCA cycle starts when an acetyl-CoA condenses with an oxaloacetate catalysed by citrate synthase enzyme to give citrate.
2.Citrate is isomerized by aconitase enzyme to give isocitrate.
3.Isocitrate is decarboxylated by isocitrate dehydrogenase enzyme to give α-ketoglutarate. This reaction also gives CO2 and NADH.\
4.α-ketoglutarate is decarboxylated by α-ketoglutarate dehydrogenase complex enzyme to give succinyl Co-A. This reaction also gives CO2 and NADH.
TCA cycle 2 step by step:
1.Coenzyme A of succinyl-CoA is removed by succinyl CoA synthase (succinate thiokinase) enzyme to give succinate. This reaction also generate a GTP.
2.Succinate is oxidized by succinate dehydrogenase enzyme to give fumarate. The hydrogen acceptor in this reaction is FAD+ that is reduced to FADH2.
3.Fumarate is then reduced by hydration catalyzed by fumarase enzyme to form malate. of H + in the inter membrane space of the mitochondria.
4.Finally, malate is oxidized by malate dehydrogenase enzyme to form oxaloacetate. NAD+ is reduced in this reaction to give NADH.
stages of action in the electron transport chain:
1.Complex I (NADH-Q oxidoreductase) first transfers electrons (e-) from NADH to ubiquinone (Q).
2.Complex II (Succinate-Q reductase) transfers electrons (e-) from FADH2 to ubiquinone (Q).
1.Electrons (e-) are then passed down to complex III (Q-cytochrome c oxidoreductase complex).
2.Cytochrome c receives and transfers electrons from complex III to complex IV (cytochrome c oxidase).
3.Complex IV(Cytochrome c oxidase) uses molecular oxygen as an oxidizing agent and reduces it by donating electrons. This results in reduction o
purpose of the electron transport chain:
purpose of the electron transport chain (ETC) is to transport protons (H+) from the matrix to the intermembrane space across the inner membrane of mitochondria via complexes I, III, and IV.
