TCA cycle Flashcards
Features
cyclic pathway- mitochondrial 8 steps in the cycle Oxidation of Acetyl coA Loss of CO2 Release of electrons Release of energy Intermediates are used elsewhere
Step 1: citrate synthase (irreversible)
Hydrolysis of a high energy intermediate (Citroyl-coA) provides the driving force for the reaction
Large neg delta G
“Open” and “closed” forms of citrate synthase
Homodimer, active site between subunits
Oxaloavetate bunds first, conformational change allowing Acetyl -CoA to bind
Step 2: aconitase (reversible)
Involves a sequential dehydration and hydration reaction to form the isocitrate isomer. The hydroxyl group is now in the desired a- location
Isocitrate formed is rapidly used and pulls reaction to the right. Contains ironsulfur centre to bind substrate to catalysis
Step 3: isocitrate dehydrogenase (irreversible)
Oxidative decarboxylation (loss of CO2) Releases electrons to NAD to form NADH
Step 4: irreversible
Second oxidative decarboxylation step in cycle
Second step releasing electrons to NAD
CoA is the carrier of the succinyl group (not Acetyl group)
Enzyme complex resembles that of PDH
Uses the same E3, same cofactors TOO, lipoic acid, CoA-SH, FAD, NAD
Step 5: reversible
Energy released from breaking thiorster bond drives synthesis of GTP
Recycling of CoA -SH
Step 6:
Releases electrons via FADH2
Succinate dehydrogenase is localised to the inner mitochondrial membrane
The only membrane bound enzyme step in TCA
An electron carrier enzyme
Step 7:
Fumarase to fumarate
Step 8:
Final release of electrons to NAD
Regulation of TCA cycle
Substrate availability- oxaloacetate, limited quantities can impact
Product inhibition- succinyl CoA
Allosteric feedback inhibition - ATP (binds to alternative active site and changed conformation)
Points of regulation
PDH complex- regulates flux of Acetyl coA entering cycle
Citrate synthase
Isocitrate dehydrogenase
Alpha ketoglutarate dehydrogenase
The glyoxylate cycle
In organisms other than vertebrates
Needed in order to convert fatty acids to carbohydrates
Plants have glyoxysome
TCA cycle summary
3 irreversible reactions: Step 3 (CO2 release) and 4 (CO2 release) For each then through the cycle 1 X 2 carbon molecule (Acetyl coA) enters cycle 2 CO2 molecules come out 3 NADH molecules carry electrons 1 FADH2 molecule caries electrons 1 GTP molecule is produced
Krebs cycle summary other
Two carbons added to oxaloacetate by the action of citrate synthase (and Acetyl coA)
Two carbons have been lost as CO2 by oxidative decarboxylation steps
Two oxidised NAD+ cofactors have been reduced to NADH
Succinyl-CoA is converted back into the original substrate for the cycle: oxaloacetate
