The Citric Acid Cycle Flashcards
What is the purpose of the CAC?
cellular respiration, and produces NADH and FADH2 for the electron transport chain
How many enzymes work in the CAC?
8
Name the 8 enzymes in order
citrate synthase aconitase isocitrate dehydrogenase alpha-ketoglutarate dehydrogenase succinyl-coA synthetase succinate dehydrogenase fumarate malate dehydrogenase
what is the function of citrate synthase?
the condensation of acetyl-coA and oxaloacetate into citrate
what is the function of aconitase?
isomerization of citrate (OH on C3) into isocitrate (an alcohol). There is an intermediate formed (cis-aconitate). This turns into isocitrate after a hydration (moves the OH to C2)
what is the function isocitrate dehydrogenase?
oxidation of isocitrate into an oxalosuccinate (this is a beta-keto acid intermediate).Oxalosuccinate is decarboxylated into alpha-ketoglutarate. Here is the first generation of NADH and CO2.
what is the function of Alpha-ketoglutarate dehydrogenase?
the oxidative carboxylation of alpha-ketoglutarate into succinyl-coA. Here is the second CO2 and NADH production.
what is the function of succinyl-coA synthetase?
it converts succinyl-coA into succinate. Here GTP is formed. (Using the free energy from the broken thio-ester bond)
what is the function of succinate dehydrogenase?
oxidation of succinates’ central single bond into a trans-double bond of Fumarate. Here FAD is reduced into FADH2
what is the function of fumarase?
the hydration of fumarates’ double bond forming malate
what is the function of malate dehydrogenase?
it reforms oxaloacetate by oxidizing malates’ 2* alcohol to the corresponding ketone. Here NADH is produced, and all acetyl groups have been oxidized to CO2
name the enzymes involved in the steps that produce NADH?
isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase
explain how Citrate synthase works?
an ordered sequential kinetic mechanism, oxaloacetate adds to the enzyme before acetyl-coA. The enzyme is a free dimeric enzyme, it has an open form where the 2 subunits form a deep cleft containing the oxaloacetate binding site, when it binds the smaller subunit turns 18* and the cleft is closed
does citrate have a plane of symmetry?
no, it is prochiral.
how does aconitase work?
it can differ between the pro-S and pro-R carboxymethyl groups of citrate. There is a dehydration, transelimination, rehydration.
how is cis-aconitate formed?
there must be a dehydration reaction in ser 642 alkoxide and takes the pro-R proton of C2 of citrates’ pro-R carboxymethyl group.
there is the loss of OH from C3 by a transelimination of H2O to form cis-aconitate
whats a characteristic of aconitase enzyme?
it has 4Fe-4S redox center clusters.
how does isocitrate dehydrogenase work?
is NAD+ dependant, needs Mn+/Mg+ cofactors. The keto-B acts as an electron sink. First there is the oxidation of NAD+ a its Re-Face.
how does alpha-ketoglutarate work?
it is mediated by a homologous multienzyme complex made of Eo1, Eo2…
what inhibits succinate dehydrogenase?
malonate
is the malate dehydrogenase catalyzed reaction favorable?
no it is very endergonic, however there is a lot of free energy release by the citrate synthase path
for every acetyl-coA entering the cycle how many ATP are made?
10 ATP
name the enzyme that work endergonically (far from equilibrium)
citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase.
what regulates the CAC
allosteric inhibition, competitive feed back inhibition by intermediates, substrate availability, product inhibition
go to notes for amphibolic path way
ehhhhh laziness
