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Unformatted text preview: A is ued by other pathways as well. - the most rate
limniting substrate in the mitondria - OAA binds ﬁ rst and creates binding site of Actyl CoA aand carry out
the reacitn. 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Citrate Is Isomerized by Aconitase to
molecule - make
double bond between
two carbons. add water back and
group to carbon 2
when it was at
c arbon 3. Citrate is a poor substrate for oxidation
So aconitase isomerizes citrate to yield isocitrate
which has a secondary -OH, which can be
Reaction involves a dehydration followed by
hydration to enable an oxidative decarboxylation
to occur in the next step.
Isomerization necessary to carry out oxidation dehydrogenation 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Isocitrate Dehydrogenase Catalyzes the First
Oxidative Decarboxylation in the Cycle
Isocitrate dehydrogenase is a link to the
electron transport pathway because it makes
Rate of formation of -ketoglutarate
determines the rate of the cycle.
Rate liminting the ﬁ rst step where you prduce NADH - NADH will donate electros to trasnport chain - linking the TCA
c ycle to the elctron trasnport chain - going to work together. 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Oxidation & Decarboxylation of Isocitrate First of four redox reactions: oxidation of alcohol group to
Classic NAD+ chemistry (hydride removal) followed by a
Look at the reaction - the hydrozyl group - oxidize through carbil. lose CO2 - oxidiactive
4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Isocitrate Dehydrogenase Allosteric regulation: ADP & NADH Low energy charge. increase rate
of some cycle. decline in
se - feedback
NADH. Now add a 4th enzyme that is
r egulated by energy charge. PFK
pruvate kinase Pryuvate
dehydrozase and cirtrate
dehydrogenze - all regulated by
energy charge. ADP increases
s hift to left. differnet x-axis.
more and more into low energy charge state. This allows the TCA cycle to respond to the energy level of the cell:
High ADP means low ATP & High NADH means the ETC is
functioning at capacity
4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 -Ketoglutarate Dehydrogenase
Thioester bond A second oxidative decarboxylation
This enzyme is nearly identical to pyruvate
dehydrogenase - structurally and mechanistically.
Five coenzymes used - TPP, CoASH, Lipoic acid, NAD+,
Use eneryg in thioester bond to carry out high enery phsophate.
4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 How Is Oxaloacetate Regenerated to
Complete the TCA Cycle? (or ADP)** (or ATP)**
Re **Tissue specificity
Succinyl-CoA Synthetase A substrate-level phosphorylation
A nucleoside triphosphate is made
Its synthesis is driven by hydrolysis of a CoA
thioester bond which is used to form GTP or ATP
4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Succinate Dehydrogenase Is FAD-Dependent Remove hdyrogen. FAD will accept. and
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This note was uploaded on 09/17/2013 for the course MCB 2610 / 200 taught by Professor Feldman during the Fall '12 term at UConn.
- Fall '12