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Submitted By: Mohd Ayaz Roll No: 191077
Submitted By: Mohd Ayaz Roll No: 191077
*Step-1: In the first reaction of the citric acid cycle, acetyl-CoA reacts with
oxaloacetate to form citrate. The mechanism for the reaction shows that an
aspartate side chain of the enzyme removes a proton from the a -carbon of acetyl-
CoA, creating anenolate ion. This enolate ion adds to the keto carbonyl carbon of
oxaloacetate and the carbonyl oxygen picks up a proton from a histidine side
chain. This is similar to an aldol addition where the a -carbanion (enolate ion) of
one molecule is the nucleophile and the carbonyl carbon of another is the
electrophile .The intermediate (a thioester) that results is hydrolyzed to citrate in a
nucleophilic addition– elimination reaction
The citric acid cycle
*Step-2: In the second reaction, citrate is converted to isocitrate, its isomer. The
reaction takes place in two steps: The first step is an E2 dehydration in which a
serine side chain removes a proton, and the OH leaving group is protonated by a
histidine side chain to removes a proton, and the OH leaving group is protonated
by a histidine side chain to make it a weaker base (H 2 O) and therefore a better
leaving group. In the second step, conjugate addition of water to the intermediate
forms isocitrate.
The citric acid cycle
*Step-3: The third reaction is the one that releases the first molecule of CO 2 . It
also has two steps. In the first, the secondary alcohol group of isocitrate is
oxidized to a ketone by NAD+. In the second, the ketone loses CO 2 , with Mg 2+
acting as a catalyst.
*Step-4: The fourth reaction is the one that releases the second molecule of CO
2 . The reaction requires a group of enzymes and five coenzymes, known
collectively as pyruvate dehydrogenase complex .The overall result of this
reaction is the transferof an acyl group to CoASH. Thus, the product of the
reaction is succinyl-CoA.
The citric acid cycle
*Step-5:The fifth reaction takes place in two steps. First, hydrogen phosphate reacts
with succinyl-CoA in a nucleophilic addition–elimination reaction to form an
intermediate, which then transfers its phosphate group to GDP.
*The intermediate does not transfer its phosphate group directly to GDP. Instead,
it transfers the phosphate group to a histidine side chain of the enzyme, forming
3-phospho-His, which then transfers the phosphate group to GDP
The citric acid cycle
*Once formed, GTP transfers a phosphate group to ADP to form ATP. The rapid
interconversion of GTP and ATP is catalyzed by an enzyme called nucleotide
diphosphate kinase.
*Mechanism:
The citric acid cycle
* 2 carbons atoms are put into oxaloacetate to create citrate, which are later
released via oxidization the form of two carbon dioxides
Products of citric acid cycle
* 3 molecule of NADH and one molecule of FADH2 are formed from the
oxidation of various intermediary carbon molecules
* These values correspond to the products of one full iteration of the cycle for
one molecule of acetyl-CoA. As each glucose molecule makes 2 molecules of
acetyl-CoA, multiplying these values by 2 gives us the grand total of products
per single molecule of glucose: 4 carbon dioxide, 6 NADH, 2 FADH2, and 2
molecules of either ATP or GTP.