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Submitted by: Mohd Ayaz

Roll No: 191077


METABOLISM
The reactions that living organisms carry out to obtain the energy they need and
to synthesize the compounds they require are collectively known as metabolism .

Metaolism can be divided into two parts: catabolism and anabolism.

Catabolic reactions convert complex nutrient


molecules into simple molecules that can be used
for synthesis. It involves oxidation reaction and
produce energy.

Anabolic reactions synthesize complex biomolecules


from simpler precursor molecules

You are what you eat


catabolism: complex molecules Simple molecules + energy

anabolism: simple molecule + energy Complex molecules


The four stages of catabolism
The citric acid cycle(KREBS CYCLE)
The citric acid cycle
*The citric acid cycle(third stage of catabolism) is a series of eight reaction in
which acetyl group of each molecule of acetyl-CoA- formed by the catabolism of
fats, carbohydrate and amino acids- is converted to two molecules of CO2

*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.

*Step-6: In the sixth reaction, FAD oxidizes succinate to fumarate

*Mechanism:
The citric acid cycle

*Step-7: Conjugate addition of water to the double bond of fumarate forms ( S )-


malate.

*An enzyme-catalyzed reaction forms only one stereoisomer because an


enzyme’s binding site can restrict delivery of the reagents to only one side of
the reactant.
The citric acid cycle

*Step-8: Oxidation of the secondary alcohol group of ( S )-malate by NAD+ forms


oxaloacetate,returning the cycle to its starting point. Oxaloacetate now begins the
cycle again, reacting with another molecule of acetyl-CoA to initiate the
conversion ofacetyl-CoA’s acetyl group to another two molecules of CO 2 .

What are the products of citric acid cycle?


*Taking a step back and looking at all the steps, we can see the ultimate fate of
our carbon molecule and the relevant products of the Krebs cycle. Counting all
the carbon dioxide, NADH, FADH2 and ATP/GTP, we get:

* 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

* 1 molecule of ATP or GTP is made via the addition of a phosphate group to


ADP or GDP

* 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.

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