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TCA Assignment

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31 views7 pages

TCA Assignment

Uploaded by

radhika19053
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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TRICARBOXYLIC ACID CYCLE

P401,U

Bhoomi .S. Tari | SYBT O19 | 02.02.24

Page 1
INDEX

SR. NO HEADINGS PAGE NO.

1 Introduction 3

2 Steps Of TCA Cycle 4-6

3 Requirement of O2 by 6
TCA Cycle

4 Energetics Of Citric Acid 6-7


Cycle

5 Regulation Of TCA 7

6 Role Of Vitamins in TCA 7

7 References 7

Page 2
Introduction
The citric acid cycle (also known as the Krebs cycle or the
tricarboxylic acid—TCA cycle) is the most significant metabolic
mechanism for providing energy to the body. The Krebs cycle
synthesises around 65-70% of the ATP. The citric acid cycle is
essentially the oxidation of acetyl CoA to CO2 and water. This cycle
uses around two-thirds of the total oxygen utilised by the organism.
The TCA cycle is named after the fact that tricarboxylic acids (citrate,
cis aconitate, and isocitrate) participate in the beginning of the
process. The citric acid cycle is the last oxidative pathway for carbs,
lipids, and amino acids. This cycle not only generates energy but also
several intermediates used in the synthesis of amino acids, glucose,
heme, and other compounds. The Krebs cycle is the most essential
core pathway, linking nearly all of the various metabolic pathways. The
TCA cycle enzymes are positioned in the mitochondrial matrix, near to
the electron transport chain. This allows for unhindered ATP
generation via oxidative phosphorylation. The Krebs cycle consists of
combining a two-carbon acetyl CoA with a four-carbon oxaloacetate to
form a six-carbon tricarboxylic acid, citrate. In the subsequent
processes, the two carbons are converted to CO2, and oxaloacetate is
regenerated and recycled. Oxaloacetate is believed to serve a catalytic
role in the citric acid cycle. The Krebs cycle is a cyclical process.
However, it should not be considered a closed circle because various
compounds enter and exit the cycle.

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Steps of TCA Cycle
The pyruvate dehydrogenase complex's oxidative decarboxylation of
pyruvate to acetyl CoA has previously been described. This phase
connects glycolysis and the TCA cycle. However, a few writers describe
the pyruvate-to-acetyl CoA conversion as part of the citric acid cycle.

1.Formation of citrate : Krebs cycle proper starts with the


condensation of acetyl CoA and oxaloacetate, catalysed by the enzyme
citrate synthase.

2. and 3. Citrate is isomerized to isocitrate by the enzyme aconitase.


This is achieved in a two stage reaction of dehydration followed by
hydration through the formation of an intermediate—cis-aconitate.

4. and 5. Formation of D-ketoglutarate : The enzyme isocitrate


dehydrogenase (ICD) catalyses the conversion (oxidative
decarboxylation) of isocitrate to oxalosuccinate and then to D-
ketoglutarate. The formation of NADH and the liberation of CO2 occur
at this stage.

6. Conversion of D-ketoglutarate to succinyl CoA occurs through


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oxidative decarboxylation, catalysed by D-ketoglutarate dehydrogenase
complex. This enzyme is dependent on five cofactors—TPP, lipoamide,
NAD+, FAD and CoA. The mechanism of the reaction is analogous to
the conversion of pyruvate to acetyl CoA.

7. Formation of succinate : Succinyl CoA is converted to succinate by


succinate thiokinase. This reaction is coupled with the
phosphorylation of GDP to GTP. This is a substrate level
phosphorylation. GTP is converted to ATP by the enzyme nucleoside
diphosphate kinase. GTP + ADP l ATP + GDP

8. Conversion of succinate to fumarate : Succinate is oxidized by


succinate dehydrogenase to fumarate. This reaction results in the
production of FADH2 and not NADH.

9. Formation of malate : The enzyme fumarase catalyses the


conversion of fumarate to malate with the addition of H2O.

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10. Conversion of malate to oxaloacetate : Malate is then oxidized to
oxaloacetate by malate dehydrogenase. The third and final synthesis of
NADH occurs at this stage. The oxaloacetate is regenerated which can
combine with another molecule of acetyl CoA, and continue the cycle.

Requirement of O2 by TCA cycle

 There is no direct participation of oxygen in Krebs cycle. However,


the cycle operates only under aerobic conditions.
 This is due to the fact that NAD+ and FAD (from NADH and
FADH2, respectively) required for the operation of the cycle can be
regenerated in the ETC only in the presence of O2.
 Therefore, citric acid cycle is strictly aerobic in contrast to
glycolysis which operates in both aerobic and anaerobic
conditions.

Energetics of citric acid cycle

 During the process of oxidation of acetyl CoA via citric acid cycle,
4 reducing equivalents (3 as NADH and one as FADH2) are
produced.
 Oxidation of 3 NADH by electron transport chain coupled with
oxidative phosphorylation results in the synthesis of 9 ATP,
whereas FADH2 leads to the formation of 2 ATP.

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 Besides, there is one substrate level phosphorylation. Thus, a
total of twelve ATP (10 as per recent evidence) are produced from
one acetyl CoA.

Regulation of citric acid cycle

The cellular demands of ATP are crucial in controlling the rate of


citric acid cycle. The regulation is brought about either by enzymes or
the levels of ADP. Three enzymes—namely citrate synthase, isocitrate
dehydrogenase and D-ketoglutarate dehydrogenase—regulate citric
acid cycle.
1. Citrate synthase is inhibited by ATP, NADH, acetyl CoA and succinyl
CoA.
2. Isocitrate dehydrogenase is activated by ADP, and inhibited by ATP
and NADH.
3. D-Ketoglutarate dehydrogenase is inhibited by succinyl CoA and
NADH.
4. Availability of ADP is very important for the citric acid cycle to
proceed. This is due to the fact that unless sufficient levels of ADP are
available, oxidation (coupled with phosphorylation of ADP to ATP) of
NADH and FADH2 through electron transport chain stops. The
accumulation of NADH and FADH2 will lead to inhibition of the
enzymes (as stated above) and also limits the supply of NAD+ and FAD
which are essential for TCA cycle to proceed.

Role of vitamins in TCA cycle

Four B-complex vitamins are essential for Krebs cycle, and thus
energy generation
1. Thiamine (as TPP) as a coenzyme for D-ketoglutarate
dehydrogenase.
2. Riboflavin (as FAD) as a coenzyme for succinate dehydrogenase.
3. Niacin (as NAD+) as electron acceptor for isocitrate dehydrogenase,
D-ketoglutarate dehydrogenase and malate dehydrogenase.
4. Pantothenic acid (as coenzyme A) attached to active carboxylic acid
residues i.e. acetyl CoA, succinyl CoA.

References
Biochemistry by Dr. U. Satyanarayana Dr. U. Chakrapani.

Page 7

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