Scribd
Upload
9 views

TCA Cycle

The Tricarboxylic Acid (TCA) cycle, also known as the Citric Acid or Krebs Cycle, is the primary pathway for the oxidation of carbohydrates, amino acids, and fatty acids, resulting in the production of CO2, H2O, and ATP. It occurs in the mitochondrial matrix and plays a crucial role in energy production and various metabolic processes such as gluconeogenesis and lipogenesis. Key enzymes and coenzymes are involved in the cycle, and deficiencies, such as pyruvate dehydrogenase deficiency, can lead to severe clinical consequences.

Uploaded by

Bshar Ali Zain
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
9 views

TCA Cycle

The Tricarboxylic Acid (TCA) cycle, also known as the Citric Acid or Krebs Cycle, is the primary pathway for the oxidation of carbohydrates, amino acids, and fatty acids, resulting in the production of CO2, H2O, and ATP. It occurs in the mitochondrial matrix and plays a crucial role in energy production and various metabolic processes such as gluconeogenesis and lipogenesis. Key enzymes and coenzymes are involved in the cycle, and deficiencies, such as pyruvate dehydrogenase deficiency, can lead to severe clinical consequences.

Uploaded by

Bshar Ali Zain
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
You are on page 1/ 33

Tricarboxylic Acid Cycle (TCA)

Citric Acid Cycle

Krebs Cycle

(Catabolism of Acetyl-CoA)
Definition:
• TCA cycle is the final pathway of
oxidation of carbohydrates, amino acids,
and fatty acids giving CO2, H2O and ATPs.
• The cycle is the major pathway for the
formation of ATPs
Location of TCA
• Located in the matrix of mitochondria
• Adjacent to the enzymes of the
respiratory chain and oxidative
phosphorylation.
TCA cycle is Amphibolic
• TCA important for oxidation and
production of ATPs and CO2 , it is
important for :

 Gluconeogenesis
 Lipogenesis fatty acid synthesis

Interconversion of amino acids


Organs that take on TCA

• TCA takes place in many tissues


that contains mitochondrea , but
the liver is the most tissue in which
it occurs to a significant extent.
Oxidation of pyruvate
• Pyruvate is oxidatively decarboxalated
by pyruvate dehydrogenase complex
enzyme, producing acetyl CoA
• Acetyl CoA is the main substrate for the
tricarboxylic acid cycle (TCA cycle).
• The enzyme pyruvate dehydrogenase
complex requires five coenzymes:
 Thiamine pyrophosphate

lipoic acid

 FAD

 NAD

 Coenzyme A
• The the oxidation of pyrovate by by
pyrovate dehydrogease complex is inhibited
by:
 ATP
Acetyl CoA
NADH
 Calcium.
Oxidation of Pyrovate

Pyrovate dehydrogenase complex


• Arsenic poisoning causes inactivation
of pyruvate dehydrogenase by
binding to lipoic acid.
TCA pathway
Citrate synthesis:
Citrate synthesis:

• Citrate is synthesized from oxaloacetate


(OAA) and acetyl CoA by citrate
synthase.
• This enzyme is allosterically activated by
ADP, and inhibited by ATP, NADH,
succinyl CoA, and fatty acyle CoA
derivatives
Cis aconitate formation:
Isocitrate formation:
j
J
α-ketoglutarate synthesis :
α-ketoglutarate synthesis :

• Isocitrate is oxidized and decarboxylated by


isocitrate dehydrogenase to α-
ketoglutarate, producing CO2 and
NADH+H.
• The enzyme is inhibited by ATP and
NADH+H, and activated by ADP and Ca+++.
Succinyl CoA formation
Succinyl CoA formation

• ά ketogluterate is oxidatively decarboxylated


to succinyl CoA by the α-ketoglutarate
dehydrogenase complex, producing CO2 and
NADH+H
• The enzyme is very similar to pyruvate
dehydrogenase and uses the same
coenzymes.
• a-Ketoglutarate dehydrogenase complex
is activated by calcium and inhibited by
ATP, GTP, NADH.
• The toxicity of arsenic is the result of
competition of arsenate with inorganic
phosphate (Pi) in this reaction to give 1-
arseno-3-phosphoglycerate, which hydrolyzes
spontaneously to 3-phosphoglycerate
without forming ATP.
Succinate formation
Succinate formation:

• Succinyl CoA is cleaved by succinate


thiokinase (also called succinyl CoA
synthetase), producing succinate and
GTP.
• This is an example of substrate-level
phosphorylation.
Fumerate synthesis
Fumerate synthesis:

• Succinate is oxidized to Fumerate by


succinate dehydrogenase, producing
FADH+H
• This enzyme is inhibited by oxaloacetate.
Malate fomation
Oxaloacetate synthesis
• Malate is oxidized to oxaloacetate by malate
dehydrogenase, producing NADH+H
TCA
cycle
Clinical aspects

• Pyruvate dehydrogenase
deficiency is the most common
biochemical cause of congenital
lactic acidosis
• Because the deficiency deprives the
brain of acetyl CoA, the central
nervous system is particularly
affected, with profound
psychomotor retardation and death
occurring in most patients.
Counting for ATPs
• Isocitrate dehydrogenase , producing
NADH +H= 3 ATP
• α-ketoglutarate dehydrogenase complex, producing
NADH+H = 3ATP
• succinate thiokinase produce at substrate level
phosphorylation
= 1ATP
• succinate dehydrogenase, producing
FADH+H = 2ATP
• malate dehydrogenase, producing
NADH+H = 3ATP
• Number of ATPs produced from oxidation

of Acetyl CoA in TCA= 12 ATPs

• Number of ATPs produced from

• Full oxidation of one mole of Glucose

produce ……. moles of ATPs

You might also like