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DOI 10.1007/s12013-013-9750-1
REVIEW PAPER
Abstract The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It
is the most important metabolic pathway for the energy
supply to the body. TCA is the most important central
pathway connecting almost all the individual metabolic
pathways. In this review article, introduction, regulation
and energetics of TCA cycle have been discussed. The
present study was carried out to review literature on TCA
cycle.
Keywords TCA cycle Energetics of TCA cycle
Regulation of TCA cycle Amphibolic role of TCA
cycle
Introduction
The citric acid cycle was proposed by Hans Adolf Krebs in
1937. The citric acid cycle is the primary metabolic pathway
for all the aerobic processes in an animal tissue. It is a series
of reactions that are important for the cells: C2 units or
acetyl-CoA that is derived from fats, carbohydrates and
lipids [12]. TCA cycle utilizes (indirectly) about 2/3 of the
total oxygen consumed by the body and generates about 2/3
of the total energy. The citric acid cycle is the final common
pathway for the oxidation of carbohydrate, protein and lipids. TCA plays an important role in gluconeogenesis,
transamination, deamination and lipogenesis. Oxidation of
acetyl-CoA by TCA cycle accounts for 2/3rd of total oxygen
History
Albert Szent-Gyorgyi and Hans Adolf Krebs [11] established reactions and components of TCA in 1930.
Location of TCA cycle
The enzymes of TCA cycle are located in mitochondrial
matrix [8].
Enzymes of TCA Cycle [17]
M. Akram (&)
Department of Eastern Medicine and Surgery, Faculty of
Medical and Health Sciences, The University of Poonch,
Azad Jammu and Kashmir, Pakistan
e-mail: makram_0451@hotmail.com; makram0451@gmail.com
Citrate synthase
Aconitase
Isocitrate dehydrogenase
Ketoglutarate dehydrogenase
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Succinyl-CoA synthase
Succinate dehydrogenase
Fumarase
Malate dehydrogenase
Sources of Acetyl-CoA
Acetyl-CoA is obtained from various sources including
carbohydrates in which glucose is broken down to pyruvic
acid and pyruvic acid is decarboxylated to acetyl-CoA.
Pyruvic acid is a three-carbon compound and acetyl-CoA is
a two-carbon compound. Acetyl-CoA (two-carbon compound) is the starting point for the TCA cycle. Breakdown
of acetyl-CoA is the catabolic role of TCA cycle. Jones
et al. [9] have reported the sources of acetyl-CoA for
entering the tricarboxylic acid cycle as determined by
analysis of succinate 13C isotopomers.
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There is no direct participation of oxygen in TCA. However, the cycle operates only under aerobic conditions [10].
Inhibitors of TCA
Fluoroacetate
It condenses with CoA and form fluoroacetyl-CoA. Fluoroacetyl-CoA condenses with oxaloacetate to form fluorocitrate that inhibits aconitase, as a result citrate start to
accumulate. Fonnum et al. [7] have studied the use of
fluorocitrate and fluoroacetate in the brain metabolism.
Arsenite
It inhibits alpha-ketoglutarate dehydrogenase
Malonate
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Regulation of TCA
Three enzymes namely citrate synthase, isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase regulate
citric acid cycle. Wan et al. [16] have reported the regulation of citric acid cycle by calcium.
2.
3.
Biosynthetic function
Several intermediates of this cycle take part in the formation of substances of great physiological importance. Citrate is provided to the lens of the eye, bone and the seminal
plasma. Citrate stimulates fatty acids synthesis by activating acetyl-CoA carboxylase
Conclusion
Citric acid cycle is one of the main metabolic pathways
that living cells utilize to completely oxidize biofuels to
carbon dioxide and water. The pyruvic acid formed as a
result of glycolysis is completely oxidized via this cycle.
Before pyruvic acid can enter citric acid cycle, it is converted to acetyl-CoA. The acetyl-CoA thus produced is
then completely oxidized in citric acid cycle. This cycle not
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