BIOLOGICAL SIGNIFICANCE AND ROLES OF THE KREB’S CYCLE

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Krebs cycle is the cyclic system that comprises several enzymatically catalyzed reactions that play significant biological role in the metabolic activities of living organisms inclusive of prokaryotic and eukaryotic cells. It can also be called tricarboxylic acid (TCA) cycle or citric acid cycle. Citric acid is an important metabolic intermediate in living organism; and this molecule is a tricarboxylic acid molecule that can also be found in plants especially citrus fruits. Abnormal accumulation of citric acid cycle in an organism could be due to the malfunctioning of the organism’s TCA or Kreb’s cycle. The enzymes that catalyze the TCA cycle are mainly located in the cytoplasm of both eukaryotic and prokaryotic cells. Although, these enzymes are largely located in the mitochondrion of eukaryotic cells since some of the enzymes such as succinate dehydrogenase are membrane-bound. The Kreb’s cycle is so named because of the discoverer of this important metabolic pathway who happened to be known as Hans Krebs (1900-1981).

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The TCA cycle is generally an amphibolic metabolic pathway because it can carry out both anabolic and catabolic reactions depending on the current physiological status of the cell. Some of the important intermediates of the TCA cycle include: citrate, isocitrate, succinyl CoA, succinate, fumarate, malate, α-ketoglutarate and oxaloacetate; and each of the reactions responsible for the production of each of these intermediates are catalyzed by different enzymes (Figure 1). The major biological function of the TCA cycle in living systems is in the generation of energy or ATP in corporation with the oxidative phosphorylation that occurs in the mitochondrion of the cell. In the TCA cycle, acetyl CoA recovered from the breakdown of glucose, lipids or proteins are oxidized to form carbondioxide (CO2) and ATP.

Figure 1. Illustration of Kreb cycle.

The TCA cycle is mainly catalyzed by eight (8) different enzymes including: citrate synthetase (which catalyzes the condensation of acetyl CoA with oxaloacetate to produce citrate); aconitase (which catalyzes the isomerization of citrate to isocitrate); isocitrate dehydrogenase (which catalyzes the oxidation of isocitrate to α-ketoglutarate); α-ketoglutarate dehydrogenase (which catalyzes the oxidation of α-ketoglutarate to succinyl CoA); succinyl CoA synthetase (which catalyzes the conversion of succinyl CoA to succinate); succinate dehydrogenase (which catalyzes the oxidation of succinate to fumarate); fumarase (which catalyzes the hydration of fumarate to malate); and finally malate dehydrogenase (which catalyzes the oxidation of malate to oxaloacetate). The formation of oxaloacetate via the oxidation of malate by malate dehydrogenase marks the completion of the TCA cycle; and the cycle continues from here again.     

In the Kreb’s cycle, much more energy is produced when pyruvate is degraded aerobically to CO2; and this occurs in the TCA cycle. Acetyl CoA is the starting molecule or substrate for the TCA cycle; and it is produced from the oxidation or breakdown of pyruvate (the end product of the glycolytic pathway). In eukaryotic cells, the acetyl CoA produced from the breakdown of pyruvate enters the TCA cycle in the mitochondrion while in prokaryotes; the acetyl CoA enters the bacterial or prokaryotic cytosol or cytoplasm. Citric acid is of immense industrial importance because it is used to produce a wide variety of products aside their significant health benefits. Aspergillus niger is one important microbe (a fungal mould in particular) from which citric acid can be sourced from industrially. Citric acid can be used as antioxidants; and they are important component of most beverages especially drinks.

FURTHER READING

Alberts B, Bray D, Lewis J, Raff M, Roberts K and Watson J.D (2002). The molecular Biology of the Cell. Fourth edition. New York, Garland, USA.

Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts: Pearson Prentice Hall.

Cooper G.M and Hausman R.E (2004). The cell: A Molecular Approach. Third edition. ASM Press.

Karp, Gerald (2009). Cell and Molecular Biology: Concepts and Experiments. John Wiley & Sons.

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of microorganisms. 12th edition. Pearson Benjamin Cummings Publishers. USA. Pp.795-796.

Nelson, David L.; Cox, Michael M. (2005). Lehninger Principles of Biochemistry (4th ed.). New York: W.H. Freeman.

Verma P.S and Agarwal V.K (2011). Cytology: Cell Biology and Molecular Biology. Fourth edition. S. Chand and Company Ltd, Ram Nagar, New Delhi, India.

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