Tricarboxylic Acid Cycle(TCA)
TCA cycle was first elucidated by Sir Hans Adolf Krebs, a German Biochemist in 1937. It is also known as Tricarboxylic acid cycle, Citric acid cycle or Amphibolic cycle. In prokaryotic cells, the citric acid cycle occurs in the cytoplasm; in eukaryotic cells it takes place in the matrix of the mitochondria.
The process oxidizes glucose derivatives, fatty acids, and amino acids to carbon dioxide (CO2) through a series of enzyme controlled steps. The purpose of the Krebs cycle is to collect high energy electrons from these fuels by oxidizing them, which are transported by activated electron carriers such as NADH and FADH2 to electron transport chain. The Krebs cycle is also the source for the precursor of many other molecules and is therefore an amphibolic pathway (both anabolic and catabolic reactions take place in this cycle) and therefore, it can be used for both the synthesis and degradation of bio molecules.
Pyruvate + CoA-SH + NAD+ ←Pyruvate dehydrogenase complex→ Acetyl CoA + Co2 + NADH
Pyruvate cannot enter the Krebs cycle directly. In a preparatory step, it must lose one molecule of CO2 and becomes a two-carbon compound. This process is called decarboxylation. The two-carbon compound, called acetyl group, attaches to coenzyme A through a high-energy bond, the resulting is a complex known as acetyl coenzyme (acetyl CoA). During this reaction, pyruvic acid is also oxidized and NAD+ is reduced to NADH by pyruvate dehydrogenase complex (PDHC). This multi enzyme complex is responsible for the conversion of pyruvate to acetyl-coA. Therefore PDHC contribute to linking the Glycolysis pathway to the citric acid pathway
Pyruvate dehydroge- nase deficiency is a common cause of lactic acidosis in new born and often present with poor feeding
The Krebs cycle generates a pool of chemical energy (ATP, NADH, and FADH 2) from the oxidation of Pyruvic acid and it loses one carbon atom as CO2 and reduces NAD+ to NADH. The resulting two carbon acetyl molecule is joined to Co enzyme A. Acetyl CoA transfers its acetyl group to a 4C compound (oxaloactate) to make a 6C compound (Citrate) and the Coenzyme A is released which goes back to the link reaction to form another molecule of acetyl CoA. Oxaloacetate is both the first reactant and the product of the metabolic pathway (creating a loop).
After citrate has been formed, the cycle machinery continues through seven distinct enzyme catalyzed reactions that produce in order isocitrate, α – ketoglutarate, succinyl CoA, succinate, fumarate, malate and oxaloacetate.
At the end of Krebs cycle, each pyruvic acid produces 2 CO2, 1 ATP (substrate level phosphorylation), 3 NADH and 1 FADH2. Then NADH and FADH2 can be oxidized by electron transport chain to provide more ATPs