Citric Acid Cycle - Overview

Overview

The citric acid cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy. Through catabolism of sugars, fats, and proteins, a two carbon organic product acetate in the form of acetyl-CoA is produced. Acetyl-CoA along with two equivalents of water (H₂O) are consumed by the citric acid cycle producing two equivalents of carbon dioxide (CO₂) and one equivalent of HS-CoA. In addition, one complete turn of the cycle converts three equivalents of nicotinamide adenine dinucleotide (NAD+) into three equivalents of reduced NAD+ (NADH), one equivalent of ubiquinone (Q) into one equivalent of reduced ubiquinone (QH₂), and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (P_i) into one equivalent of guanosine triphosphate (GTP). The NADH and QH₂ generated by the citric acid cycle are in turn used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP).

One of the primary sources of acetyl-CoA is sugars that are broken down by glycolysis to produce pyruvate that in turn is decarboxylated by the enzyme pyruvate dehydrogenase generating acetyl-CoA according to the following reaction scheme:

• CH₃C(=O)C(=O)O– (pyruvate) + HSCoA + NAD+ → CH₃C(=O)SCoA (acetyl-CoA) + NADH + H+ + CO₂

The product of this reaction, acetyl-CoA, is the starting point for the citric acid cycle. Below is a schematic outline of the cycle:

• The citric acid cycle begins with the transfer of a two-carbon acetyl group from acetyl-CoA to the four-carbon acceptor compound (oxaloacetate) to form a six-carbon compound (citrate).
• The citrate then goes through a series of chemical transformations, losing two carboxyl groups as CO₂. The carbons lost as CO₂ originate from what was oxaloacetate, not directly from acetyl-CoA. The carbons donated by acetyl-CoA become part of the oxaloacetate carbon backbone after the first turn of the citric acid cycle. Loss of the acetyl-CoA-donated carbons as CO₂ requires several turns of the citric acid cycle. However, because of the role of the citric acid cycle in anabolism, they may not be lost, since many TCA cycle intermediates are also used as precursors for the biosynthesis of other molecules.
• Most of the energy made available by the oxidative steps of the cycle is transferred as energy-rich electrons to NAD+, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced.
• Electrons are also transferred to the electron acceptor Q, forming QH₂.
• At the end of each cycle, the four-carbon oxaloacetate has been regenerated, and the cycle continues.