This step in carbohydrate metabolism occurs inside the mitochondria and is important because it irreversibly funnels pyruvate (C3) into the citric acid cycle. The net reaction is:
It is a complex reaction requiring pyruvate dehydrogenase (an enzyme complex composed of three different types of enzyme) and several co-factors (including TPP and NAD). This key reaction is subject to feedback control, in which the presence of high levels of energy in the form of NADH, ATP and acetyl-CoA 'switch off1 the pyruvate dehydrogenase complex. There is, thus, a net energy gain in this step of NADH, which can be converted to ATP through oxidative phosphorylation.
The citric acid cycle and oxidative phosphorylation process both form the core of the energy producing machinery in metabolism. They take place in the mitochondria and are not exclusive to carbohydrate metabolism, but form a common end pathway for the products of carbohydrate, lipid and protein metabolism. Carbohydrate metabolism and the breakdown of lipids feed acetyl-CoA into the cycle, while protein metabolism can feed into the cycle via several intermediates, including oxaloacetate (C4), a-ketoglutarate (C5) and fumarate (C4).
The main entry to the citric acid cycle is via acetyl-CoA, which is essentially an activated C2 (acetyl) group bound to a carrier (Co-enzyme A). This C2 fragment is loaded onto a C4 molecule (oxaloacetate) to form citrate (C6), which passes around a cycle of intermediate compounds. Two decarboxylation reactions take place to regenerated the oxaloacetate (C4). Energy production from each cycle is in the form of:
• One high energy phosphoryl bond in guanosine triphosphate (GTP)
The NADH and FADH2 are high potential electron carriers and enter the oxidative phosphorylation process to generate ATP (Figure MT.10).
Oxidative phosphorylation is a biochemical process in the mitochondria in which ATP is generated by the high potential electrons carried by NADH and FADH2. 'High potential' refers to the tendency for electrons to be transferred from these activated carriers to a cascade of 'lower potential' carriers (NADH-Q reductase, cytochrome reductase and cytochrome oxidase) which are located in the inner mitochondrial membrane, and are sometimes referred to as 'the respiratory chain'.
These mitochondrial membrane carriers are basically proton pumps activated by the flow of electrons through them. They pump H+ out of the inner mitochondrion to give an H+ gradient across the inner membrane. This H+ gradient then generates ATP by driving H+ back across the inner membrane through channels of ATP synthase. The passage of H+ through these channels catalyses the synthesis of ATP (Figure MT.11).
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