of the TCA cycle and oxidative phosphorylation to produce it because of
decreased oxygen tension or heavy exercise.
Glycolysis: The biochemical process by which glucose is converted to
pyruvate in the cytosol of the cell. It results in the production of 2 mol
of adenosine triphosphate (ATP) and 2 mol of the reduced cofactor
nicotinamide adenine dinucleotide (NADH), which transfers its reduc-
ing equivalents to the mitochondrion for the production of ATP via
oxidative phosphorylation.
Krebs cycle: Citric acid cycle, TCA cycle, the mitochondrial process by
which acetyl groups from acetyl-CoA are oxidized to CO2. The reduc-
ing equivalents are captured as NADH and FADH2, which feed into the
electron transport system of the mitochondrion to produce ATP via
oxidative phosphorylation.
Most of the energy that the body requires for maintenance, work, and growth
is obtained by the terminal oxidation of acetyl coenzyme A (acetyl-CoA)
that is produced by the catabolism of carbohydrates, fatty acids, and
amino acids. The oxidation of acetyl-CoA is achieved by mitochondrial
enzymes that make up the tricarboxylic acid cycle (TCA cycle, also called
the citric acid cycle or the Krebs cycle). All of the enzymes in this metabolic
pathway are located in the matrix of the mitochondria except one, succi-
nate dehydrogenase. Succinate dehydrogenase is a membrane-bound pro-
tein located on the inner mitochondrial membrane facing the matrix. The
two carbons that enter the TCA cycle as an acetyl group are effectively oxi-
dized to carbon dioxide. Oxygen is not directly involved in this process;
instead, reducing equivalents are captured by the electron carriers NAD+ and
FAD producing three (NADH + H+) and one FADH2. A high-energy phosphate
bond is also produced in the form of GTP. The reduced cofactors NADH and
FADH2 are then reoxidized by passing their reducing equivalents to O2through
the electron transport system (ETS) of the mitochondria with the production
of water and ATP via oxidative phosphorylation.
The TCA cycle is shown in Figure 14-1. In the first step, acetyl-CoA is
condensed with oxaloacetate to produce citrate with the release of free coen-
zyme A in a reaction catalyzed by citrate synthase. Citrate is then isomerized
to isocitrate by the enzyme aconitase. The next step involves the oxidative
decarboxylation of isocitrate to produce a-ketoglutarate. The enzyme cat-
alyzing this reaction, isocitrate dehydrogenase (IDH) requires the oxidized
electron carrier NAD+ to accept the electrons released in the oxidation
and produce the first NADH + H+. a-Ketoglutarate is then converted to
succinyl-CoA in a second oxidative decarboxylation reaction catalyzed by
a-ketoglutarate dehydrogenase (a-KGDH). This reaction requires the partic-
ipation of two cofactors, oxidized NAD+ and CoA, and results in the production
of a second NADH + H+. Succinyl-CoA is then transformed to succinate by
previous page 147 Case Files   Biochemistry read online next page 149 Case Files   Biochemistry read online Home Toggle text on/off