Krebs cycle WORLD OF MICROBIOLOGY AND IMMUNOLOGY332•
(the A stands for acetylation). Coenzyme A is composed of
the RNAnucleotide adenine diphosphate, linked to a pan-
tothenate, linked to a mercaptoethylamine unit, with a termi-
nal S-H.Dehydration of this linkage with the OH of an
acetate group produces acetyl CoA. This reaction is cat-
alyzed by pyruvate dehydrogenase complex, a large multi-
enzyme complex.
The acetyl CoA linkage is weak, and it is easily and irre-
versibly hydrolyzed when Acetyl CoA reacts with the four-
carbon compound oxaloacetate. Oxaloacetate plus the acetyl
group form the six-carbon citric acid, or citrate. (Citric acid
contains three carboxylic acid groups, hence the alternate
names for the Krebs cycle.)
Following this initiating reaction, the citric acid under-
goes a series of transformations. These result in the formation
of three molecules of the high-energy hydrogen carrier NADH
(nicotinamide adenine dinucleotide), 1 molecule of another
hydrogen carrier FADH2 (flavin adenine dinucleotide), 1 mol-
ecule of high-energy GTP (guanine triphosphate), and 2 mol-
ecules of carbon dioxide, a waste product. The oxaloacetate is
regenerated, and the cycle is ready to begin again. NADH and
FADH2 are used in the final stages of cellular respirationto
generate large amounts of ATP.
As a central metabolic pathway in the cell, the rate of the
Krebs cycle must be tightly controlled to prevent too much, ortoo little, formation of products. This regulation occurs through
inhibition or activation of several of the enzymesinvolved.
Most notably, the activity of pyruvate dehydrogenase is inhib-
ited by its products, acetyl CoA and NADH, as well as by GTP.
This enzyme can also be inhibited by enzymatic addition of a
phosphate group, which occurs more readily when ATP levels
are high. Each of these actions serves to slow down the Krebs
cycle when energy levels are high in the cell. It is important to
note that the Krebs cycle is also halted when the cell is low on
oxygen, even though no oxygen is consumed in it. Oxygen is
needed further along in cell respiration though, to regenerate
NAD+ and FAD. Without these, the cycle cannot continue, and
pyruvic acid is converted in the cytosol to lactic acid by the fer-
mentationpathway.
The Krebs cycle is also a source for precursors for
biosynthesis of a number of cell molecules. For instance, the
synthetic pathway for amino acids can begin with either
oxaloacetate or alpha-ketoglutarate, while the production of
porphyrins, used in hemoglobin and other proteins, begins
with succinyl CoA. Molecules withdrawn from the cycle for
biosynthesis must be replenished. Oxaloacetate, for instance,
can be formed from pyruvate, carbon dioxide, and water, with
the use of one ATP molecule.See alsoMitochondria and cellular energywomi_K 5/6/03 3:29 PM Page 332