Page 147 - Color Atlas of Biochemistry
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138 Metabolism
Tricarboxylic acid cycle: functions carboxylase [1]. It allows pyruvate yielding
amino acids and lactate to be used for gluco-
neogenesis.
A. Tricarboxylic acid cycle: functions
By contrast, acetyl CoA does not have ana-
The tricarboxylic acid cycle (see p. 136) is plerotic effects in animal metabolism. Its car-
often described as the “hub of intermediary bonskeletoniscompletely oxidized toCO 2
metabolism.” It has both catabolic and ana- and is therefore no longer available for bio-
bolic functions—it is amphibolic. synthesis. Since fatty acid degradation only
As a catabolic pathway, it initiates the “ter- supplies acetylCoA,animals areunableto
minal oxidation” of energy substrates. Many convert fatty acids into glucose. During peri-
catabolic pathways lead to intermediates of ods of hunger, it is therefore not the fat re-
the tricarboxylic acid cycle, or supply metab- serves that are initially drawn on, but pro-
olites such as pyruvate and acetyl-CoA that teins. In contrast to fatty acids, the amino
can enter the cycle, where their C atoms are acids released are able to maintain the blood
oxidized to CO 2 . The reducing equivalents glucose level (see p. 308).
(see p. 14) obtained in this way are then
used for oxidative phosphorylation—i. e., to The tricarboxylic acid cycle not only takes
aerobically synthesize ATP (see p. 122). up acetyl CoA from fatty acid degradation, but
also supplies the material for the biosynthesis
The tricarboxylic acid cycle also supplies of fatty acids and isoprenoids. Acetyl CoA,
important precursors for anabolic pathways. which is formed in the matrix space of mito-
Intermediates in the cycle are converted into: chondria by pyruvate dehydrogenase (see
p. 134), is not capable of passing through the
• Glucose (gluconeogenesis; precursors: oxa- inner mitochondrial membrane. The acetyl
loacetate and malate—see p. 154)
• Porphyrins (precursor: succinyl-CoA—see residue is therefore condensed with oxalo-
acetate by mitochondrial citrate synthase to
p. 192)
• Amino acids (precursors: 2-oxoglutarate, form citrate. This then leaves the mitochon-
dria by antiport with malate (right; see
oxaloacetate—see p. 184) p. 212). In the cytoplasm, it is cleaved again
• Fatty acids and isoprenoids (precursor: cit- by ATP-dependent citrate lyase [4] into acetyl-
rate—see below)
CoA and oxaloacetate. The oxaloacetate
Theintermediates of thetricarboxylic acid formed is reduced by a cytoplasmic malate
cycle are present in the mitochondria only in dehydrogenase to malate [2], which then re-
very small quantities. After the oxidation of turns to the mitochondrion via the antiport
acetyl-CoA to CO 2 , they are constantly regen- already mentioned. Alternatively, the malate
erated, and their concentrations therefore re- can be oxidized by “malic enzyme” [5], with
main constant, averaged over time. Anabolic decarboxylation, to pyruvate. The NADPH+H +
pathways, which remove intermediates of the formed in this process is also used for fatty
cycle (e. g., gluconeogenesis) would quickly acid biosynthesis.
use up the small quantities present in the
mitochondria if metabolites did not reenter Additional information
the cycle at other sites to replace the com-
pounds consumed. Processes that replenish Using the so-called glyoxylic acid cycle,plants
the cycle in this way are called anaplerotic and bacteria are able to convert acetyl-CoA
reactions. into succinate, which then enters the tricar-
The degradation of most amino acids is boxylic acid cycle. For these organisms, fat
anaplerotic, because it produces either inter- degradation therefore functions as an ana-
mediates of the cycle or pyruvate (glucogenic plerotic process. In plants, this pathway is
amino acids; see p. 180). Gluconeogenesis is in located in special organelles, the glyoxysomes.
fact largely sustained by the degradation of
amino acids. A particularly important ana-
plerotic step in animal metabolism leads
from pyruvate to oxaloacetic acid. This ATP-
dependent reaction is catalyzed by pyruvate
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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