Page 171 - Color Atlas of Biochemistry

162 Metabolism

Overview coenzyme andATP derivedfrom itbyoxida-
tive phosphorylation. If acetyl CoA production
exceeds the energy requirements of the hepa-
A. Fat metabolism
tocytes—as is the case when there is a high
Fat metabolism in adipose tissue (top). Fats level of fatty acids in the blood plasma (typical
(triacylglycerols) are the most important en- in hunger and diabetes mellitus)—then the
ergy reserve in the animal organism. They are excess is converted into ketone bodies (see
mostly stored in insoluble form in the cells of p. 312). These serve exclusively to supply
adipose tissue—the adipocytes—where they other tissues with energy.
are constantly being synthesized and broken
down again. Fat synthesis in the liver (right). Fatty acids
andfatsare mainly synthesizedin the liver
As precursors for the biosynthesis of fats and in adipose tissue, aswell asin the kid-
(lipogenesis), the adipocytes use triacylgly- neys, lungs, and mammary glands. Fatty acid
cerols from lipoproteins (VLDLs and chylomi- biosynthesis occurs in the cytoplasm—in con-
crons; see p. 278), which are formed in the trast to fatty acid degradation. The most im-
liver and intestines and delivered by the portant precursor is glucose,but certain
blood. Lipoprotein lipase [1], which is located aminoacids can alsobe used.
on the inner surface of the blood capillaries, The first step is carboxylation of acetyl CoA
cleaves these triacylglycerols into glycerol to malonyl CoA. Thisreaction iscatalyzed by
and fatty acids, which are taken up by the acetyl-CoA carboxylase [5], which is the key
adipocytes and converted back into fats. enzyme in fatty acid biosynthesis. Synthesis
The degradation of fats (lipolysis) is cata- into fatty acids is carried out by fatty acid
lyzed in adipocytes by hormone-sensitive synthase [6]. This multifunctional enzyme
lipase [2]—an enzyme that is regulated by (see p. 168) starts with one molecule of ace-
various hormones by cAMP-dependent inter- tyl-CoA and elongates it by adding malonyl
conversion (see p. 120). The amount of fatty groups in seven reaction cycles until palmi-
acids released depends on the activity of this tate is reached. One CO 2 molecule is released
lipase; in this way, the enzyme regulates the in each reaction cycle. The fatty acid therefore
plasma levels of fatty acids. growsbytwo carbon unitseach time.
In the blood plasma, fatty acids are trans- NADPH+H + is used as the reducing agent
ported in free form—i. e., non-esterified. Only and is derived either from the pentose phos-
short-chain fatty acids are soluble in the phate pathway (see p. 152) or from isocitrate
blood; longer, less water-soluble fatty acids dehydrogenase and malic enzyme reactions.
are transported bound to albumin. The elongation of the fatty acid by fatty acid
synthase concludes at C 16 ,and theproduct,
Degradation of fatty acids in the liver (left). palmitate (16:0), is released. Unsaturated
Many tissues take up fatty acids from the fatty acids and long-chain fatty acids can arise
blood plasma in order to synthesize fats or from palmitate in subsequent reactions. Fats
to obtain energy by oxidizing them. The me- are finally synthesized from activated fatty
tabolism of fatty acids is particularly intensive acids (acyl CoA) and glycerol 3-phosphate
in the hepatocytes in the liver. (see p. 170). To supply peripheral tissues,
The most important process in the degra- fats are packed by the hepatocytes into lipo-
dation of fatty acids is E-oxidation—a meta- protein complexes of the VLDL type and re-
bolic pathway in the mitochondrial matrix leased into the blood in this form (see p. 278).
(see p. 164). Initially, the fatty acids in the
cytoplasm are activated by binding to coen-
zyme A into acyl CoA [3]. Then, with the help
of a transport system (the carnitine shuttle
[4]; seep. 164), theactivated fattyacids enter
the mitochondrial matrix, where they are
brokendowninto acetyl CoA.The resulting
acetyl residues can be oxidized to CO 2 in the
tricarboxylic acid cycle, producing reduced

Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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