Page 117 - Color Atlas of Biochemistry

P. 117

108 Metabolism

Coenzymes 3 THF derivatives in the biosynthesis of DNA
precursors, the enzymes involved in THF me-
tabolism are primary targets for cytostatic
A. Group-transferring coenzymes 2
drugs (see p. 402).
Pyridoxal phosphate (4)is the most important
coenzyme in amino acid metabolism. Its role The cobalamins (7) are the chemically most
in transamination reactions is discussed in complex form of coenzyme. They also repre-
detail on p. 178. Pyridoxal phosphate is also sent the only natural substances that contain
involved in other reactions involving amino the transition metal cobalt (Co) as an essential
acids, such as decarboxylations and dehydra- component. Higher organisms are unable to
tions. The aldehyde form of pyridoxal phos- synthesize cobalamins themselves, and are
phate shown here (left) is not generally found therefore dependent on a supply of vitamin
in free form. In the absence of substrates, the B 12 synthesized by bacteria (see p. 368).
aldehyde group is covalently bound to the ε- The central component of the cobalamins
amino group of a lysine residue as aldimine is the corrin ring, a member of the tetrapyr-
(“Schiff’s base”). Pyridoxamine phosphate roles, at the center of which the cobalt ion is
(right) is an intermediate of transamination located. The end of one of the side chains of
reactions. It reverts to the aldehyde form by the ring carries a nucleotide with the unusual
reacting with 2-oxoacids (see p. 178). base dimethylbenzimidazole. The ligands for
the metal ion are the four N atoms of the
Biotin (5)is the coenzyme of the carboxy- pyrrole ring, a nitrogen from dimethylbenzi-
lases. Like pyridoxal phosphate, it has an midazole, and a group X, which is organo-
amide-type bond via the carboxyl group metallically bound—i. e., mainly covalently.
with a lysine residue of the carboxylase. This
bond is catalyzed by a specific enzyme. Using In methylcobalamin,X is a methyl group.
ATP, biotin reacts with hydrogen carbonate This compound functions as a coenzyme for
–
(HCO 3 )to form N-carboxybiotin . From this several methyltransferases, and among other
activated form, carbon dioxide (CO 2 )is then things is involved in the synthesis of methio-
transferred to other molecules, into which a nine from homocysteine (see p. 418). How-
carboxyl group is introduced in this way. Ex- ever, in human metabolism, in which methio-
amples of biotindependent reactions of this nine is an essential amino acid, this reaction
type include the formation of oxaloacetic acid does not occur.
from pyruvate (see p. 154) and the synthesis
of malonyl-CoA from acetyl-CoA (see p. 162). Adenosylcobalamin (coenzyme B 12 )carries
a covalently bound adenosyl residue at the
Tetrahydrofolate (THF, 6)is a coenzyme metal atom. This is a coenzyme of various
that can transfer C 1 residues in different oxi- isomerases, which catalyze rearrangements
dation states. THF arises from the vitamin folic following a radical mechanism. The radical
acid (see p. 366) by double hydrogenation of arises here through homolytic cleavage of the
the heterocyclic pterin ring. The C 1 units bond between the metal and the adenosyl
being transferred are bound to N-5, N-10, or group. The most important reaction of this
both nitrogen atoms. The most important de- type in animal metabolism is the rearrange-
rivatives are: ment of methylmalonyl-CoA to form succinyl-
5
10
a) N -formyl-THF and N -formyl-THF,in CoA, which completes the breakdown of odd-
which the formyl residue has the oxidation numbered fatty acids and of the branched
state of a carboxylic acid; amino acids valine and isoleucine (see
5
b) N -methylene-THF,with a C 1 residue in pp. 166 and 414).
theoxidation stateof an aldehyde; and
5
c) N -methyl-THF,in which themethyl
group has the oxidation state of an alcohol.
C 1 units transferred by THF play a role in
the synthesis of methionine (see p. 412), pu-
rine nucleotides (see p. 188), and dTMP (see
p. 190), for example. Due to the central role of

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