3. LIPIDS: STEROID METABOLISM
167
Squalene
Cholesterol
Zymosterol
(XIII)
Desmosterol
(XIV)
FIG. lb. Reaction sequence showing substances which may be intermediates in
the biosynthesis of cholesterol from squalene.
molecule, supporting the view that mevalonic acid forms an "isoprene
unit" six of which condense to form the C 30 squalene. A similar distribution of isotope was found in cholesterol prepared biosynthetically
from 2-C
14 -mevalonate (17). It seems clear from present evidence (18)
that mevalonic acid can serve as the direct source of the isoprenoid
units for the biosynthesis of squalene and cholesterol.
Little is known of the biosynthesis of mevalonic acid other than the
facts that it is formed during yeast alcohol fermentation and enzymes
have been found in yeast which transform ß-hydroxy-ß-methylglutaryl
coenzyme A (IV) to mevalonic acid. There is, however, no evidence
that the coenzyme A derivative is a natural precursor of mevalonic
acid. Mevalonic acid formation has not been detected during squalene
or sterol biosynthesis by mammalian tissues possibly because of the
efficiency with which it is transformed to other substances. If this is
indeed the case, the formation of mevalonic acid must be severely rate
167
Squalene
Cholesterol
Zymosterol
(XIII)
Desmosterol
(XIV)
FIG. lb. Reaction sequence showing substances which may be intermediates in
the biosynthesis of cholesterol from squalene.
molecule, supporting the view that mevalonic acid forms an "isoprene
unit" six of which condense to form the C 30 squalene. A similar distribution of isotope was found in cholesterol prepared biosynthetically
from 2-C
14 -mevalonate (17). It seems clear from present evidence (18)
that mevalonic acid can serve as the direct source of the isoprenoid
units for the biosynthesis of squalene and cholesterol.
Little is known of the biosynthesis of mevalonic acid other than the
facts that it is formed during yeast alcohol fermentation and enzymes
have been found in yeast which transform ß-hydroxy-ß-methylglutaryl
coenzyme A (IV) to mevalonic acid. There is, however, no evidence
that the coenzyme A derivative is a natural precursor of mevalonic
acid. Mevalonic acid formation has not been detected during squalene
or sterol biosynthesis by mammalian tissues possibly because of the
efficiency with which it is transformed to other substances. If this is
indeed the case, the formation of mevalonic acid must be severely rate