696
R. H. THOMSON
vitamin K in heart muscle preparations (302, 303), and in pig heart
mitochondria (304). [The present position on the role of vitamin K in
oxidative phosphorylation has been reviewed by Martius (305) and by
Dam and S0ndergaard (305a). For more detailed discussion of electron
transport and oxidative phosphorylation see Vols. I and V of this work.]
Whether or not vitamin K occurs in liver mitochondria, there is no
doubt that vitamin K is present in liver where it appears to function
as a coenzyme involved in the production of prothrombin and proconvertin which are essential for the coagulation of blood (305a). Its origin,
however, is still uncertain. Presumably some is exogenous, but probably
most of it is biosynthesized, in whole or in part, by intestinal bacteria.
The experiments of Martius and Esser (278) show that a polyisoprenoid
side chain can be added to a preformed 2-methylnaphthoquinone molecule in the liver, but the precise vitamin K compound(s) normally
synthesized within the animal body are not known.
III. Biogenesis of Quinones
In recent years two major routes have been recognized for the biosynthesis of aromatic compounds from carbohydrates. They account for
the formation of numerous natural products, including most of the
quinones, but there are many other compounds that do not appear to
fit into either of these schemes. For these, other modes of biogenesis
must exist.
A. SHIKIMIC ACID ROUTE
The shikimic acid pathway leading to phenylalanine, tyrosine, and
other aromatic acids is now firmly established by the studies of Davis,
Ehrensvärd, and others. [As this is discussed elsewhere in this treatise
(Vol. IV) and in several reviews (e.g., 153, 306, 307), it will not be
considered in detail here.] It was found that mutants of Escherichia
coli (and other bacteria and fungi) required several aromatic amino
acids for growth, all of which could be replaced by shikimic acid. Certain mutants accumulated shikimic acid, which could be isolated from
the culture medium; others, which introduced an enzymatic block earlier
in the reaction chain, accumulated precursors of shikimic acid. In this
way, by working back along the biosynthetic route, using mutants to
block each stage in turn, it was possible to establish the biogenetic
sequence shown. Enzymatic analysis of the early stages of the aromatic
biosynthesis showed that glucose is first transformed into C 3 and C 4
fragments which then combine to give a C 7 intermediate, followed by
cyclization to 5-dehydroquinic acid. The specific enzymes concerned in
the subsequent steps leading to shikimic acid have all been identified
by Davis et ah, but the manner of its conversion to prephenic acid is
R. H. THOMSON
vitamin K in heart muscle preparations (302, 303), and in pig heart
mitochondria (304). [The present position on the role of vitamin K in
oxidative phosphorylation has been reviewed by Martius (305) and by
Dam and S0ndergaard (305a). For more detailed discussion of electron
transport and oxidative phosphorylation see Vols. I and V of this work.]
Whether or not vitamin K occurs in liver mitochondria, there is no
doubt that vitamin K is present in liver where it appears to function
as a coenzyme involved in the production of prothrombin and proconvertin which are essential for the coagulation of blood (305a). Its origin,
however, is still uncertain. Presumably some is exogenous, but probably
most of it is biosynthesized, in whole or in part, by intestinal bacteria.
The experiments of Martius and Esser (278) show that a polyisoprenoid
side chain can be added to a preformed 2-methylnaphthoquinone molecule in the liver, but the precise vitamin K compound(s) normally
synthesized within the animal body are not known.
III. Biogenesis of Quinones
In recent years two major routes have been recognized for the biosynthesis of aromatic compounds from carbohydrates. They account for
the formation of numerous natural products, including most of the
quinones, but there are many other compounds that do not appear to
fit into either of these schemes. For these, other modes of biogenesis
must exist.
A. SHIKIMIC ACID ROUTE
The shikimic acid pathway leading to phenylalanine, tyrosine, and
other aromatic acids is now firmly established by the studies of Davis,
Ehrensvärd, and others. [As this is discussed elsewhere in this treatise
(Vol. IV) and in several reviews (e.g., 153, 306, 307), it will not be
considered in detail here.] It was found that mutants of Escherichia
coli (and other bacteria and fungi) required several aromatic amino
acids for growth, all of which could be replaced by shikimic acid. Certain mutants accumulated shikimic acid, which could be isolated from
the culture medium; others, which introduced an enzymatic block earlier
in the reaction chain, accumulated precursors of shikimic acid. In this
way, by working back along the biosynthetic route, using mutants to
block each stage in turn, it was possible to establish the biogenetic
sequence shown. Enzymatic analysis of the early stages of the aromatic
biosynthesis showed that glucose is first transformed into C 3 and C 4
fragments which then combine to give a C 7 intermediate, followed by
cyclization to 5-dehydroquinic acid. The specific enzymes concerned in
the subsequent steps leading to shikimic acid have all been identified
by Davis et ah, but the manner of its conversion to prephenic acid is