10. ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION
445
dase (9). Later studies by Keilin and Hartree (10) revealed that the
light absorption bands assigned to cytochrome a were composed of two
components, cytochrome a, previously described, and cytochrome a 3 . The
letters a x and a 2 had been assigned to two cytochromes of the a type
which were observed in bacteria (11). Cytochrome a 3 , which reacted
with CO in the ferrous state and was easily autoxidized, was considered
to be identical with cytochrome oxidase.
Many other cytochromes of the a, b, and c types have since been
described, but until recently most of these have resisted purification.
This is due to their association with the insoluble component of the cell.
With the discovery of numerous cytochromes there has developed a
great need for a more systematic nomenclature, but little progress has
been made in this direction.
It is not proposed to discuss the cytochromes themselves in more
detail. Authoritative reviews (12-16) are available and the comparative
aspects of these substances as a group are treated elsewhere in this
treatise (17).
2. Flavoproteins
In 1932 the first flavoprotein, the "old yellow enzyme," was discovered by Warburg and Christian (18). Their experiments on the role of
this enzyme in the aerobic oxidation of glucose-6-P0 4 led in turn to
studies on glucose-6-phosphate dehydrogenase and the discovery of
TPN
+ (19). Because its prosthetic group could be alternately reduced
and oxidized, the old yellow enzyme was postulated to function as a
carrier between TPNH and 0 2 . Although the reduced enzyme was oxidized by 0 2 in air, it could also be oxidized by cytochrome c at an
equal rate (20). This was the first indication that a flavoprotein might
serve as a link between the pyridine nucleotides and the cytochromes.
However, the rate of oxidation of the reduced old yellow enzyme by
either 0 2 or cytochrome was not large enough to be of physiological
significance.
In 1940 Haas et al. (21) described the isolation of a soluble cytochrome reductase which catalyzed the reduction of cytochrome c preferentially by TPNH. This enzyme reacted 10
5 times as rapidly with cytochrome c as did the old yellow enzyme. In recent years cytochrome reductases have been purified from several tissues including liver microsomes (22-24). The latter enzyme is interesting in that it catalyzes the
reduction of a microsomal cytochrome, but not cytochrome c. The
soluble cytochrome reductases contain a flavin nucleotide and may contain a metal ion in addition (25). They can utilize various dyes and
cytochrome c as acceptors, but do not react with oxygen. The reduction
445
dase (9). Later studies by Keilin and Hartree (10) revealed that the
light absorption bands assigned to cytochrome a were composed of two
components, cytochrome a, previously described, and cytochrome a 3 . The
letters a x and a 2 had been assigned to two cytochromes of the a type
which were observed in bacteria (11). Cytochrome a 3 , which reacted
with CO in the ferrous state and was easily autoxidized, was considered
to be identical with cytochrome oxidase.
Many other cytochromes of the a, b, and c types have since been
described, but until recently most of these have resisted purification.
This is due to their association with the insoluble component of the cell.
With the discovery of numerous cytochromes there has developed a
great need for a more systematic nomenclature, but little progress has
been made in this direction.
It is not proposed to discuss the cytochromes themselves in more
detail. Authoritative reviews (12-16) are available and the comparative
aspects of these substances as a group are treated elsewhere in this
treatise (17).
2. Flavoproteins
In 1932 the first flavoprotein, the "old yellow enzyme," was discovered by Warburg and Christian (18). Their experiments on the role of
this enzyme in the aerobic oxidation of glucose-6-P0 4 led in turn to
studies on glucose-6-phosphate dehydrogenase and the discovery of
TPN
+ (19). Because its prosthetic group could be alternately reduced
and oxidized, the old yellow enzyme was postulated to function as a
carrier between TPNH and 0 2 . Although the reduced enzyme was oxidized by 0 2 in air, it could also be oxidized by cytochrome c at an
equal rate (20). This was the first indication that a flavoprotein might
serve as a link between the pyridine nucleotides and the cytochromes.
However, the rate of oxidation of the reduced old yellow enzyme by
either 0 2 or cytochrome was not large enough to be of physiological
significance.
In 1940 Haas et al. (21) described the isolation of a soluble cytochrome reductase which catalyzed the reduction of cytochrome c preferentially by TPNH. This enzyme reacted 10
5 times as rapidly with cytochrome c as did the old yellow enzyme. In recent years cytochrome reductases have been purified from several tissues including liver microsomes (22-24). The latter enzyme is interesting in that it catalyzes the
reduction of a microsomal cytochrome, but not cytochrome c. The
soluble cytochrome reductases contain a flavin nucleotide and may contain a metal ion in addition (25). They can utilize various dyes and
cytochrome c as acceptors, but do not react with oxygen. The reduction