1. PENTOSE PHOSPHATE CYCLE
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III. Role of the Pentose Phosphate Cycle
The pentose phosphate cycle serves three purposes—the furnishing
of intermediates, reduced pyridine nucleotides, and, perhaps, energy.
Triose phosphate may be used for carbohydrate synthesis as in the case
of the carbon reduction cycle (10), pentose phosphates for the synthesis
of nucleic acids (13), tetrose phosphate for the synthesis of aromatic
amino acids via shikimic acid (14), and phosphogluconate for L-ascorbate
synthesis in plants (15). Since fatty acid synthesis is dependent on the
level of TPNH (16), the formation of fatty acids may be linked to the
oxidative pentose phosphate pathway through this mechanism (17). In
lactating mammary glands, however, fatty acid synthesis appears to
regulate this pentose phosphate cycle activity via the rate-limiting
reoxidation of TPNH (18).
As an energy source, the direct oxidative pathway may play a lesser
role than glycolysis. So far, there is no evidence for the direct coupling
of TPNH with oxidative phosphorylation (19), although TPNH can
transfer its hydrogen to diphosphopyridine nucleotide (DPN
+ ) via the
transhydrogenase reaction. Other means, however, are possible for the
formation of ATP: (a) substrate level phosphorylation of adenosine
diphosphate during the oxidation of the triose phosphate; and (b) phosphoroclastic cleavage of either fructose-6-phosphate or xylulose-5-phosphate to form acetyl phosphate (20).
IV. Brief History
A. THE OXIDATIVE PENTOSE PHOSPHATE CYCLE
The history of the oxidative pentose phosphate cycle dates back to
1931 when Warburg and Christian discovered glucose-6-phosphate dehydrogenase in red blood cells (21). Actually, there was much evidence
suggesting the existence of alternate pathways of glucose metabolism
(22, 23) as well as of pentose metabolism (24, 25) prior to this time,
but proof was not unequivocal owing to the lack of information about
the exact mechanism of the Embden-Meyerhof-Parnas scheme. In the
years following the discovery of this dehydrogenase, much effort was
devoted to the isolation and characterization of the coenzyme of the
dehydrogenase reaction, namely, triphosphopyridine nucleotide (TPN
+ )
(26). Between 1935 and 1936, a second dehydrogenase was found, this
enzyme being capable of oxidizing the product of the first dehydrogenase
reaction with a concomitant evolution of carbon dioxide (26-29).
Although a pentose phosphate was suggested as the product of this second
dehydrogenase reaction, proof was not forthcoming until two different
5
III. Role of the Pentose Phosphate Cycle
The pentose phosphate cycle serves three purposes—the furnishing
of intermediates, reduced pyridine nucleotides, and, perhaps, energy.
Triose phosphate may be used for carbohydrate synthesis as in the case
of the carbon reduction cycle (10), pentose phosphates for the synthesis
of nucleic acids (13), tetrose phosphate for the synthesis of aromatic
amino acids via shikimic acid (14), and phosphogluconate for L-ascorbate
synthesis in plants (15). Since fatty acid synthesis is dependent on the
level of TPNH (16), the formation of fatty acids may be linked to the
oxidative pentose phosphate pathway through this mechanism (17). In
lactating mammary glands, however, fatty acid synthesis appears to
regulate this pentose phosphate cycle activity via the rate-limiting
reoxidation of TPNH (18).
As an energy source, the direct oxidative pathway may play a lesser
role than glycolysis. So far, there is no evidence for the direct coupling
of TPNH with oxidative phosphorylation (19), although TPNH can
transfer its hydrogen to diphosphopyridine nucleotide (DPN
+ ) via the
transhydrogenase reaction. Other means, however, are possible for the
formation of ATP: (a) substrate level phosphorylation of adenosine
diphosphate during the oxidation of the triose phosphate; and (b) phosphoroclastic cleavage of either fructose-6-phosphate or xylulose-5-phosphate to form acetyl phosphate (20).
IV. Brief History
A. THE OXIDATIVE PENTOSE PHOSPHATE CYCLE
The history of the oxidative pentose phosphate cycle dates back to
1931 when Warburg and Christian discovered glucose-6-phosphate dehydrogenase in red blood cells (21). Actually, there was much evidence
suggesting the existence of alternate pathways of glucose metabolism
(22, 23) as well as of pentose metabolism (24, 25) prior to this time,
but proof was not unequivocal owing to the lack of information about
the exact mechanism of the Embden-Meyerhof-Parnas scheme. In the
years following the discovery of this dehydrogenase, much effort was
devoted to the isolation and characterization of the coenzyme of the
dehydrogenase reaction, namely, triphosphopyridine nucleotide (TPN
+ )
(26). Between 1935 and 1936, a second dehydrogenase was found, this
enzyme being capable of oxidizing the product of the first dehydrogenase
reaction with a concomitant evolution of carbon dioxide (26-29).
Although a pentose phosphate was suggested as the product of this second
dehydrogenase reaction, proof was not forthcoming until two different