9. SACCHARIDES: ALTERNATE ROUTES OF METABOLISM
429
graph. That these discoveries did not evoke more widespread interest
at the time was probably due to at least three major factors, (a) Adequate methods for detecting the various sugar phosphates that are intermediates in the pentose cycle were not yet available, hence additional
steps in the process went undetected, (b) Most of the components steps
in the Krebs cycle were already known, so that when the Krebs cycle
was described it could immediately be tested in a variety of ways.
When this was done in many types of tissues during the 1940's, the
enzymes of the Krebs cycle were found to be both widespread and
abundant. The localizing of these enzymes in the mitochondria (8),
and the description of the mitochondria by Claude as the "intracellular
power plant" of the cell, placed the citric acid cycle in a position of
prominence as a terminal oxidation mechanism, (c) The production of
ribose phosphate by the Zwischenferment enzyme of Warburg seemed
to provide a happy solution to the question of the origin of pentose for
RNA synthesis. Despite fairly clear statements that a new scheme
might exist for the oxidation of glucose which was different from
glycolysis or the Krebs cycle (9, JO) these suggestions appear to have
had little influence at the time. Several people were working in the
field during the period 1938-1951, but the fate of triose phosphate was
clouded; it seemed possible that it could be removed as formed via
oxidation by the Krebs cycle, as if in a "shunt" mechanism; indeed, the
term "hexose monophosphate shunt" became a popular name for the
oxidation of 6-phosphogluconate. It was only after the recognition that
two moles of pentose phosphate combine to form a mole of sedoheptulose phosphate (11) and that the triose phosphate formed was
not oxidized but was probably trapped as pentose, sedoheptulose, or
hexose phosphate (12), that the complexities of the new mechanism
became appreciated by large numbers of biochemists. The work of
Horecker (1) and Racker (2) and their respective colleagues presented
the pathway in its true identity, as an independent cycle, in which under
certain circumstances glucose could be oxidized completely to carbon
dioxide and water without reference to either glycolysis or the Krebs
cycle. Others have contributed significant information that assisted in
establishing the pentose cycle; these are discussed in the reviews referred to earlier (2, 3). Still others have contributed to the general
recognition of the importance of the pentose cycle in nature; some of
these will be referred to in the pages that follow.
B. OUTLINE OF THE PENTOSE CYCLE
Respiration via the pentose cycle is outlined in Fig. 1. For convenience, six molecules of glucose-6-phosphate (G-6-P) are taken to
429
graph. That these discoveries did not evoke more widespread interest
at the time was probably due to at least three major factors, (a) Adequate methods for detecting the various sugar phosphates that are intermediates in the pentose cycle were not yet available, hence additional
steps in the process went undetected, (b) Most of the components steps
in the Krebs cycle were already known, so that when the Krebs cycle
was described it could immediately be tested in a variety of ways.
When this was done in many types of tissues during the 1940's, the
enzymes of the Krebs cycle were found to be both widespread and
abundant. The localizing of these enzymes in the mitochondria (8),
and the description of the mitochondria by Claude as the "intracellular
power plant" of the cell, placed the citric acid cycle in a position of
prominence as a terminal oxidation mechanism, (c) The production of
ribose phosphate by the Zwischenferment enzyme of Warburg seemed
to provide a happy solution to the question of the origin of pentose for
RNA synthesis. Despite fairly clear statements that a new scheme
might exist for the oxidation of glucose which was different from
glycolysis or the Krebs cycle (9, JO) these suggestions appear to have
had little influence at the time. Several people were working in the
field during the period 1938-1951, but the fate of triose phosphate was
clouded; it seemed possible that it could be removed as formed via
oxidation by the Krebs cycle, as if in a "shunt" mechanism; indeed, the
term "hexose monophosphate shunt" became a popular name for the
oxidation of 6-phosphogluconate. It was only after the recognition that
two moles of pentose phosphate combine to form a mole of sedoheptulose phosphate (11) and that the triose phosphate formed was
not oxidized but was probably trapped as pentose, sedoheptulose, or
hexose phosphate (12), that the complexities of the new mechanism
became appreciated by large numbers of biochemists. The work of
Horecker (1) and Racker (2) and their respective colleagues presented
the pathway in its true identity, as an independent cycle, in which under
certain circumstances glucose could be oxidized completely to carbon
dioxide and water without reference to either glycolysis or the Krebs
cycle. Others have contributed significant information that assisted in
establishing the pentose cycle; these are discussed in the reviews referred to earlier (2, 3). Still others have contributed to the general
recognition of the importance of the pentose cycle in nature; some of
these will be referred to in the pages that follow.
B. OUTLINE OF THE PENTOSE CYCLE
Respiration via the pentose cycle is outlined in Fig. 1. For convenience, six molecules of glucose-6-phosphate (G-6-P) are taken to