4. ENERGY-RICH COMPOUNDS
109
the cell during in vitro storage is directly correlated to the level of
endogenous ATP and other phosphate compounds (4).
B. PHOSPHORYLATED COMPOUNDS AND THEIR ROLE IN ENERGY STORAGE
Throughout the 1800's and early 1900's, the study of living systems
was confined, almost of necessity, to an analysis of constituent substances. Carbon, hydrogen, oxygen, and nitrogen were identified as key
elements in biological substances, and shortly thereafter the widespread
occurrence of phosphorus was noted. In 1847 Liebig (5) isolated from
mammalian muscle a crystalline material which was subsequently identified as inosinic acid (inosine-5-phosphate). However, many years intervened between this discovery and Miescher's monumental studies
in 1869 on the isolation and partial characterization of nucleic acid
(6). The 1920's and 1930's witnessed the isolation of other naturally
occurring phosphate esters [e.g., ATP (1929), DPN (1936), cliphosphothiamine (1937), flavin adenine dinucleotide (1938), and various
hexose phosphates].
Work from Meyerhofs laboratory in the 1930's drew attention to
the synthesis of ATP during glycolysis, and also to the requirement for
this compound and phosphocreatine in the process of muscle contraction. Meyerhof first measured, by calorimetric techniques, the AH of
hydrolysis for a number of biologically important phosphate esters and
anhydrides (Eq. 3):
O
O
II
II
HO—P—OR + H 2 0 ^ HO—P—OH + ROH
(3)
I
I
OH
OH
From these measurements, and from AF determinations, Meyerhof
recognized that certain phosphate esters or anhydrides possessed "energy-rich" bonds, whose hydrolysis was characterized by AF and ΔΗ
values of —8 to —12 kcal./mole. We shall see subsequently, however,
that these values were uniformly high by about 4 kcal./mole.
The concept of "energy-rich" phosphate bonds was developed more
fully in the reviews of Lipmann (7) and Kalckar (8). These authors
drew attention to ADP, phosphocreatine, phosphoarginine, acetyl phosphate, phosphoenolpyruvate, and glyceryl phosphate as additional members of the "energy-rich" category. By contrast, most of the common
phosphorylated compounds, such as glucose-6-phosphate, inositol phosphate, or choline phosphate, were shown to contain "energy-poor" phosphate linkages, which yielded only 2-4 kcal./mole upon hydrolysis.
More recently, other "energy-rich" compounds not involving a phos-
109
the cell during in vitro storage is directly correlated to the level of
endogenous ATP and other phosphate compounds (4).
B. PHOSPHORYLATED COMPOUNDS AND THEIR ROLE IN ENERGY STORAGE
Throughout the 1800's and early 1900's, the study of living systems
was confined, almost of necessity, to an analysis of constituent substances. Carbon, hydrogen, oxygen, and nitrogen were identified as key
elements in biological substances, and shortly thereafter the widespread
occurrence of phosphorus was noted. In 1847 Liebig (5) isolated from
mammalian muscle a crystalline material which was subsequently identified as inosinic acid (inosine-5-phosphate). However, many years intervened between this discovery and Miescher's monumental studies
in 1869 on the isolation and partial characterization of nucleic acid
(6). The 1920's and 1930's witnessed the isolation of other naturally
occurring phosphate esters [e.g., ATP (1929), DPN (1936), cliphosphothiamine (1937), flavin adenine dinucleotide (1938), and various
hexose phosphates].
Work from Meyerhofs laboratory in the 1930's drew attention to
the synthesis of ATP during glycolysis, and also to the requirement for
this compound and phosphocreatine in the process of muscle contraction. Meyerhof first measured, by calorimetric techniques, the AH of
hydrolysis for a number of biologically important phosphate esters and
anhydrides (Eq. 3):
O
O
II
II
HO—P—OR + H 2 0 ^ HO—P—OH + ROH
(3)
I
I
OH
OH
From these measurements, and from AF determinations, Meyerhof
recognized that certain phosphate esters or anhydrides possessed "energy-rich" bonds, whose hydrolysis was characterized by AF and ΔΗ
values of —8 to —12 kcal./mole. We shall see subsequently, however,
that these values were uniformly high by about 4 kcal./mole.
The concept of "energy-rich" phosphate bonds was developed more
fully in the reviews of Lipmann (7) and Kalckar (8). These authors
drew attention to ADP, phosphocreatine, phosphoarginine, acetyl phosphate, phosphoenolpyruvate, and glyceryl phosphate as additional members of the "energy-rich" category. By contrast, most of the common
phosphorylated compounds, such as glucose-6-phosphate, inositol phosphate, or choline phosphate, were shown to contain "energy-poor" phosphate linkages, which yielded only 2-4 kcal./mole upon hydrolysis.
More recently, other "energy-rich" compounds not involving a phos-