3. MECHANISMS FOR FATTY ACID OXIDATION
81
however, plays no function in either plant or animal tissues, since
acetokinase and phosphotransacetylase are absent; in bacteria these
two enzymes probably play an important role in the formation and
utilization of high-energy phosphate.
In many tissues general as well as specific thiol esterases (deacylases) (18) are found which carry out the irreversible reaction:
RCO-CoA + H 2 0 -> RCOOH + CoA
(11)
The enzymes for the deacylation of succinyl-CoA and acetyl-CoA occur
in heart, liver, and bacterial extracts (19). It is of some interest to
examine the role of these deacylases in tissues. Physiologically, it is
known that in liver tissue acetoacetic acid accumulates and is metabolically inert. But in kidney or in heart tissue acetoacetic acid is
rapidly consumed. It appears that in liver a significant concentration
of an acetoacetyl-CoA deacylase occurs. Moreover ß-keto acid thiokinase (20) which catalyzes the reaction
Acetoacetic acid + CoA + ATP -> Acetoacetyl-CoA + AMP + PP
(12)
is virtually absent in liver but present in kidney and heart (21). Once
acetoacetic acid is formed by deacylation of its CoA derivative in the
liver it becomes metabolically inert. In contrast, in kidney and heart
deacylase activity is low and any circulating acetoacetic acid is rapidly
channeled by the activating enzymes into the metabolic pool (see Section II,C for further discussion).
It is obvious that the control of the concentration of these enzymes
in the cell is of considerable importance in the utilization of acyl CoA
derivatives. For example Lynen (22) observed that octanoyl-CoA thioesterase in mitochondrial preparations acts as a barrier for the synthesis
of long chain fatty acids from acetyl-CoA. Instead of accepting another
acetyl unit for long chain fatty acid synthesis octonoyl-CoA is hydrolyzed to the free acid and thus the thioesterase breaks the chain of
synthesis reactions. Another type of hydrolytic enzyme is propionyl
adenylate hydrolase, which has been found in extracts of an unidentified bacterium isolated from Massachusetts garden soil and grown on
propionate as a sole source of carbon (23). This enzyme catalyzes the
reaction:
Propionyl-AMP + H 2 0 -> AMP + Propionate
(13)
In summary, depending on the type of organism, there are several
routes for the activation of fatty acids. Once raised to the level of an
acyl CoA derivative, no further activation is necessary. One mole of
ATP is required for the oxidation of a mole of acid regardless of its
81
however, plays no function in either plant or animal tissues, since
acetokinase and phosphotransacetylase are absent; in bacteria these
two enzymes probably play an important role in the formation and
utilization of high-energy phosphate.
In many tissues general as well as specific thiol esterases (deacylases) (18) are found which carry out the irreversible reaction:
RCO-CoA + H 2 0 -> RCOOH + CoA
(11)
The enzymes for the deacylation of succinyl-CoA and acetyl-CoA occur
in heart, liver, and bacterial extracts (19). It is of some interest to
examine the role of these deacylases in tissues. Physiologically, it is
known that in liver tissue acetoacetic acid accumulates and is metabolically inert. But in kidney or in heart tissue acetoacetic acid is
rapidly consumed. It appears that in liver a significant concentration
of an acetoacetyl-CoA deacylase occurs. Moreover ß-keto acid thiokinase (20) which catalyzes the reaction
Acetoacetic acid + CoA + ATP -> Acetoacetyl-CoA + AMP + PP
(12)
is virtually absent in liver but present in kidney and heart (21). Once
acetoacetic acid is formed by deacylation of its CoA derivative in the
liver it becomes metabolically inert. In contrast, in kidney and heart
deacylase activity is low and any circulating acetoacetic acid is rapidly
channeled by the activating enzymes into the metabolic pool (see Section II,C for further discussion).
It is obvious that the control of the concentration of these enzymes
in the cell is of considerable importance in the utilization of acyl CoA
derivatives. For example Lynen (22) observed that octanoyl-CoA thioesterase in mitochondrial preparations acts as a barrier for the synthesis
of long chain fatty acids from acetyl-CoA. Instead of accepting another
acetyl unit for long chain fatty acid synthesis octonoyl-CoA is hydrolyzed to the free acid and thus the thioesterase breaks the chain of
synthesis reactions. Another type of hydrolytic enzyme is propionyl
adenylate hydrolase, which has been found in extracts of an unidentified bacterium isolated from Massachusetts garden soil and grown on
propionate as a sole source of carbon (23). This enzyme catalyzes the
reaction:
Propionyl-AMP + H 2 0 -> AMP + Propionate
(13)
In summary, depending on the type of organism, there are several
routes for the activation of fatty acids. Once raised to the level of an
acyl CoA derivative, no further activation is necessary. One mole of
ATP is required for the oxidation of a mole of acid regardless of its