II GLUCOSE, FATTY ACIDS CATABOLISM 9 



conditions of ketogenesis in the liver, COj may also be Ibrmed by the decarboxyla- 

 tion of acetoacetate : 



4) Acetoacetate — » CO2 + acetone 



The oxidative decarboxylation of 6-phosphogluconate represents a fifth reaction 

 in which CO, is generated : 



5) 6-Phosphogluconate — > ribulose phosphate + CO2 



These then are the principal chemical reactions which account for the formation 

 of CO2 in animal tissues. It may be noted however that some COj may be formed 

 as a result of the decarboxylation of a number of amino acids and metabolites of 

 amino acids. Pyridoxal phosphate is a coenzyme for these amino acid decar- 

 boxylases. Some of the amino acid decarboxylation reactions occur primarily 

 in bacteria while those which take place in mammalian tissues are of importance 

 in the terminal steps of hormone synthesis. 



7. Oxidative steps 



As shown in Fig. i , there are two oxidative steps in the direct oxidative pathway 

 of glucose metabolism. Likewise, the conversion of glyceraldehyde phosphate to 

 I, 3-diphosphoglyceric acid, a-glycerophosphate to dihydroxyacetone phosphate, 

 lactate to pyruvate, acetyl lipothiamide to acetyl-CoA and lipothiamide, all 

 involve oxidation-reduction reactions. There are four oxidation steps in the tri- 

 carboxylic acid cycle and two for each turn of the fatty acid spiral. 



In all but two of the examples cited above, pyridine nucleotides participate as 

 cofactors. The two exceptions are the acyl dehydrogenase of the fatty acid spiral 

 and the succinic dehydrogenase of the tricarboxylic acid cycle. It should first be 

 emphasized that oxidation-reduction reactions involving pyridine nucleotides are 

 extremely common. In Table i, there are collected over 70 pyridine nucleotide 

 linked oxidation-reduction reactions. Although in most of these, the nicotinic acid 

 derivative is diphosphopyridine nucleotide (DPN^), many triphosphopyridine 

 nucleotide (TPN"^) reactions are also known. These include the oxidation of 

 isocitric acid, glucose-6-phosphate, and 6-phosphogluconate. 



The reactions of Table i are classified as suggested by Racker (1955). Pyridine nucleo- 

 tides are involved in the oxidation of alcohols to aldehydes, aldehydes to acids, hydroxy 

 acids to keto acids, hemiacetals to aldonic acid lactones, and in the oxidation of cyclic 

 compounds, mercaptols, and other compounds. Many of these oxidation reactions are 

 essential steps in biosynthetic sequences. For example the oxidation of dihydroorotic acid 

 to orotic acid is one of the steps of pyrimidine synthesis, while the reduction of aspartic 

 semialdehyde to homoserine is a step in the synthesis of the amino acids, methionine and 

 threonine. The pyridine nucleotide dehydrogenases are so numerous and the substrates 

 so varied that pyridine nucleotide enzymes have rightfully been called the "work horses" 

 of biological oxidations. Pyridine nucleotide dehydrogenases also function in amino acid 

 oxidation, sterol synthesis, and in the maintenance of the redox-potential of the cell. 



The oxidation process involves the transfer of two electrons and a hydrogen 

 atom to the nicotinamide portion of the coenzyme while the second hydrogen 

 atom is released as an ion in solution (Fig. 4, p. 14). 



Literature j>. 124 text continued on p. 14 



