450 



ANIMAL BIOCHEMISTRY 



oxaloacetate 



citrate 



fumarate 



isocitrate 



FIGURE 18-1. The glyoxylatc by-pass mechanism ot tlic tiicarboxylic acid cycle. A 

 more complete presentation of the cycle itself is given in Figure 7-2, page 171. 



ply intermediates for biosynthetic purposes. li a-ketoglutarate, for ex- 

 ample, is withdrawn in making glutamic acid, the original supply of 

 oxaloacetate is not replaced and the cycle should stop. This problem 

 of using the Krebs cycle for both complete oxidation and the supply 

 of intermediates has recently been resolved as follows. 



When any of the compounds of the cycle are withdrawn, isocitrate 

 is diverted through the glyoxalate by-pass shown in Figure 18-1. The 

 two key enzymes yield succinate and glyoxylate first, and the latter 

 then is converted to malate by addition of carbon from acetyl CoA. 

 Oxaloacetate is regenerated by oxidation. The net effect, the forma- 

 tion of a new molecule of a four-carbon acid by utilizing two mole- 

 cules of acetyl CoA, becomes possible because the steps eliminating 

 carbon dioxide are by-passed. This new molecule may be used in 

 other reaction systems, or it may be enlarged by reaction with still an- 

 other acetyl CoA to form citrate, which may proceed in turn to a-keto- 

 glutarate by decarboxylation. In this way the tricarboxylic acid cycle 

 continuously supplies a-ketoglutarate for glutamic acid, fumarate and 

 oxaloacetate for aspartic acid. 



