Pyruvate carboxylase modification

The -amino groups of lysyl residues serve as attachment sites of a number of coenzymes in proteins (e.g. biotin in pyruvate carboxylase, pyridoxal phosphate in phosphorylase, lipoic acid in lipoate acetyl-transferase) and form covalent intermediates in several enzymic reactions (e.g. transaldolase, aldolase, etc.). Discussion of all of these naturally-occuring derivatives of lysine will not be attempted in this treatise, but the investigator using chemical modification of proteins should be aware of their possible presence and effect on the results of his experiments. It should be noted that e-N-phospholysine has been reported in nucleoside diphosphate kinase (Walinder 1968). 

The widespread occurrence of mitochondria in eukaryotic cells indicates that segregation of some of the most important aspects of energy metabolism has been evolutionarily useful. Such segregation has been accompanied by modifications of regulatory interrelationships which depend upon the movement of metabolites into and out of mitochondria and upon the specific modification of regulatory enzymes by specific allosteric modifiers. For example, the activity of pyruvate carboxylase, an enzyme which fulfills an anaplerotic function in a wide variety of cells, depends upon allosteric activation by acetyl CoA. Since the inner mitochondrial membrane is virtually impermeable to coenzyme A and its esters, the activation of pyruvate carboxylase may be looked upon as a compartmentation phenomenon in which this acetyl CoA is separated from the cytosol acetyl CoA pool and must be formed intramitochondrially. In this case movement across the membrane is not involved, since both the activation and the formation of the activator occur within the same compartment. Although a distinct possibility. 

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