Amino Acid Hydroxamates Research Articles

Activation of amino-acids by soluble enzymes from pancreas and other tissues.

LAST year, Hoagland1 reported that he had obtained from rat liver a soluble enzyme preparation which catalysed the formation of amino-acid hydroxamates when incubated with a mixture of twelve amino-acids in the presence of adenosine triphosphate and hydroxylamine. He suggested that this type of carboxyl group activation might be a first step in protein synthesis. In a later paper with Keller and Zamecnik2 he reported partial purification of activating enzyme from liver.

An amino acid dependent exchange between 32P labeled inorganic pyrophosphate and ATP in microbial extracts

An enzyme system which catalyzes a rapid, amino acid dependent exchange between inorganic pyrophosphate and ATP has been found to be ubiquitously distributed in microorganisms. The reaction is dependent upon the presence of amino acids. Only leucine, isoleucine, valine, tryptophan, tyrosine, histidine, phenylalanine, and methionine are active in the system. The reaction is specific for the l-form of the amino acids and for ATP; all other nucleotide triphosphates tested being inactive. The reaction mechanism appears to involve the intermediate formation of aminoacyl-AMP, which appears to have a low order of dissociation from the enzyme surface. In the presence of excess hydroxylamine the intermediate is trapped with the corresponding formation of amino acid hydroxamate, indicating carboxyl activation. The rate of the exchange reaction is 20 to 50 times faster than the reaction with hydroxylamine. Leucyl-AMP has been chemically synthesized and shown to participate as an intermediate in the exchange reaction. The possible significance of this reaction to protein synthesis is discussed.