Asparagine, transamination reactions

In transamination reactions, amino groups are transferred from one carbon skeleton to another. In reductive animation, amino acids are synthesized by the incorporating of free NH) or the amide nitrogen of glutamine or asparagine into a-keto acids. Ammonium ions are also incorporated into cellular metabolites by the animation of glutamate to form glutamine. 

AMINO ACIDS FORMING OXALOACETATE Both aspartate and asparagine are degraded to form oxaloacetate. Aspartate is converted to oxaloacetate with a single transamination reaction. Asparagine is initially hydrolyzed to yield aspartate and NHJ by asparaginase. 

Aspartate is involved in the control point of pyrimidine biosynthesis (Reaction 1 below), in transamination reactions (Reaction 2 below), interconversions with asparagine (reactions 3 and 4), in the metabolic pathway leading to AMP (reaction 5 below), in the urea cycle (reactions 2 and 8 below), IMP de novo biosynthesis, and is a precursor to homoserine, threonine, isoleucine, and methionine (reaction 7 below). It is also involved in the malate aspartate shuttle. 

The illustrations here and here show the transamination reactions interconverting ot-ketoglutarate, glutamate, and glutamine (see here) and oxaloacetate, aspartate, and asparagine (see here). Notice in each case that one enzyme is primarily involved in the anabolic reactions (making an amino acid) whereas a different enzyme is involved in the catabolic pathway (breaking down an amino acid). 

It was later shown that the apparent asparagine-dependent reaction was due to a small amount of aspartate contamination in samples of commercial asparagine. The aspartate was transaminated to oxaloacetate which then reacted with malate dehydrogenase, an enzyme that is always present in high levels in plant extracts. Repurified asparagine, chratomographically free of aspartate, did not stimulate the rate of NADH oxidation in the presence of 2-oxoglutarate (Miflin and Lea, 1975). 

Asparagine and glutamine are important amide derivatives of the amino acids aspartic acid and glutamic acid. These two amides are also classed as amino acids (Table 4.1) and occur as components of proteins. They also occur as free amides and play an important role in transamination reactions. 

Transamination with Glutamine and Asparagine. Meister and collaborators have described two types of transaminase in which the amino donor is glutamine or asparagine. Transamination from glutamine to any of more than 30 a-keto acids leads to the formation of a-ketoglutaramic acid, which is hydrolyzed by a specific amidase (HI). The reaction... 

S) Amino Acid Amide Transaminases. Mention was made previously (see Amidases) of the observations by Greenstein and co-workers that the addition of pyruvic and other a-keto acids to liver extracts accelerated the formation of ammonia from glutamine and asparagine. This reaction has been shown by Meister and co-workers to involve a transamination reaction different in several respects from those previously discussed. The reaction for glutamine may be formulated as follows ... 

A second type of deamidation reaction for glutamine and asparagine exists. Early work by Greenstein and co-workers demonstrated the existence of an a-keto acid-activated glutaminase and aspart nase in liver 43). It was own later by Meister and associates ( 44, 4 ) that these enzymes catalyze a transamination reaction between the amino acid amides and a-keto acids followed by the hydrolysis of the a-ketoglutaramic or a-ketosuccinamic acids with the release of ammoiua. These reactions will be considered in Section IV, 2. 

Glutamine (and probably asparagine) can be destroyed by two independent routes. The enzyme catalysing direct deamidation to glutamate is activated by phosphate, suggesting a mechanism related to that of glutamine synthetase. The second path involves transamination (equation 30) and subsequent deamidation (equation 31) of a-ketoglutaramic acid. The two reactions are catalysed by separate... 

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