Biochemistry of Amino Acids - A. Meister 1961

General Biochemistry and Physiology of Amino Acid Metabolism
Synthesis of Peptide Bonds
Synthesis of Other Compounds Containing -CONH- Bonds

A number of studies have focused on the Biosynthesis of certain other low-molecular-weight compounds containing —CONH— bonds (such as carnosine, asparagine, penicillin, and pantothenic acid), but overall, less is known about these enzyme systems than about those involved in the Synthesis of Glutathione and glutamine. It was found that the enzyme system activating glutamine synthesis does not catalyze The formation of asparagine from L-aspartic acid, ammonia, and adenosine triphosphate. The formation of asparagine has been described via Transamination reactions—specifically, by transferring an amino group to the ß-amide of oxaloacetic acid (β-amide of ketosuccinic acid) ([290], p. 223)—as well as through The transfer of an amide group from glutamine to aspartic acid [573]. The possibility of asparagine formation from aspartic acid, ammonia, and adenosine triphosphate via an enzyme system distinct from the one synthesizing glutamine was also discussed [574]. It was found that wheat germ preparations catalyze the formation of ß-aspartylhydroxamic acid from L-aspartic acid and hydroxylamine in the presence of magnesium ions and adenosine triphosphate. It remains unclear whether the system involved in the formation of ß-aspartylhydroxamic acid also catalyzes asparagine synthesis. In Yeast, an analogous reaction catalyzes the formation of ß-aspartyl phosphate; the latter apparently does not serve as an asparagine precursor, yet it has been established as an intermediate in the formation of homoserine from aspartic acid (p. 333). Unlike the glutamine-synthesizing system, the wheat germ enzyme system that synthesizes ß-aspartylhydroxamic acid requires high concentrations of aspartic acid and hydroxylamine. Evidence indicates that the wheat germ system catalyzes the incorporation of C¹⁴-aspartic acid into asparagine in the presence of adenosine triphosphate, ammonia, and magnesium ions; however, it remains uncertain whether a true net synthesis of asparagine actually occurs. A detailed examination of The Mechanism of asparagine synthesis should be deferred until further data become available.

The formation of carnosine from ß-Alanine and Histidine was demonstrated in experiments using Liver slices. To detect carnosine synthesis, a microbiological assay for histidine was employed, with determinations performed both before and after acid Hydrolysis [575]. Data obtained using labeled ß-alanine confirmed the formation of carnosine from ß-alanine and histidine [576].

Considerable attention has been devoted to studying the synthesis of pantothenic acid from ß-alanine and pantoic acid. The reaction apparently does not require coenzyme A; however, it requires the presence of adenosine triphosphate, magnesium (or manganese) ions, and potassium (or ammonium) ions. For a Structure/133.html">Discussion of this reaction, see p. 311.

¹ The existence of such a transamidation reaction has not been confirmed [Xu Tii-sen, Biochemistry, 24, 528 (1959)]. — Ed. note.

The synthesis of penicillin by Penicillium strains has been studied using labeled Amino Acids. Upon adding labeled DL-valine to the Fermentation medium, Stevens et al. [577] found that the carboxyl group of penicillin could be derived from valine; when valine is labeled in the methyl groups, it is incorporated into the penicillamine moiety of the antibiotic molecule [578]. L-Valine appears to be incorporated more rapidly than D-valine [709]. A wide variety of acids can serve as precursors for the acyl group [579], while L-cystine is apparently the source of the β-lactam ring [578–581, 709, 710]. L-Cystine is a more effective precursor for penicillin than D-cystine [578].

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Elucidating the mechanism of penicillin formation from these precursors remains a task for future research (see [710]).