Amino Acid Biosynthesis

Amino acid biosynthesis is the anabolic side of amino acid metabolism: the construction of amino acids from simpler precursors drawn largely from central metabolic pathways. In humans, this capacity is partial, which is why some amino acids are nonessential and made internally while others are essential and must come from the diet.

Definition

Amino acid biosynthesis is the synthesis of amino acids from carbon skeletons supplied by central metabolism together with an amino group donated by other nitrogen carriers, producing in humans the nonessential amino acids while the essential amino acids must be obtained from the diet.

Scope

This entry covers how the nonessential amino acids are synthesized from glycolytic and citric-acid-cycle intermediates, the role of nitrogen donors such as glutamate and glutamine, and the distinction between essential and nonessential amino acids in humans. The reading and assembly of amino acids into proteins is covered in the translation entry, and their breakdown in the catabolism entry.

Core questions

• Which carbon skeletons serve as precursors for the nonessential amino acids?
• How is nitrogen supplied during biosynthesis?
• Why can humans make some amino acids but not others?

Key concepts

• Essential versus nonessential amino acids
• Precursors from glycolysis and the citric acid cycle
• Glutamate and glutamine as amino-group donors
• Transamination in the synthetic direction
• Amidation reactions (glutamine and asparagine synthesis)
• Conditionally essential amino acids

Mechanisms

The nonessential amino acids are built from a handful of central metabolites. Pyruvate, oxaloacetate, and alpha-ketoglutarate are converted by transamination, run in the synthetic direction, into alanine, aspartate, and glutamate respectively, with glutamate frequently serving as the amino-group donor. The 3-phosphoglycerate of glycolysis is the precursor for serine, from which glycine and cysteine can derive. Amidation reactions add a second nitrogen to make glutamine from glutamate and asparagine from aspartate, the latter catalyzed by asparagine synthetase. By contrast, the carbon skeletons and biosynthetic routes of the essential amino acids are not present in humans, so these must be supplied by the diet; the boundary can shift under stress or in certain conditions, giving rise to conditionally essential amino acids.

Clinical relevance

The dependence of some tissues on amino acid supply, including the requirement for dietary essential amino acids, underlies nutrition science and helps explain why certain tumors that cannot make particular amino acids are sensitive to their depletion. This entry describes the biochemistry and is not a basis for individual dietary or treatment decisions.

Evidence & guidelines

The biosynthetic pathways are established biochemistry consolidated in standard texts and reviews; this is a reference topic rather than a clinical guideline domain.

History

The biosynthetic routes to individual amino acids were mapped through mid-twentieth-century enzymology and microbial genetics, including the use of biosynthetic mutants to order the steps of pathways, work that established which carbon skeletons and nitrogen donors feed each amino acid.

Key figures

• David Greenberg
• Bernard Davis

Seminal works

• wu-2009
• lomelino-2017

Frequently asked questions

What makes an amino acid essential?

An amino acid is essential when the body lacks the pathways to synthesize it in adequate amounts, so it must be obtained from the diet; nonessential amino acids can be made internally from other metabolites.

Where do the carbon skeletons for nonessential amino acids come from?

They come largely from intermediates of glycolysis and the citric acid cycle, such as pyruvate, oxaloacetate, alpha-ketoglutarate, and 3-phosphoglycerate, which are converted to amino acids by adding an amino group.