BioFiles Volume 4, Number 8 — Metabolomics

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Table of Contents




The metabolic pathways around the 20 common α-amino acids are unique for each amino acid, but also central to all living organisms. Plants and microorganisms can produce their own amino acids, whereas mammals/humans can do this only partially. They need to digest proteins in order to obtain several of their amino acids. Selective inhibition of amino acid biosynthesis is therefore of high interest in the agrochemical and pharmaceutical industry as a strategy to destroy undesired plants or pathogens without affecting mammals/humans.

The metabolic breakdown of the common α-amino acids starts with the removal of the α-amino group as either ammonia or aspartate, which can directly be excreted to the surroundings by fish and other aquatic animals. Terrestrial organisms however must convert the ammonia into a non-toxic compound like urea (mammals) or uric acid (birds and reptiles). The remaining amino acid carbon skeleton, capable of entering the citric acid cycle.

The tasks within the metabolic pathways to synthesize the common 20 amino acids as building blocks for proteins are distributed differently in the biosphere. Humans are able to synthesize 11 out of the 20 amino acids, while the other 9 amino acids are only synthesized in plants or microorganisms and must therefore be taken up by humans and other higher organisms through nutrition.

Genetics, birth, development and adaptation, health and disease, stage of life and environment can bring in major shifts to the amino acid, protein and energy metabolism. Amino acid metabolism is therefore influenced by a variety of factors, which can be investigated directly at the amino acid level or at the related metabolite level in the corresponding amino acid pathway.

The introduction of non-radioactive and stable isotope tracer methods has enabled safe investigations of protein and amino acid metabolism from microorganisms, plants, animals or humans. Nutritional and pathological conditions can influence protein deficiencies leading to amino acid limitations or on the other hand can lead to a surplus of amino acids in metabolic diseases. As a correct level of amino acids is vital, the biosynthesis of amino acids is regulated by a variety of mechanisms at the DNA, RNA or protein level. In the biosynthesis of amino acids, induction or repression of enzymes are not the most important regulation mechanisms. Different amino acid riboswitches have been discovered which act on the RNA level by selectively sensing the corresponding amino acid. The most important regulatory mechanism is feedback regulation at the level of enzyme action and enzyme synthesis.

The diversity of natural amino acid metabolic pathways and their connections show the importance of a balanced and robust supply of these molecules for a healthy state of biological cells. Therefore, it is not surprising that L-amino acids are among the most important industrial central metabolites, manufactured at 100 to 1,500,000 ton scale for the cosmetic, food, feed and nutraceutical industries. The experience in the optimization of amino acid production levels in industry has clearly shown that detailed quantitative knowledge of the metabolism is required in order to design superior production strains.

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