Amino acid analysis of plasma metabolites.
As pioneered by Moore and Stein, amino acid analysis is considered the gold standard of protein, peptide, and amino acid testing. The standard amino acid analysis will quantitatively recover most amino acids in a protein, a peptide, or any sample containing proteins, peptides, or amino acids. An amino acid analysis is essential for analyzing free amino acids and other similar biomolecules with primary and secondary amino groups within their structure present in blood serum, plasma, and other body fluids such as urine and cerebrospinal fluid (CSF). CSF is a clear, colorless bodily fluid in the brain and spine. During the last decades, it has become clear that amino acids play a crucial role as metabolites and as regulators of metabolic pathways in mammals, including humans. Since the blood serves as a common medium that links all organs in the body together, plasma amino acid concentrations could be affected by metabolic disturbances in a particular organ system. Therefore, amino acid profiling of blood plasma samples allows for studying levels of amino acid metabolites.
Metabolite profiling usually refers to a set of metabolites and their concentrations detected in a biological sample. Metabolite profiles can be precise for certain classes of chemical compounds, such as lipids or amino acids. Similar to the genome, the full complement of an organism's genes, the metabolome is described as the full complement of metabolites of an organism. The terms "metabolite" and "metabolome" have been established in the scientific literature since 2000. A Pubmed search for "metabolomics" showed that, as of Fall 2013, over 6,100 papers on this subject have already been published thus far. Combining next-generation deep-sequencing technologies with mass spectrometry and other technologies, such as amino acid analysis, will provide more accurate data due to the extensive study of the metabolome in the near future.
Abnormal profiles in amino acid concentrations occur in various diseases such as liver disease, end-stage renal disease, hepatocellular carcinoma, and others. In addition, several plasma peptides are also crucial as hormones in metabolic physiology and diseases. One important peptide class includes the family of cardiac natriuretic peptides. These peptides have emerged as potent metabolic hormones that exhibit a wide range of biological actions and are involved in the control of metabolic homeostasis.
Homeostasis is the ability or tendency of an organism or cell to maintain internal equilibrium. A mammalian body achieves this by adjusting all physiological processes to coordinate responses of its parts to any situation or stimulus that tends to disturb normal conditions or functions to maintain internal stability. The intake of branched-chain amino acids improves the plasma amino acid balance. Therefore, changes in plasma amino acid levels can reflect a patient's metabolic status. For example, patients with the severe hepatic disease have an amino acid imbalance in which low levels of branched-chain amino acids and high levels of aromatic amino acids are observed in their systemic blood when analyzed. Further, increased aromatic amino acid levels in the brain can lead to a decrease in the normal neurotransmitters and an increase in the neurologically inactive phenylethanolamine and octopamine. Peptides with high-branched chain amino acids and low aromatic amino acids are called high-Fischer-ratio oligopeptides.
The formula Fr = (Leu + Val + Ile)/(Tyr + Phe) determines the Fischer ratio between branched-chain amino acids (BCAA) and aromatic amino acids (AAA). This ratio allows the diagnosis of hepatic encephalopathy and its drug treatment efficacy.
Various food proteins contain naturally high Fischer ratio oligopeptides, and amino acid analysis allows for determining their resulting amino acid content.
Reference
Billman GE. Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Front Physiol. 2020 Mar 10;11:200. [PMC]
Kimura T, Noguchi Y, Shikata N, Takahashi M. Plasma amino acid analysis for diagnosis and amino acid-based metabolic networks. Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):49-53. [PubMed]
Physiology, Homeostasis [nih book]
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