Valine: Definition, Synthesis, Absorption, Transport, and Distribution

Valine (Val) is the third branched-chain amino acid – English : Branched Chain Amino Acids (BCAAs). Like leucine and isoleucine, valine has a branched chain arrangement in its structure. Because of this specific molecular structure, neither the animal nor the human organism can build up valine, which is why this amino acid is called essential (necessary for life). Finally, valine must be ingested in sufficient amounts with dietary protein to maintain a nitrogen balance and allow normal growth.Valine is one of a total of 21 proteinogenic amino acids used to build proteins. All major proteins of the body contain valine in concentrations of 5-8%. Depending on the structure of their side chains, proteinogenic amino acids are divided into different groups. Valine, like isoleucine, leucine, alanine and glycine, is an amino acid with an aliphatic side chain. Aliphatic amino acids carry only one carbon side chain and are nonpolar. Valine is one of the neutral amino acids, which is why it can behave both acidically – releasing protons – and alkaline – receiving protons. In 1901, Herman Emil Fischer, the founder of modern biochemistry, isolated the essential amino acid valine from casein for the first time. Casein is a coarse coagulating protein of milk and therefore the main component of cheese and curd. Structurally, valine is derived from isovaleric acid by substitution of a hydrogen atom with an amino group (NH2), a monocarboxylic acid hemiterpene also known as 3-methylbutyric acid.

Protein digestion and intestinal absorption

Partial hydrolysis of dietary proteins begins in the stomach. Major substances for protein digestion are secreted from various cells in the gastric mucosa. Major and minor cells produce pepsinogen, the precursor of the protein-cleaving enzyme pepsin. Stomach cells produce gastric acid, which promotes the conversion of pepsinogen to pepsin. In addition, gastric acid lowers pH, which increases pepsin activity. Pepsin breaks down valine-rich protein into low-molecular-weight cleavage products, such as poly- and oligopeptides. Good natural sources of valine include casein, whey, egg, meat, oat, whole rice and hazelnut proteins. The soluble poly- and oligopeptides subsequently enter the small intestine, the site of major proteolysis (protein digestion). Proteases (protein-cleaving enzymes) are produced in the pancreas. The proteases are initially synthesized and secreted as zymogens – inactive precursors. It is only in the small intestine that they are activated by enteropeptidases – enzymes formed from the mucosa cells – calcium and the digestive enzyme trypsin. The most important proteases include endopeptidases and exopeptidases. Endopeptidases cleave proteins and polypeptides inside molecules, increasing the terminal attackability of proteins. Exopeptidases attack the peptide bonds of the chain end and can specifically cleave certain amino acids from the carboxyl or amino end of protein molecules. They are referred to as carboxy- or aminopeptidases accordingly. Endopeptidases and exopeptidases complement each other in the cleavage of proteins and polypeptides due to their different substrate specificity. Specific aliphatic amino acids, including valine, are released by the endopeptidase elastase. Valine is subsequently located at the end of the protein and is thus accessible for cleavage by carboxypeptidase A. This exopeptidase cleaves aliphatic as well as aromatic amino acids from oligopeptides. Valine is predominantly absorbed actively and electrogenically in sodium cotransport into the enterocytes (mucosa cells) of the small intestine. About 30 to 50% of the absorbed valine is already degraded and metabolized in the enterocytes. Transport of valine and its metabolites from the cells via the portal system to the liver occurs along the concentration gradient via various transport systems. Intestinal absorption of amino acids is nearly complete at almost 100 percent. Essential amino acids, such as valine, isoleucine, leucine, and methionine, are absorbed much more rapidly than nonessential amino acids.The breakdown of dietary and endogenous proteins into smaller cleavage products is not only important for peptide and amino acid uptake into enterocytes, but also serves to resolve the foreign nature of the protein molecule and to preclude immunological reactions.

Protein degradation

Valine and other amino acids can be metabolized and degraded in all tissues of the organism, releasing NH3 in principle in all cells and organs. Ammonia enables the synthesis of non-essential amino acids, purines, porphyrins, plasma proteins and proteins of the defense against infections. Since NH3 in free form is neurotoxic even in very small amounts, it must be fixed and excreted. Ammonia can cause serious cell damage by inhibiting energy metabolism and pH shifts. Fixation occurs through the glutamate dehydrogenase reaction. In this process, ammonia released in extrahepatic tissues is transferred to alpha-ketoglutarate, producing glutamate. The transfer of a second amino group to glutamate results in the formation of glutamine. The process of glutamine synthesis serves as a preliminary ammonia detoxification. Glutamine, which is mainly formed in the brain, transports the bound and thus harmless NH3 to the liver. Other forms of transport of ammonia to the liver are aspartic acid and alanine. The latter amino acid is formed by binding of ammonia to pyruvate in the muscles. In the liver, ammonia is released from glutamine, glutamate, alanine and aspartate. NH3 is now introduced into the hepatocytes – liver cells – for final detoxification with the help of carbamyl-phosphate synthetase in urea biosynthesis. Two ammonia molecules form a molecule of urea, which is non-toxic and excreted through the kidneys in the urine. Via the formation of urea, 1-2 moles of ammonia can be eliminated daily. The extent of urea synthesis is subject to the influence of diet, especially protein intake in terms of quantity and biological quality. In an average diet, the amount of urea in daily urine is in the range of about 30 grams. Individuals with impaired renal function are unable to excrete excess urea through the kidney. Affected individuals should follow a low-protein diet to avoid increased production and accumulation of urea in the kidney due to amino acid breakdown.