Leucine – Leu – is one of a total of 21 proteinogenic amino acids used to build proteins.Depending on the structure of their side chains, proteinogenic amino acids are divided into different groups. Leucine, like isoleucine, valine, alanine and glycine, is an amino acid with an aliphatic side chain. Aliphatic amino acids carry only one carbon side chain and are nonpolar.Leucine, isoleucine and valine are called branched-chain amino acids because of their specific molecular structure: Branched Chain Amino Acids (BCAAs).The BCAAs are among the neutral amino acids, which is why they can behave both acidic – release of protons – and basic – uptake of protons.Leucine cannot be synthesized by the human body itself and is therefore essential. As an amino acid essential for life, leucine must be ingested in sufficient amounts with dietary protein to maintain a balanced nitrogen diet and allow normal growth.
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 leucine-rich protein into low-molecular-weight cleavage products, such as poly- and oligopeptides. Good natural sources of leucine include whey, egg, oat, corn, millet, and hazelnut protein, as well as casein.The soluble poly- and oligopeptides subsequently enter the small intestine, the site of the main proteolysis-protein digestion. In the pancreas, proteases – protein-cleaving enzymes – are formed. 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 the 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 due to different substrate specificity in the cleavage of proteins and polypeptides.The endopeptidase elastase specifically releases aliphatic amino acids, including leucine. Leucine is subsequently located at the end of the protein and is thus accessible for cleavage by carboxypeptidase A. This exopeptidase cleaves both aliphatic and aromatic amino acids from oligopeptides.Leucine 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 leucine is already degraded and metabolized in the enterocytes. Transport of leucine and its metabolites from the cells via the portal system to the liver occurs through various transport systems along the concentration gradient.Intestinal absorption of amino acids is almost complete at nearly 100 percent. Essential amino acids, such as leucine, isoleucine, valine, and methionine, are absorbed much more rapidly than nonessential amino acids. The breakdown of dietary proteins 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
Leucine 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 lead to 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, forming 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 is excreted through the kidneys in the urine.1-2 moles of ammonia can be eliminated daily via the formation of urea. 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.
