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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| L-Leucine | |
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| Chemical Name | (2S)-2-amino-4-methyl-pentanoic acid |
| Chemical Formula | C6H13NO2 |
| CAS Number | 61-90-5 |
| Chemical Information | HMDB00687 |
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| Nutritional Taxonomy |
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| Metabolic Pathways | Not Available |
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| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available |
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| Other (Monogenic Disorders) |
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| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available |
| Physiological Processes | Not Available |
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Contents |
Introduction
guidelines
Branched chain amino acids (BCAA) are essential amino acids whose carbon structure is marked by a branch point. "BCAA" denotes valine, isoleucine and leucine which are branched chain essential amino acids. These three amino acids are critical to human life and are particularly involved in stress, energy and muscle metabolism. BCAA supplementation as therapy, both oral and intravenous, in human health and disease holds great promise. Despite their structural similarities, the branched amino acids have different metabolic routes, with valine going solely to carbohydrates, leucine solely to fats and isoleucine to both. The different metabolism accounts for different requirements for these essential amino acids in humans: 12 mg/kg, 14 mg/kg and 16 mg/kg of valine, leucine and isoleucine respectively. Furthermore, these amino acids have different deficiency symptoms. Valine deficiency is marked by neurological defects in the brain, while isoleucine deficiency is marked by muscle tremors. Many types of inborn errors of BCAA metabolism exist, and are marked by various abnormalities. The most common form is the maple syrup urine disease, marked by a characteristic urinary odor. Other abnormalities are associated with a wide range of symptoms, such as mental retardation, ataxia, hypoglycemia, spinal muscle atrophy, rash, vomiting and excessive muscle movement. Most forms of BCAA metabolism errors are corrected by dietary restriction of BCAA and at least one form is correctable by supplementation with 10 mg of biotin daily. BCAA are decreased in patients with liver disease, such as hepatitis, hepatic coma, cirrhosis, extrahepatic biliary atresia or portacaval shunt; aromatic amino acids (AAA)-tyrosine, tryptophan and phenylalanine, as well as methionine-are increased in these conditions. Valine in particular, has been established as a useful supplemental therapy to the ailing liver. All the BCAA probably compete with AAA for absorption into the brain. Supplemental BCAA with vitamin B6 and zinc help normalize the BCAA:AAA ratio. (http://www.dcnutrition.com)
The combination of these three essential amino acids make up approximately 1/3 of skeletal muscle in the human body, and play an important role in protein synthesis. BCAA’s are currently used clinically to aid in the recovery of burn victims, as well as for supplementation for strength athletes. The BCAAs affect this metabolic pathway in three different manners. The first manner through which the metabolic pathway is affected is the increased production of insulin. It has been demonstrated that BCAA supplementation in accordance with carbohydrate intake following resistance exercise increases insulin output by 221%, which is much greater than the 66% supplementation without leucine. Leucine is the most readily oxidized BCAA and therefore the most effective at causing insulin secretion from the pancreas, and stimulating the metabolic pathway. This is important because insulin is the initiating factor that begins the signalling cascade. The second effect is a phosphorylation cascade beginning with the activation of the Ras Rhed and ending with rpS6. The importance of rpS6 is that it induces mRNA translation. This translation leads to the production of proteins to build muscle. Furthermore, the pathway induces the action of eIF4G. This initiation factor causes the binding of mRNA within the ribosome thus providing the initial products needed for translation. This leads down to the final product via protein binding and phosphorylation, resulting in eIF4E which induces mRNA translation which in turn leads to chain elongation, and termination, resulting in net protein growth (wikipedia).
Biological Function
guidelines
BCAA are used specifically for peptide and protein synthesis and do not serve as precursors to neurotransmitters or bile acids like several other amino acids. The BCAAs make up 35% of muscle proteins. During strenuous muscle activity, they serve as a source of energy regulation, giving rise to alanine and glutamine for conversion by the liver and kidney to glucose. The carbon skeletons of Ile and val are catabloized to succinate, a key intermediate in the citric acid cycle. Stress induces a decrease of muscle protein synthesis. Vitamin B6 is critical for amino acid metabolism. The cofactor form, pyridoxal-5-phosphate, is required for all transamination reactions. Plasma BCAA elevations may result from inadequate vitamin B6.
An active insulin response is required for clearing amino acids from plasma. BCAA levels are increased in diabetes type II.
Skeletal muscle is the major destination for plasma BCAAs. their incorporation is dependent on insulin-growth factor (IGF-1). Both insulin and IGF-1 are responsible for anabolic effects in skeletal muscle. IGF-1 stimulates protein synthesis, while insulin inhibits protein breakdown by stimulating amino acid uptake. The net effect is thay both falling IGF-1 levels and insensitivity to insulin lead to higher plasma BCAA. Conversely, raising BCAA levels in plasma increases the rate of lean body mass increase in response to excersize. Muscle protein synthesis is increased when plasma amino acid levels are raised.
From: laboratory evaluations in molcular medicine, nutrients, toxicants and cell regulators, 2005, J. Alexander Bralley and Richard S. Lord, ISBN 0-9673949-3-7
Catabolism
Diseases / Conditions Related to Nutrition
- Acute seizures
- Neonatal Maple syrup urine Disease (MSUD)
- Neonatal phenylketonuria
- Nondiabetic patients with Chronic Heart Failure
- Refractory localization-related epilepsy (RLE)
- leukemia
- leukemia with CNS disease
Other (Monogenic) Disorders
- Hypoglycemia, leucine-induced OMIM: 240800
Nutritional Information
Drivers for biological variation
guidelines
Stimulation of glucose metabolism is known to inhibit proteolysis by action of insulin. This leads to decreased concentrations of plasma amino acids measured by isoleucine/leucine concentratuons at 30, 60, 90 and 120 minutes after a glucose challenge (Shaham et al Pubmed).