Singapore Drugs Database

Indication

Supplemental glycine may have antispastic activity. Very early findings suggest it may also have antipsychotic activity as well as antioxidant and anti-inflammatory activities.

Mechanism of Action

In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia.
Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.

Pharmacokinetics

Absorption

Absorbed from the small intestine via an active transport mechanism.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

ORL-RAT LD₅₀ 7930 mg/kg, SCU-RAT LD₅₀ 5200 mg/kg, IVN-RAT LD₅₀ 2600 mg/kg, ORL-MUS LD₅₀ 4920 mg/kg; Doses of 1 gram daily are very well tolerated. Mild gastrointestinal symptoms are infrequently noted. In one study doses of 90 grams daily were also well tole.

Active Ingredient/Synonyms

Aminoacetic acid | Aminoessigsäure | Aminoethanoic acid | Gly | Glycin | Glycocoll | Glykokoll | Glyzin | Leimzucker | Glycine |

Indication

Used for nutritional supplementation, also for treating dietary shortage or imbalance.

Mechanism of Action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacokinetics

Absorption

Absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism.

Distribution

Metabolism

Some metabolism of L-arginine takes place in the enterocytes. L-arginine not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized.

Elimination

Toxicity

Oral supplementation with L-arginine at doses up to 15 grams daily are generally well tolerated. The most common adverse reactions of higher doses from 15 to 30 grams daily are nausea, abdominal cramps and diarrhea. Some may experience these symptoms at lower doses.

Active Ingredient/Synonyms

(2S)-2-amino-5-(carbamimidamido)pentanoic acid | (2S)-2-amino-5-guanidinopentanoic acid | (S)-2-amino-5-guanidinopentanoic acid | (S)-2-Amino-5-guanidinovaleric acid | Arg | Arginine | L-(+)-Arginine | L-Arg | L-Arginin | R | L-Arginine |

Indication

For the treatment of Hypertension

Mechanism of Action

Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.

Pharmacokinetics

Absorption

Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.

Distribution

Metabolism

Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme.

Elimination

Toxicity

LD₅₀=740mg/kg (orally in mice)

Active Ingredient/Synonyms

(+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate ester | (2S-cis)-3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one | (2S,3S)-5-(2-(dimethylamino)ethyl)-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate | Acetic acid (2S,3S)-5-(2-dimethylamino-ethyl)-2-(4-methoxy-phenyl)-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]thiazepin-3-yl ester | D-cis-diltiazem | Diltiazem | Diltiazemum | Diltiazem |

Indication

Used for protein synthesis.

Mechanism of Action

L-Alanine is a non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. BCAAs are used as a source of energy for muscle cells. During prolonged exercise, BCAAs are released from skeletal muscles and their carbon backbones are used as fuel, while their nitrogen portion is used to form another amino acid, Alanine. Alanine is then converted to Glucose by the liver. This form of energy production is called the Alanine-Glucose cycle, and it plays a major role in maintaining the body's blood sugar balance.

Active Ingredient/Synonyms

(2S)-2-aminopropanoic acid | (S)-2-aminopropanoic acid | (S)-alanine | Alanine | L-2-Aminopropionic acid | L-Alanin | L-alpha-Alanine | L-α-alanine | L-Alanine |

Indication

The actions of supplemental L-histidine are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. L-histidine may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.

Mechanism of Action

Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints.
L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis.
This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

Pharmacokinetics

Absorption

Absorbed from the small intestine via an active transport mechanism requiring the presence of sodium.

Distribution

Metabolism

Elimination

Toxicity

ORL-RAT LD₅₀ > 15000 mg/kg, IPR-RAT LD₅₀ > 8000 mg/kg, ORL-MUS LD₅₀ > 15000 mg/kg, IVN-MUS LD₅₀ > 2000 mg/kg; Mild gastrointestinal side effects.

Active Ingredient/Synonyms

(S)-4-(2-Amino-2-carboxyethyl)imidazole | (S)-a-Amino-1H-imidazole-4-propanoic acid | (S)-alpha-amino-1H-Imidazole-4-propanoic acid | (S)-alpha-Amino-1H-imidazole-4-propionic acid | (S)-α-amino-1H-Imidazole-4-propanoic acid | HIS | Histidina | L-(−)-histidine | L-Histidin | L-Histidine | Histidine |

Indication

The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.

Mechanism of Action

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium-dependent active-transport process

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs

Active Ingredient/Synonyms

(2S,3S)-2-Amino-3-methylpentanoic acid | 2-Amino-3-methylvaleric acid | alpha-amino-beta-methylvaleric acid | I | Ile | Isoleucine | L-Isoleucine | α-amino-β-methylvaleric acid | L-Isoleucine |

Indication

Indicated to assist in the prevention of the breakdown of muscle proteins that sometimes occur after trauma or severe stress.

Mechanism of Action

This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Active Ingredient/Synonyms

(2S)-2-Amino-4-methylpentanoic acid | (2S)-alpha-2-Amino-4-methylvaleric acid | (2S)-alpha-Leucine | (S)-(+)-Leucine | (S)-Leucine | 2-Amino-4-methylvaleric acid | L | L-Leucin | L-Leuzin | Leu | Leucine | L-Leucine |

Indication

Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

Mechanism of Action

The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.

Pharmacokinetics

Absorption

Absorbed from the lumen of the small intestine into the enterocytes by an active transport process.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Doses of L-methionine of up to 250 mg daily are generally well tolerated. Higher doses may cause nausea, vomiting and headache. Healthy adults taking 8 grams of L-methionine daily for four days were found to have reduced serum folate levels and leucocytosis. Healthy adults taking 13.9 grams of L-methionine daily for five days were found to have changes in serum pH and potassium and increased urinary calcium excretion. Schizophrenic patients given 10 to 20 grams of L-methionine daily for two weeks developed functional psychoses. Single doses of 8 grams precipitated encephalopathy in patients with cirrhosis.

Active Ingredient/Synonyms

(2S)-2-amino-4-(methylsulfanyl)butanoic acid | (S)-2-amino-4-(methylthio)butanoic acid | (S)-2-amino-4-(methylthio)butyric acid | (S)-methionine | L-(−)-methionine | L-a-Amino-g-methylthiobutyric acid | L-Methionin | L-Methionine | L-α-amino-γ-methylmercaptobutyric acid | M | Met | Methionine |

Indication

L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.

Mechanism of Action

The mechanism of L-phenylalanine's putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium dependent active transport process.

Distribution

Metabolism

Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.

Elimination

Toxicity

L-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.

Active Ingredient/Synonyms

(S)-2-Amino-3-phenylpropionic acid | (S)-alpha-Amino-beta-phenylpropionic acid | 3-phenyl-L-alanine | beta-Phenyl-L-alanine | F | Phe | Phenylalanine | β-phenyl-L-alanine | L-Phenylalanine |

Indication

L-Proline is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.

Mechanism of Action

Glycogenic, by L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde. It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.

Active Ingredient/Synonyms

(-)-2-Pyrrolidinecarboxylic acid | (−)-(S)-proline | (−)-2-pyrrolidinecarboxylic acid | (−)-proline | (2S)-pyrrolidine-2-carboxylic acid | (S)-2-Carboxypyrrolidine | (S)-2-Pyrrolidinecarboxylic acid | (S)-pyrrolidine-2-carboxylic acid | 2-Pyrrolidinecarboxylic acid | L-(−)-proline | L-alpha-pyrrolidinecarboxylic acid | L-Prolin | L-pyrrolidine-2-carboxylic acid | L-α-pyrrolidinecarboxylic acid | P | Prolina | Proline | Prolinum | L-Proline |

Indication

Used as a natural moisturizing agent in some cosmetics and skin care products.

Mechanism of Action

L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.

Active Ingredient/Synonyms

(S)-2-Amino-3-hydroxypropanoic acid | (S)-Serine | alpha-Amino-beta-hydroxypropionic acid | beta-Hydroxyalanine | L-Serine | Ser | Serina | Serinum | Serine |

Indication

L-Threonine makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

Mechanism of Action

L-Threonine is a precursor to the amino acids glycine and serine. It acts as a lipotropic in controlling fat build-up in the liver. May help combat mental illness and may be very useful in indigestion and intestinal malfunctions. Also, threonine prevents excessive liver fat. Nutrients are more readily absorbed when threonine is present.

Active Ingredient/Synonyms

(2S,3R)-(-)-Threonine | (2S)-threonine | 2-Amino-3-hydroxybutyric acid | L-(-)-Threonine | L-2-Amino-3-hydroxybutyric acid | L-alpha-amino-beta-hydroxybutyric acid | L-Threonin | L-α-amino-β-hydroxybutyric acid | Thr | Threonine | L-Threonine |

Indication

Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

Mechanism of Action

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD⁺ and NADP⁺.

Toxicity

Oral rat LD₅₀: > 16 gm/kg. Investigated as a tumorigen, mutagen, reproductive effector. Symptoms of overdose include agitation, confusion, diarrhea, fever, overactive reflexes, poor coordination, restlessness, shivering, sweating, talking or acting with excitement you cannot control, trembling or shaking, twitching, and vomiting.

Active Ingredient/Synonyms

(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid | (S)-alpha-Amino-beta-(3-indolyl)-propionic acid | (S)-Tryptophan | (S)-α-amino-1H-indole-3-propanoic acid | L-(-)-Tryptophan | L-(−)-tryptophan | L-β-3-indolylalanine | Trp | Tryptophan | W | L-Tryptophan |

Indication

Promotes mental vigor, muscle coordination, and calm emotions. May also be of use in a minority of patients with hepatic encephalopathy and in some with phenylketonuria.

Mechanism of Action

(Applies to Valine, Leucine and Isoleucine)
This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates.
The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic.
There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS.

Pharmacokinetics

Absorption

Absorbed from the small intestine by a sodium-dependent active-transport process.

Distribution

Metabolism

Hepatic

Elimination

Toxicity

Symptoms of hypoglycemia, increased mortality in ALS patients taking large doses of BCAAs.

Active Ingredient/Synonyms

(2S)-2-Amino-3-methylbutanoic acid | (S)-Valine | 2-Amino-3-methylbutyric acid | L-(+)-alpha-Aminoisovaleric acid | L-alpha-Amino-beta-methylbutyric acid | Val | Valine | L-Valine |