Singapore Drugs Database

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

Under FDA approval, fish oil pharmaceuticals are typically products consisting of a combination of the omega-3-fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are indicated primarily as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia [FDA Label, F36]. Under EMA approval, such fish oil pharmaceuticals comprised of virtually the same fish and fish oil derived omega-3-fatty acids EPA and DHA are indicated specifically for (a) adjuvant treatment in secondary prevention after myocardial infarction, in addition to other standard therapy (ie. statins, antiplatelet medicinal products, beta blockers, ACE inhibitors), and (b) as a supplement to diet when dietary measures alone are insufficient to produce an adequate response, particularly with type IV hypertriglyceridemia in monotherapy or type IIb/III in combination with statins, when control of triglycerides is insufficient [L2661]. In addition, prescribing information for EMA approved fish oil pharmaceuticals are also indicated as an adjunct to diet to reduce very high (>=500 mg/dL) triglyceride levels in adult patients, much like similar FDA approved indications [F37, FDA Label].

Mechanism of Action

The specific mechanism of action by which the fish oil EPA and DHA acids are capable of reducing serum triglyceride levels is not yet fully understood [FDA Label, A32933]. Nevertheless, it is proposed that such omega-3-fatty acids may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase that participates in the generation of triglycerides; that they might interact with nuclear transcription factors that manage lipogenesis; or that their presence and increase in levels can cause cellular metabolism to subsequently shift toward a decrease in triglyceride synthesis and an increase in fatty acid oxidation [A32933]. Moreover, the EPA and DHA acids are also believed to be able to promote apolipoprotein B degradation in the liver through the stimulation of an autophagic process [A32933]. It may also be possible that these fish oil acids can accelerate the clearance of very-low-density lipoprotein (VLDL) particles and chylomicron [A32933]. The combination of all these actions results in fewer VLDL particles being assembled and secreted, which is of considerable importance as VLDL particles are the major endogenous source of triglycerides [A32933]. Moreover, new paradigms of how inflammation is contained and dissipated involve various newly discovered chemical mediators, resolvins, and protectins [A32933]. Such agents are believed to be directly involved in blocking neutrophil migration, infiltration, recruitment, as well as blocking T-cell migration and promoting T-cell apoptosis [A32933]. Additionally, such protectins can also reduce tumor necrosis factor and interferon secretion [A32933]. Of particular importance, however, is the fact that protectins and resolvins are exclusively derived from omega-3-fatty acids and that EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins [A32933]. It is believed that these effects of such fish oil acids underlie the actions that fish oil have demonstrated on eliciting stability for vulnerable inflammatory plaques [A32933]. Finally, fish oil acids have demonstrated certain direct electrophysiological effects on the myocardium [A32933]. In animal studies, it was shown that the ventricular fibrillation threshold could be increased in both animals fed or infused with omega-3-fatty acids [A32933]. Further studies subsequently revealed that such fatty acids could reduce both sodium currents and L-type calcium currents on a cellular and ion channel level [A32933]. It is consequently hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current could reduce arrhythmogenic depolarizing currents - and that perhaps the use of EPA and DHA fish oil acids could facilitate such activity [A32933]. For the time being, however, omega-3-fatty acids in pharmaceutical supplement form have not been shown to elicit such protection against heart conditions [L2662].

Pharmacokinetics

Absorption

The absorption process of fish oil EPA and DHA acids have been documented as being very efficient, with an absorption rate of about 95%, which is similar to that of other ingested fats [L784].

Distribution

The volume of distribution of EPA is documented as being approximately 82 L [A18890] while that of DHA is about 8,216 ml/kg in male rat animal models [A32918].

Metabolism

During and after absorption there are three main pathways for the metabolism of the fish oil omega-3-fatty acids: (a) the acids are transported to the liver where they are incorporated into various categories of lipoproteins and then channeled to the peripheral lipid stores, or (b) the cell membrane phospholipids are replaced by lipoprotein phospholipids and the fatty acids can then act as precursors for various eicosanoids, or (c) the majority of the fatty acids are oxidised to meet energy requirements [F33, L2661]. The concentration of the EPA and DHA fish oil omega-3-fatty acids in the plasma phospholipids corresponds to the EPA and DHA incorporated into the cell membranes [F33, L2661]. Ultimately, animal pharmacokinetic studies have shown that there is a complete hydrolysis of the ethyl ester accompanied by satisfactory absorption and incorporation of EPA and DHA into the plasma phospholipids and cholesterol esters [L2661].

Elimination

Clearance

The clearance of EPA is recorded to be about 548 ml/hr while that of DHA is documented to be about 518 ml/hr hours [FDA Label].

Toxicity

There have been some concerns that high doses of DHA and/or EPA (in the range of 900mg/day or EPA plus 600 mg/day of DHA or more for several weeks) could potentially reduce an individual's immune function due to the suppression of inflammatory responses [L784]. However, according to the European Food Safety Authority, long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe [L784]. Commonly reported side effects of omega-3 supplements are usually mild [L784]. These include unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat [L784].

Active Ingredient/Synonyms

Fish oil containing omega-3 acids | Fish oils | Omega-3 fish oil | Fish oil |

Indication

Glucose pharmaceutical formulations (oral tablets, injections) are indicated for caloric supply and carbohydrate supplementation in case of nutrient deprivation. It is also used for metabolic disorders such as hypoglycemia.[L787]

Mechanism of Action

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate.[A19402] The addition of the high-energy phosphate group activates glucose for the subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where the total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated by hexokinase.[T35] Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number, and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation to preserve cellular and whole body metabolic integrity.[A19401]

Pharmacokinetics

Absorption

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation.[A19395] SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion.[A19400] Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.[A19406]

Distribution

The mean volume of distribution after intravenous infusion is 10.6L.[A19407]

Metabolism

Glucose can undergo aerobic oxidation in conjunction with the synthesis of energy molecules. Glycolysis is the initial stage of glucose metabolism where one glucose molecule is degraded into two molecules of pyruvate via substrate-level phosphorylation. These products are transported to the mitochondria where they are further oxidized into oxygen and carbon dioxide.[A19402]

Elimination

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglycemia.[A19408]

Toxicity

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and solute overloading resulting in dilution of the serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.[L786]

Active Ingredient/Synonyms

aldehydo-D-glucose | Anhydrous dextrose | D-Glucose in linear form | D-glucose, anhydrous | D(+)-Glucose | Dextrose anhydrous | Dextrose, anhydrous | Glucose | Glucose anhydrous | Glucose, anhydrous | D-glucose |

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

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

Supplemental L-lysine has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Mechanism of Action

Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to L-lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine.

Pharmacokinetics

Absorption

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

Distribution

Metabolism

Hepatic

Elimination

Active Ingredient/Synonyms

(S)-2,6-diaminohexanoic acid | (S)-lysine | (S)-α,ε-diaminocaproic acid | 6-ammonio-L-norleucine | L-2,6-Diaminocaproic acid | L-lys | L-Lysin | LYS | Lysina | Lysine | Lysine acid | Lysinum | L-Lysine |

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

For use in adults as a source of calories and fatty acids in total parenteral nutrition [FDA Label]. Sometimes used as an additive in cosmetic products.

Mechanism of Action

Fatty acids act as a substrate in energy production through beta-oxidation as well as important components of cell membrane structures and prescursors for bioactive molecules like prostaglandins [FDA Label].

Toxicity

Fat overload sydrome is the primary form of toxicity characterized by a sudden deterioration in the patient's condition accompanied by fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, liver fatty infiltration, deteriorating liver function, and central nervous system manifestations such as coma [FDA Label]. The precise cause of this is unclear. While it is most likely to occur during overdosage of lipids some occurences have been reported when lipids are administered appropriately. Intraperitoneal LD50 in mice of >50g/kg and intravenous LD50 in rats of 1320mg/kg [L857].

Active Ingredient/Synonyms

Olive oil | Olive oil |

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

The use of diet supplements containing taurine is indicated for the nutritional support of infants and young pediatric patients requiring total parenteral nutrition via central or peripheral routes. The usage of diet supplements containing taurine prevents nitrogen and weight loss or to treat negative nitrogen balance in pediatric patients where the alimentary tract cannot be done through oral, gastrostomy or jejunostomy administration, there is impaired gastrointestinal absorption or protein requirements are substantially increased.[FDA label]

Mechanism of Action

The diet supplements containing taurine function by replacing the missing nutriments in the body. Taurine, as a single agent, presents different functions like substrate for formation of bile salts, cell volume regulation, modulation of intracellular calcium, cytoprotection of central nervous system, etc.[A31398]

Pharmacokinetics

Absorption

Oral administration of taurine was studied and it reported dose-dependent values of AUC, Cmax and tmax wherein a dose of 1-30 mg/kg ranged from 89-3452 mcg min/L, 2-15.7 mcg min/ml and 15 min respectively.[A31399] Further studies in healthy individuals gave an AUC, Cmax and tmax in the range of 116-284.5 mg h/L, 59-112.6 mg/L and 1-2.5 h.[A31400]

Distribution

The distribution of taurine was studied under the two-compartment model and each one of the compartments gave a range for the volume of distribution of 299-353 ml/kg in compartment 1 and 4608-8374 ml/kg in compartment 2 in mice.[A31399] Further studies in healthy indivudals gave a volume of distribution that ranged from 19.8 to 40.7 L.[A31400]

Metabolism

Taurine can be metabolized by diverse organisms to form different types of metabolites derived from the original form of taurine. In the human, the pathways that form the metabolism of taurine are divided in the formation of 5-glutamyl-taurine by the action of the enzyme gamma-glutamyltransferase 6 or the formation of taurocholate by the action of the bile acid-CoA:amino acid N-acyltransferase.[L1060]

Elimination

Clearance

The clearance rate of orally administered taurine was reported to be dose-dependent wherein a dose of 1 mg/kg it presents a clearance rate of 11.7 ml min/kg, 10 mg/kg generates a clearance rate of 18.7 ml min/kg and a dose of 30 mg/kg reports a clearance rate of 9.4 ml min/kg.[A31399] Further studies in healthy individuals generate a clearance rate that ranged from 14 to 34.4 L/h.[A31400]

Toxicity

The administration of taurine has been correlatefd to significant in the hypothalamus and the modification of neuroendocrine functions. Other than that, taurine administration in regular doses is reported by different articles and institutions to be safe.[A31406]

Active Ingredient/Synonyms

Aminoethylsulfonic acid | Taurineold | Taurine |

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

When incorporated as an active ingredient in combination with other active components like fish oils, soya oil, and olive oil as a prescription medication (SMOFLIPID), medium chain triglycerides (MCTs) constitute a therapy indicated for supplying energy, calories, and essential fatty acids to adult patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient, or contraindicated [F126, F127]. However, given the predominant indication of MCTs for acting as a source of calories and essential fatty acids, the use of MCTs alone or as a component part of various unique, individual patient-tailored composite regimen therapies, MCTs are also ultimately indicated for a wide range of health conditions that involve energy deficiency, malnutrition, or disturbances in the ordinary absorption of dietary fats [A33175, F128]. Such conditions can include Crohn's disease, Waldmann disease, weight maintenance in AIDS, cachexia, and various disturbances in patient bile secretion (like cholestasis, disturbances in hepatic-intestinal circulation of bile acids, intestinal dysbacteriosis), or in pancreatic lipase secretion (like pancreatic failure in the course of cystic fibrosis) [A33175, F128].

Mechanism of Action

Absorption of larger long-chain triglycerides (LCT) requires specific processing in the digestive tract, like emulsification with bile [A33175]. This process is aimed at obtaining the maximum surface for digestion (lipolysis with breakage of ester bonds of triglycerides and with the release of monoglycerides, free fatty acids, and glycerol) [A33175]. The process of digestion of fats occurs largely in the duodenum and initial segment of the jejunum [A33175]. Lipases are found in the pancreatic juice and the brush border [A33175]. Once the aforementioned bonds are broken and the fatty acids and monoglycerides are absorbed into an enterocyte, they undergo resynthesis to triglycerides, in the presence of ligase, co-enzyme A, and ATP. Chylomicrons are formed. They get to the lymph and only then can they be transported to blood and destination organs [A33175]. Release of fats from chylomicrons requires the presence of plasmatic lipases, and only then can they be metabolised or stored as a reserve in the fatty tissue [A33175]. Conversely, hydrolysis of medium chain triglycerides (MCTs, which is faster than LCT hydrolysis anyway) does not require bile and lipase [A33175]. Without hydrolysis, they may also be absorbed by the enterocytes and they do not require re-esterification [A33175]. From enterocytes they are directly absorbed into the portal vein and then transported mainly to the liver. Thus, absorption of MCT is faster than that of LCTs [A33175]. Their metabolism is facilitated as well because they are metabolised by the liver almost completely (only when the liver’s metabolic abilities are exceeded the process is taken over by peripheral tissues) with energy release, regardless of the presence of carnitine (which is necessary for the transport of long-chain fatty acids through the mitochondrial membrane) [A33175]. Thanks to this the availability of medium-chain fatty acids for mitochondrial oxidation is better [A33175]. This means that MCT are an easy and quick source of energy [A33175]. However, it should be borne in mind that quantities of MCT exceeding the abilities of the liver are metabolised peripherally in a carnitine-dependent mechanism, which can increase the demand for it [A33175]. On the other hand, it has been observed that on the enterohormonal pathway (an important element of which is a MCT-induced increase of the YY peptide concentration and a decrease in cholecystokinin release) MCT cause a decrease of appetite and consequently a decrease in energy intake [A33175]. They also interfere with the metabolism of the fatty tissue, by hindering the creation of a deposit from long chain acids [A33175]. It has been proven that an MCT-enriched diet modulates metabolism of fats, which is manifested as a decrease in the concentration of triglycerides and cholesterol [A33175]. Moreover, unlike LCT, MCT do not affect the release of cholecystokinin or the emptying of the gallbladder and they do not increase the secretion of pancreatic enzymes [A33175]. They can speed up the intestinal passage by affecting the release of the YY peptide, but only in the distal sections of the intestine [A33175]. Moreover, it has been found that MCT facilitate absorption of calcium [A33175].

Pharmacokinetics

Absorption

The absorption of medium chain triglycerides is considered rapid [A33175, L2895, F126, F127, F128] but that both long-chain triglycerides and medium chain triglycerides share a similar absorption, which is an absorption rate of about 95% - similar to that of other ingested fats [L784].

Distribution

The apparent volumes of distribution have been researched as approximately 4.5 L for medium chain triglycerides and 19 L for medium chain fatty acids in a typical 70-kg subject [A33174].

Metabolism

In capillaries, both medium chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are hydrolysed by lipoprotein lipase to glycerol and free fatty acids, and medium chain fatty acids (MCFAs) and long chain fatty acids (LCFAs), respectively [F126]. MCTs are hydrolysed at a faster rate than LCTs and therefore have a faster elimination rate [F126]. Free MCFAs then readily enter the liver, kidney, heart and other peripheral organs where they are oxidised by β-oxidation and the citric acid cycle to carbon dioxide and water [F126]. Alternatively, via the ketogenesis pathway, the β-oxidation of fatty acids generates the acetyl-CoA that can lead to the formation of ketone bodies like acetoacetate and β-hydroxybutyrate [F126].

Elimination

Clearance

The clearance of medium chain triglycerides in healthy control subjects was measured to be about 1.93 +/- 0.34 mL.kg-1.min-1 [A33179].

Toxicity

The excess use of medium chain triglycerides (MCTs) can lead to increased plasma levels of medium chain dicarboxylic acids, 3-hydroxy fatty acids and ketone bodies [F126]. Hyperketonaemia was observed in repeat-dose toxicity studies with SMOFLIPID [F126]. If excess MCTs are administered, the capacity of extrahepatic tissues to use ketone bodies is saturated and this may be of particular concern in some diabetes patients [F126]. The increased level of ketone bodies aggravates metabolic acidosis and accelerates the breakdown of homeostatic mechanisms [F126].

Active Ingredient/Synonyms

Caprylic/capric triglyceride | Caprylic/capric triglycerides | Coconut oil, fractioned | Fractionated coconut oil | Fractionated triglyceride of coconut oil | MCT | Medium chain triglyceride | Medium-chain glycerides | Triglycerides, medium-chain | Medium-chain triglycerides |

Indication

When incorporated as an active ingredient in combination with other active components like fish oils, soya oil, and olive oil as a prescription medication (SMOFLIPID), medium chain triglycerides (MCTs) constitute a therapy indicated for supplying energy, calories, and essential fatty acids to adult patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient, or contraindicated [F126, F127]. However, given the predominant indication of MCTs for acting as a source of calories and essential fatty acids, the use of MCTs alone or as a component part of various unique, individual patient-tailored composite regimen therapies, MCTs are also ultimately indicated for a wide range of health conditions that involve energy deficiency, malnutrition, or disturbances in the ordinary absorption of dietary fats [A33175, F128]. Such conditions can include Crohn's disease, Waldmann disease, weight maintenance in AIDS, cachexia, and various disturbances in patient bile secretion (like cholestasis, disturbances in hepatic-intestinal circulation of bile acids, intestinal dysbacteriosis), or in pancreatic lipase secretion (like pancreatic failure in the course of cystic fibrosis) [A33175, F128].

Mechanism of Action

Absorption of larger long-chain triglycerides (LCT) requires specific processing in the digestive tract, like emulsification with bile [A33175]. This process is aimed at obtaining the maximum surface for digestion (lipolysis with breakage of ester bonds of triglycerides and with the release of monoglycerides, free fatty acids, and glycerol) [A33175]. The process of digestion of fats occurs largely in the duodenum and initial segment of the jejunum [A33175]. Lipases are found in the pancreatic juice and the brush border [A33175]. Once the aforementioned bonds are broken and the fatty acids and monoglycerides are absorbed into an enterocyte, they undergo resynthesis to triglycerides, in the presence of ligase, co-enzyme A, and ATP. Chylomicrons are formed. They get to the lymph and only then can they be transported to blood and destination organs [A33175]. Release of fats from chylomicrons requires the presence of plasmatic lipases, and only then can they be metabolised or stored as a reserve in the fatty tissue [A33175]. Conversely, hydrolysis of medium chain triglycerides (MCTs, which is faster than LCT hydrolysis anyway) does not require bile and lipase [A33175]. Without hydrolysis, they may also be absorbed by the enterocytes and they do not require re-esterification [A33175]. From enterocytes they are directly absorbed into the portal vein and then transported mainly to the liver. Thus, absorption of MCT is faster than that of LCTs [A33175]. Their metabolism is facilitated as well because they are metabolised by the liver almost completely (only when the liver’s metabolic abilities are exceeded the process is taken over by peripheral tissues) with energy release, regardless of the presence of carnitine (which is necessary for the transport of long-chain fatty acids through the mitochondrial membrane) [A33175]. Thanks to this the availability of medium-chain fatty acids for mitochondrial oxidation is better [A33175]. This means that MCT are an easy and quick source of energy [A33175]. However, it should be borne in mind that quantities of MCT exceeding the abilities of the liver are metabolised peripherally in a carnitine-dependent mechanism, which can increase the demand for it [A33175]. On the other hand, it has been observed that on the enterohormonal pathway (an important element of which is a MCT-induced increase of the YY peptide concentration and a decrease in cholecystokinin release) MCT cause a decrease of appetite and consequently a decrease in energy intake [A33175]. They also interfere with the metabolism of the fatty tissue, by hindering the creation of a deposit from long chain acids [A33175]. It has been proven that an MCT-enriched diet modulates metabolism of fats, which is manifested as a decrease in the concentration of triglycerides and cholesterol [A33175]. Moreover, unlike LCT, MCT do not affect the release of cholecystokinin or the emptying of the gallbladder and they do not increase the secretion of pancreatic enzymes [A33175]. They can speed up the intestinal passage by affecting the release of the YY peptide, but only in the distal sections of the intestine [A33175]. Moreover, it has been found that MCT facilitate absorption of calcium [A33175].

Pharmacokinetics

Absorption

The absorption of medium chain triglycerides is considered rapid [A33175, L2895, F126, F127, F128] but that both long-chain triglycerides and medium chain triglycerides share a similar absorption, which is an absorption rate of about 95% - similar to that of other ingested fats [L784].

Distribution

The apparent volumes of distribution have been researched as approximately 4.5 L for medium chain triglycerides and 19 L for medium chain fatty acids in a typical 70-kg subject [A33174].

Metabolism

In capillaries, both medium chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are hydrolysed by lipoprotein lipase to glycerol and free fatty acids, and medium chain fatty acids (MCFAs) and long chain fatty acids (LCFAs), respectively [F126]. MCTs are hydrolysed at a faster rate than LCTs and therefore have a faster elimination rate [F126]. Free MCFAs then readily enter the liver, kidney, heart and other peripheral organs where they are oxidised by β-oxidation and the citric acid cycle to carbon dioxide and water [F126]. Alternatively, via the ketogenesis pathway, the β-oxidation of fatty acids generates the acetyl-CoA that can lead to the formation of ketone bodies like acetoacetate and β-hydroxybutyrate [F126].

Elimination

Clearance

The clearance of medium chain triglycerides in healthy control subjects was measured to be about 1.93 +/- 0.34 mL.kg-1.min-1 [A33179].

Toxicity

The excess use of medium chain triglycerides (MCTs) can lead to increased plasma levels of medium chain dicarboxylic acids, 3-hydroxy fatty acids and ketone bodies [F126]. Hyperketonaemia was observed in repeat-dose toxicity studies with SMOFLIPID [F126]. If excess MCTs are administered, the capacity of extrahepatic tissues to use ketone bodies is saturated and this may be of particular concern in some diabetes patients [F126]. The increased level of ketone bodies aggravates metabolic acidosis and accelerates the breakdown of homeostatic mechanisms [F126].

Active Ingredient/Synonyms

Caprylic/capric triglyceride | Caprylic/capric triglycerides | Coconut oil, fractioned | Fractionated coconut oil | Fractionated triglyceride of coconut oil | MCT | Medium chain triglyceride | Medium-chain glycerides | Triglycerides, medium-chain | Medium-chain triglycerides |

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

Tyrosine is claimed to act as an effective antidepressant, however results are mixed. Tyrosine has also been claimed to reduce stress and combat narcolepsy and chronic fatigue, however these claims have been refuted by some studies.

Mechanism of Action

Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%. The mechanism of L-tyrosine's antidepressant activity can be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.

Pharmacokinetics

Absorption

L-tyrosine is absorbed from the small intestine by a sodium-dependent active transport process.

Distribution

Metabolism

In the liver, L-tyrosine is involved in a number of biochemical reactions, including protein synthesis and oxidative catabolic reactions. L-tyrosine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body.

Elimination

Toxicity

L-Tyrosine has very low toxicity. There have been very few reports of toxicity. LD₅₀ (oral, rat) > 5110 mg/kg.

Active Ingredient/Synonyms

(−)-α-amino-p-hydroxyhydrocinnamic acid | (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid | (S)-(-)-Tyrosine | (S)-2-Amino-3-(p-hydroxyphenyl)propionic acid | (S)-3-(p-Hydroxyphenyl)alanine | (S)-alpha-amino-4-Hydroxybenzenepropanoic acid | (S)-Tyrosine | (S)-α-amino-4-hydroxybenzenepropanoic acid | 4-hydroxy-L-phenylalanine | L-Tyrosin | Tyr | Tyrosine | Y | L-Tyrosine |

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 |