α-Ketoisocaproic acid
Chemical compound
From Wikipedia, the free encyclopedia
α-Ketoisocaproic acid (α-KIC), also known as 4-methyl-2-oxovaleric acid, and its conjugate base and carboxylate, α-ketoisocaproate, are metabolic intermediates in the metabolic pathway for L-leucine.[2] Leucine is an essential amino acid, and its degradation is critical for many biological duties.[3] α-KIC is produced in one of the first steps of the pathway by branched-chain amino acid aminotransferase by transferring the amine on L-leucine onto alpha ketoglutarate, and replacing that amine with a ketone. The degradation of L-leucine in the muscle to this compound allows for the production of the amino acids alanine and glutamate as well. In the liver, α-KIC can be converted to a vast number of compounds depending on the enzymes and cofactors present, including cholesterol, acetyl-CoA, isovaleryl-CoA, and other biological molecules. Isovaleryl-CoA is the main compound synthesized from ɑ-KIC.[2][4][5] α-KIC is a key metabolite present in the urine of people with Maple syrup urine disease, along with other branched-chain amino acids.[6] Derivatives of α-KIC have been studied in humans for their ability to improve physical performance during anaerobic exercise as a supplemental bridge between short-term and long-term exercise supplements. These studies show that α-KIC does not achieve this goal without other ergogenic supplements present as well.[7] α-KIC has also been observed to reduce skeletal muscle damage after eccentrically biased resistance exercises in people who do not usually perform those exercises.[8]
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| Names | |
|---|---|
| IUPAC name
4-Methyl-2-oxopentanoic acid | |
| Systematic IUPAC name
4-Methyl-2-oxopentanoic acid[1] | |
| Other names
4-Methyl-2-oxovaleric acid 2-Ketoisocaproic acid 2-Oxo-4-methylpentanoic acid 2-Oxo-4-methylvaleric acid 2-Oxoisocaproic acid 2-Oxoleucine Isobutylglyoxylic acid Ketoleucine α-Ketoisocapronic acid α-Oxoisocaproic acid | |
| Identifiers | |
3D model (JSmol) |
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| 1701823 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
| ECHA InfoCard | 100.011.304 |
| EC Number |
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| KEGG | |
| MeSH | Alpha-ketoisocaproic+acid |
PubChem CID |
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| UNII | |
| UN number | 3265 |
CompTox Dashboard (EPA) |
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| Properties | |
| C6H10O3 | |
| Molar mass | 130.143 g·mol−1 |
| Density | 1.055 g cm−3 (at 20 °C) |
| Melting point | 8 to 10 °C (46 to 50 °F; 281 to 283 K) |
| Boiling point | 85 °C (185 °F; 358 K) at 13 mmHg |
| log P | 0.133 |
| Acidity (pKa) | 2.651 |
| Basicity (pKb) | 11.346 |
| Hazards | |
| GHS labelling: | |
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| Danger | |
| H314 | |
| P260, P264, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Biological activity
Supplements
α-KIC has been studied as a nutritional supplement to aid in the performance of strenuous physical activity. Studies have shown that taking ɑ-KIC and its derivatives before acute physical activity led to an increase in muscle work by 10%, as well as a decrease in muscle fatigue during the early phase of the physical activity.[7] When taken with other supplements over a two-week period, such as beta-hydroxy beta-methylbutyrate (HMB), participants reported delayed onset of muscle soreness, as well as other positive effects such as increased muscle girth.[8] Studies have also suggested that ɑ-KIC taken alone did not have any significant positive impacts on physical performance, so it should be taken in conjunction with other ergogenic substances.[9] ɑ-KIC is not available as a supplement on its own, but its decarboxylated form HMB is available in calcium salt capsules or powder.[2]
Applications
The biochemical implications of α-KIC are largely connected to other biochemical pathways. Protein Synthesis, skeletal muscle regeneration, and skeletal muscle proteolysis have all been noted to change when ɑ-KIC is taken. There is not much research into the specific mechanisms taking part in these processes, but there is a noticeable correlation between ɑ-KIC ingestion and increased skeletal muscle protein synthesis, regeneration, and proteolysis.[2]
Toxicity
Multiple studies have demonstrated that there have been no adverse effects on humans nor animals that ingested α-KIC or HMB.[10][11]
In patients with maple syrup urine disease, who are unable to metabolize the branched chain alpha keto acids, α-KIC is believed to be one of the key mediators of neurotoxicity.[12]
Medical use
Branched-chain alpha-keto acids such as α-KIC are found in high concentrations in the urine of people who suffer from Maple Syrup Urine Disease. This is disease is caused by a partial branched-chain alpha-keto acid dehydrogenase deficiency, which leads to a buildup of branched-chain alpha-keto acids, including α-KIC and HMB.[13] These keto-acids build up in the liver,[2][4][5] and since limited isovaleryl-CoA can be produced, these keto-acids must be excreted in the urine as α-KIC, HMB, and many other similar keto acids. Flare-ups in people who have this condition are caused due to poor diet.[6] Symptoms of Maple Syrup Urine Disease include sweet smelling urine, irritability, lethargy, and in serious cases edema of the brain, apnea, coma, or respiratory failure.[13][6] Treatment includes lowering leucine intake and a specialized diet to make up for the lack of leucine ingestion.[6]
Leucine metabolism
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