Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO− form under biological conditions), and a side chain isobutyl group, making it a non-polar aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Human dietary sources are foods that contain protein, such as meats, dairy products, soy products, and beans and other legumes. It is encoded by the codons UUA, UUG, CUU, CUC, CUA, and CUG.
Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production. Coenzyme A consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).
Transamination is a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential amino acids to non-essential amino acids.
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
β-Hydroxy β-methylbutyric acid (HMB), otherwise known as its conjugate base, β-hydroxyβ-methylbutyrate, is a naturally produced substance in humans that is used as a dietary supplement and as an ingredient in certain medical foods that are intended to promote wound healing and provide nutritional support for people with muscle wasting due to cancer or HIV/AIDS. In healthy adults, supplementation with HMB has been shown to increase exercise-induced gains in muscle size, muscle strength, and lean body mass, reduce skeletal muscle damage from exercise, improve aerobic exercise performance, and expedite recovery from exercise. Medical reviews and meta-analyses indicate that HMB supplementation also helps to preserve or increase lean body mass and muscle strength in individuals experiencing age-related muscle loss. HMB produces these effects in part by stimulating the production of proteins and inhibiting the breakdown of proteins in muscle tissue. No adverse effects from long-term use as a dietary supplement in adults have been found.
4-Hydroxyphenylpyruvate dioxygenase (HPPD), also known as α-ketoisocaproate dioxygenase, is an Fe(II)-containing non-heme oxygenase that catalyzes the second reaction in the catabolism of tyrosine - the conversion of 4-hydroxyphenylpyruvate into homogentisate. HPPD also catalyzes the conversion of phenylpyruvate to 2-hydroxyphenylacetate and the conversion of α-ketoisocaproate to β-hydroxy β-methylbutyrate. HPPD is an enzyme that is found in nearly all aerobic forms of life.
β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxybutyric acid is a chiral compound with two enantiomers: D-β-hydroxybutyric acid and L-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, D-β-hydroxybutyric acid is one of two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA2), a Gi/o-coupled G protein-coupled receptor (GPCR).
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).
Enoyl-CoA hydratase (ECH) or crotonase is an enzyme EC 4.2.1.17 that hydrates the double bond between the second and third carbons on 2-trans/cis-enoyl-CoA:
Methylcrotonyl CoA carboxylase is a biotin-requiring enzyme located in the mitochondria. MCC uses bicarbonate as a carboxyl group source to catalyze the carboxylation of a carbon adjacent to a carbonyl group performing the fourth step in processing leucine, an essential amino acid.
3-Hydroxy-3-methylglutaryl-CoA lyase is an enzyme (EC 4.1.3.4 that in human is encoded by the HMGCL gene located on chromosome 1. It is a key enzyme in ketogenesis. It is a ketogenic enzyme in the liver that catalyzes the formation of acetoacetate from HMG-CoA within the mitochondria. It also plays a prominent role in the catabolism of the amino acid leucine.
Branched-chain amino acid aminotransferase (BCAT), also known as branched-chain amino acid transaminase, is an aminotransferase enzyme (EC 2.6.1.42) which acts upon branched-chain amino acids (BCAAs). It is encoded by the BCAT2 gene in humans. The BCAT enzyme catalyzes the conversion of BCAAs and α-ketoglutarate into branched chain α-keto acids and glutamate.
3-Methylcrotonyl-CoA or β-Methylcrotonyl-CoA is an intermediate in the metabolism of leucine.
3-Methylglutaconyl-CoA (MG-CoA), also known as β-methylglutaconyl-CoA, is an intermediate in the metabolism of leucine. It is metabolized into HMG-CoA.
3-Methylglutaconyl-CoA hydratase, also known as MG-CoA hydratase and AUH, is an enzyme encoded by the AUH gene on chromosome 19. It is a member of the enoyl-CoA hydratase/isomerase superfamily, but it is the only member of that family that is able to bind to RNA. Not only does it bind to RNA, AUH has also been observed to be involved in the metabolic enzymatic activity, making it a dual-role protein. Mutations of this gene have been found to cause a disease called 3-Methylglutaconic Acuduria Type 1.
In enzymology, an isovaleryl-CoA dehydrogenase is an enzyme that catalyzes the chemical reaction
In molecular biology, hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase EC 2.3.3.10 is an enzyme which catalyzes the reaction in which acetyl-CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This reaction comprises the second step in the mevalonate-dependent isoprenoid biosynthesis pathway. HMG-CoA is an intermediate in both cholesterol synthesis and ketogenesis. This reaction is overactivated in patients with diabetes mellitus type 1 if left untreated, due to prolonged insulin deficiency and the exhaustion of substrates for gluconeogenesis and the TCA cycle, notably oxaloacetate. This results in shunting of excess acetyl-CoA into the ketone synthesis pathway via HMG-CoA, leading to the development of diabetic ketoacidosis.
α-Ketoisocaproic acid (α-KIC) and its conjugate base, α-ketoisocaproate, are metabolic intermediates in the metabolic pathway for L-leucine. Leucine is an essential amino acid, and its degradation is critical for many biological duties. 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. α-KIC is a key metabolite present in the urine of people with Maple syrup urine disease, along with other branched-chain amino acids. 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 ergogenicsupplements present as well. 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.
β-Hydroxy β-methylbutyryl-coenzyme A (HMB-CoA), also known as 3-hydroxyisovaleryl-CoA, is a metabolite of L-leucine that is produced in the human body. Its immediate precursors are β-hydroxy β-methylbutyric acid (HMB) and β-methylcrotonoyl-CoA (MC-CoA). It can be metabolized into HMB, MC-CoA, and HMG-CoA in humans.
