98-529: HMB may refer to: Compounds [ edit ] β-Hydroxy β-methylbutyric acid , (CH 3 ) 2 C(OH)CH 2 COOH , a metabolite of the essential amino acid leucine, synthesized in the human body Human Melanoma Black , a monoclonal antibody Languages [ edit ] Humburi Senni language , spoken in Burkina Faso and Mali Places [ edit ] Half Moon Bay, California , city in
196-541: A diagnostic biomarker , particularly in the case of metabolic disorders . The following table lists some of these disorders along with the associated HMB concentrations detected in urine or blood plasma. The first reported chemical synthesis of HMB was published in 1877 by the Russian chemists Michael and Alexander Zaytsev . HMB was isolated from the bark of Erythrophleum couminga (a Madagascan tree) in 1941 by Leopold Ružička . The earliest reported isolation of HMB as
294-403: A high-protein diet . Clinical trials that used HMB for the treatment of muscle wasting have involved the administration of 3 grams of HMB per day under different dosing regimens. According to one review, an optimal dosing regimen is to administer it in one 1 gram dose, three times a day, since this ensures elevated plasma concentrations of HMB throughout the day; however, as of 2016
392-401: A meta-analysis of seven randomized controlled trials , HMB supplementation can preserve or increase lean muscle mass and muscle strength in sarcopenic older adults. HMB does not appear to significantly affect fat mass in older adults. Preliminary clinical evidence suggests that HMB supplementation may also prevent muscle atrophy during bed rest . A growing body of evidence supports
490-437: A polysome , this enables simultaneous synthesis of multiple identical polypeptide chains. Termination of the growing polypeptide chain occurs when the ribosome encounters a stop codon (UAA, UAG, or UGA) in the mRNA molecule. When this occurs, no tRNA can recognise it and a release factor induces the release of the complete polypeptide chain from the ribosome. Dr. Har Gobind Khorana , a scientist originating from India, decoded
588-449: A gene – to unwind, separating the two DNA strands and exposing a series of bases. Despite DNA being a double-stranded molecule, only one of the strands acts as a template for pre-mRNA synthesis; this strand is known as the template strand. The other DNA strand (which is complementary to the template strand) is known as the coding strand. Both DNA and RNA have intrinsic directionality , meaning there are two distinct ends of
686-425: A human metabolite was by Tanaka and coworkers in 1968 from a patient with isovaleric acidemia . The effects of HMB on human skeletal muscle were first discovered by Steven L. Nissen at Iowa State University in the mid-1990s . Nissen founded a company called Metabolic Technologies, Inc. (MTI) around the time of his discovery, which later acquired six HMB-related patents that the company has used to license
784-401: A lysine amino acid by the enzyme acetyltransferase . The acetyl group is removed from a donor molecule known as acetyl coenzyme A and transferred onto the target protein. Histones undergo acetylation on their lysine residues by enzymes known as histone acetyltransferase . The effect of acetylation is to weaken the charge interactions between the histone and DNA, thereby making more genes in
882-453: A mature mRNA molecule. There are 3 key steps within post-transcriptional modifications: The 5' cap is added to the 5' end of the pre-mRNA molecule and is composed of a guanine nucleotide modified through methylation . The purpose of the 5' cap is to prevent break down of mature mRNA molecules before translation, the cap also aids binding of the ribosome to the mRNA to start translation and enables mRNA to be differentiated from other RNAs in
980-456: A medical food and the Revigor brand of HMB as an active ingredient in food products (e.g., certain formulations of Ensure) and other medical foods (e.g., certain formulations of Juven). Protein synthesis Protein biosynthesis (or protein synthesis ) is a core biological process, occurring inside cells , balancing the loss of cellular proteins (via degradation or export ) through
1078-425: A medical professional. Juven, a nutrition product which contains 3 grams of HMB-Ca , 14 grams of L -arginine , and 14 grams of L -glutamine per two servings, has been shown to improve lean body mass during clinical trials in individuals with AIDS and cancer, but not rheumatoid cachexia . Further research involving the treatment of cancer cachexia with Juven over a period of several months
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#17328474494441176-459: A protein while, exons are nucleotide sequences that directly encode a protein. Introns and exons are present in both the underlying DNA sequence and the pre-mRNA molecule, therefore, to produce a mature mRNA molecule encoding a protein, splicing must occur. During splicing, the intervening introns are removed from the pre-mRNA molecule by a multi-protein complex known as a spliceosome (composed of over 150 proteins and RNA). This mature mRNA molecule
1274-432: A protein, known as a gene , is converted into a template molecule called messenger RNA (mRNA). This conversion is carried out by enzymes, known as RNA polymerases , in the nucleus of the cell . In eukaryotes, this mRNA is initially produced in a premature form ( pre-mRNA ) which undergoes post-transcriptional modifications to produce mature mRNA . The mature mRNA is exported from the cell nucleus via nuclear pores to
1372-422: A sequence of covalently bonded amino acids. The primary structure of a protein is encoded by a gene. Therefore, any changes to the sequence of the gene can alter the primary structure of the protein and all subsequent levels of protein structure, ultimately changing the overall structure and function. The primary structure of a protein (the polypeptide chain) can then fold or coil to form the secondary structure of
1470-472: A small fraction of HMB's metabolic precursor, L -leucine , is metabolized into HMB, pharmacologically active concentrations of the compound in blood plasma and muscle can only be achieved by supplementing HMB directly. A healthy adult produces approximately 0.3 grams per day, while supplemental HMB is usually taken in doses of 3–6 grams per day. HMB is sold at a cost of about US$ 30–50 per month when taken in doses of 3 grams per day. HMB
1568-460: A specific DNA sequence which terminates transcription, RNA polymerase detaches and pre-mRNA synthesis is complete. The pre-mRNA molecule synthesized is complementary to the template DNA strand and shares the same nucleotide sequence as the coding DNA strand. However, there is one crucial difference in the nucleotide composition of DNA and mRNA molecules. DNA is composed of the bases: guanine , cytosine , adenine and thymine (G, C, A and T). RNA
1666-439: A study where participants consumed 2.42 grams of pure HMB-FA while fasting, the average plasma HMB concentration increased from a basal level of 5.1 μM to 408 μM after 30 minutes. At 150 minutes post-ingestion, the average plasma HMB concentration among participants was 275 μM. Abnormal HMB concentrations in urine and blood plasma have been noted in several disease states where it may serve as
1764-496: A tendency to form dense protein clumps , which are often implicated in diseases, particularly neurological disorders including Alzheimer's and Parkinson's disease . Transcription occurs in the nucleus using DNA as a template to produce mRNA . In eukaryotes , this mRNA molecule is known as pre-mRNA as it undergoes post-transcriptional modifications in the nucleus to produce a mature mRNA molecule. However, in prokaryotes post-transcriptional modifications are not required so
1862-424: A year. Studies on young adults taking 6 grams of HMB per day for up to 2 months have also reported no adverse effects. Studies with supplemental HMB on young, growing rats and livestock have reported no adverse effects based upon clinical chemistry or observable characteristics; for humans younger than 18, there is limited data on the safety of supplemental HMB. The human equivalent dose of HMB for
1960-452: Is 25–40% higher than for HMB-Ca. The fraction of an ingested dose that is excreted in urine does not differ between the two forms. After ingestion, HMB-Ca is converted to β-hydroxy β-methylbutyrate following dissociation of the calcium moiety in the gut. When the HMB-Ca dosage form is ingested, the magnitude and time at which the peak plasma concentration of HMB occurs depends on
2058-595: Is 1.42. β-Hydroxy β-methylbutyric acid is a member of the carboxylic acid family of organic compounds . It is a structural analog of butyric acid with a hydroxyl functional group and a methyl substituent located on its beta carbon . By extension, other structural analogs include β-hydroxybutyric acid and β-methylbutyric acid . A variety of synthetic routes to β-hydroxy β-methylbutyric acid have been developed. The first reported chemical syntheses approached HMB by oxidation of alkene , vicinal diol , and alcohol precursors: Depending on
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#17328474494442156-410: Is a multi-subunit complex composed of multiple folded, polypeptide chain subunits e.g. haemoglobin . There are events that follow protein biosynthesis such as proteolysis and protein-folding. Proteolysis refers to the cleavage of proteins by proteases and the breakdown of proteins into amino acids by the action of enzymes. When protein folding into the mature, functional 3D state is complete, it
2254-442: Is a group of diseases caused by a mutation in a subunit of hemoglobin, a protein found in red blood cells responsible for transporting oxygen. The most dangerous of the sickle cell diseases is known as sickle cell anemia. Sickle cell anemia is the most common homozygous recessive single gene disorder , meaning the affected individual must carry a mutation in both copies of the affected gene (one inherited from each parent) to experience
2352-517: Is a reducing environment. Many diseases are caused by mutations in genes, due to the direct connection between the DNA nucleotide sequence and the amino acid sequence of the encoded protein. Changes to the primary structure of the protein can result in the protein mis-folding or malfunctioning. Mutations within a single gene have been identified as a cause of multiple diseases, including sickle cell disease , known as single gene disorders. Sickle cell disease
2450-592: Is affected by the time that it is used relative to exercise. The greatest reduction in skeletal muscle damage from a single bout of exercise has been shown to occur when HMB-Ca is ingested 1–2 hours prior to exercise or HMB-FA is ingested 30–60 minutes prior to exercise. In 2006, only about 2% of college student athletes in the United States used HMB as a dietary supplement. As of 2017, HMB has found widespread use as an ergogenic supplement among athletes. As of 2018, HMB has not been banned by
2548-420: Is also composed of four bases: guanine, cytosine, adenine and uracil . In RNA molecules, the DNA base thymine is replaced by uracil which is able to base pair with adenine. Therefore, in the pre-mRNA molecule, all complementary bases which would be thymine in the coding DNA strand are replaced by uracil. Once transcription is complete, the pre-mRNA molecule undergoes post-transcriptional modifications to produce
2646-609: Is also contained in several nutritional products and medical foods marketed by Abbott Laboratories (e.g., certain formulations of Ensure and Juven ), and is present in insignificant quantities in certain foods, such as alfalfa , asparagus , avocados , cauliflower , grapefruit , and catfish . Supplemental HMB has been used in clinical trials as a treatment for preserving lean body mass in muscle wasting conditions, particularly sarcopenia , and has been studied in clinical trials as an adjunct therapy in conjunction with resistance exercise . Based upon two medical reviews and
2744-617: Is also present in insignificant quantities in certain foods, such as alfalfa , asparagus , avocados , cauliflower , grapefruit , and catfish . The effects of HMB on human skeletal muscle were first discovered by Steven L. Nissen at Iowa State University in the mid-1990s . As of 2018, HMB has not been banned by the National Collegiate Athletic Association , World Anti-Doping Agency , or any other prominent national or international athletic organization. In 2006, only about 2% of college student athletes in
2842-418: Is covalently added to the target protein by glycosyltransferases enzymes and modified by glycosidases in the endoplasmic reticulum and Golgi apparatus . Glycosylation can have a critical role in determining the final, folded 3D structure of the target protein. In some cases glycosylation is necessary for correct folding. N-linked glycosylation promotes protein folding by increasing solubility and mediates
2940-1068: Is different from Wikidata All article disambiguation pages All disambiguation pages Beta-Hydroxy beta-methylbutyric acid β-Hydroxy β-methylbutyric acid ( HMB ), otherwise known as its conjugate base , β-hydroxy β-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
3038-453: Is eliminated via the kidneys , with roughly 10–40% of an ingested dose being excreted unchanged in urine. The remaining 60–90% of the dose is retained in tissues or excreted as HMB metabolites. The fraction of a given dose of HMB that is excreted unchanged in urine increases with the dose. The metabolism of HMB is catalyzed by an uncharacterized enzyme which converts it to β-hydroxy β-methylbutyryl-CoA ( HMB-CoA ). HMB-CoA
HMB - Misplaced Pages Continue
3136-683: Is initially catalyzed by the branched-chain amino acid aminotransferase enzyme, producing α-ketoisocaproate (α-KIC). α-KIC is mostly metabolized by the mitochondrial enzyme branched-chain α-ketoacid dehydrogenase , which converts it to isovaleryl-CoA . Isovaleryl-CoA is subsequently metabolized by isovaleryl-CoA dehydrogenase and converted to MC-CoA , which is used in the synthesis of acetyl-CoA and other compounds. During biotin deficiency , HMB can be synthesized from MC-CoA via enoyl-CoA hydratase and an unknown thioesterase enzyme, which convert MC-CoA into HMB-CoA and HMB-CoA into HMB respectively. A relatively small amount of α-KIC
3234-409: Is mediated through the phosphorylation of Akt , a serine/threonine-specific protein kinase . The free acid ( HMB-FA ) and monohydrated calcium salt ( HMB-Ca ) forms of HMB have different pharmacokinetics . HMB-FA is more readily absorbed into the bloodstream and has a longer elimination half-life (3 hours) relative to HMB-Ca (2.5 hours). Tissue uptake and utilization of HMB-FA
3332-478: Is metabolized by either enoyl-CoA hydratase or another uncharacterized enzyme, producing β-methylcrotonyl-CoA ( MC-CoA ) or hydroxymethylglutaryl-CoA ( HMG-CoA ) respectively. MC-CoA is then converted by the enzyme methylcrotonyl-CoA carboxylase to methylglutaconyl-CoA ( MG-CoA ), which is subsequently converted to HMG-CoA by methylglutaconyl-CoA hydratase . HMG-CoA is then cleaved into acetyl-CoA and acetoacetate by HMG-CoA lyase or used in
3430-417: Is metabolized in the liver by the cytosolic enzyme 4-hydroxyphenylpyruvate dioxygenase (KIC dioxygenase), which converts α-KIC to HMB. In healthy individuals, this minor pathway – which involves the conversion of L -leucine to α-KIC and then HMB – is the predominant route of HMB synthesis. β-Hydroxy β-methylbutyric acid is a monocarboxylic β-hydroxy acid and natural product with
3528-460: Is not necessarily the end of the protein maturation pathway. A folded protein can still undergo further processing through post-translational modifications. There are over 200 known types of post-translational modification, these modifications can alter protein activity, the ability of the protein to interact with other proteins and where the protein is found within the cell e.g. in the cell nucleus or cytoplasm. Through post-translational modifications,
3626-490: Is paired with the new codon. In the case of sickle cell anemia, the most common missense mutation is a single nucleotide mutation from thymine to adenine in the hemoglobin B subunit gene. This changes codon 6 from encoding the amino acid glutamic acid to encoding valine. This change in the primary structure of the hemoglobin B subunit polypeptide chain alters the functionality of the hemoglobin multi-subunit complex in low oxygen conditions. When red blood cells unload oxygen into
3724-620: Is readily available from the aldol condensation of acetone. An organometallic approach to HMB involves the carboxylation of tert -butyl alcohol with carbon monoxide and Fenton's reagent ( hydrogen peroxide and ferrous iron ). Alternatively, HMB can be prepared through microbial oxidation of β-methylbutyric acid by the fungus Galactomyces reessii . The concentration of naturally produced HMB has been measured in several human body fluids using nuclear magnetic resonance spectroscopy , liquid chromatography–mass spectrometry , and gas chromatography–mass spectrometry methods. In
3822-746: Is required to adequately determine treatment efficacy. With an appropriate exercise program, dietary supplementation with 3 grams of HMB per day has been shown to increase exercise-induced gains in muscle size, muscle strength and power, and lean body mass, reduce exercise-induced skeletal muscle damage, and expedite recovery from high-intensity exercise. Based upon limited clinical research, HMB supplementation may also improve aerobic exercise performance and increase gains in aerobic fitness when combined with high-intensity interval training . These effects of HMB are more pronounced in untrained individuals and athletes who perform high intensity resistance or aerobic exercise. In resistance-trained populations,
3920-485: Is the reversible addition of a methyl group onto an amino acid catalyzed by methyltransferase enzymes. Methylation occurs on at least 9 of the 20 common amino acids, however, it mainly occurs on the amino acids lysine and arginine . One example of a protein which is commonly methylated is a histone . Histones are proteins found in the nucleus of the cell. DNA is tightly wrapped round histones and held in place by other proteins and interactions between negative charges in
4018-429: Is the start codon composed of the nucleotides AUG. The correct tRNA with the anticodon (complementary 3 nucleotide sequence UAC) binds to the mRNA using the ribosome. This tRNA delivers the correct amino acid corresponding to the mRNA codon, in the case of the start codon, this is the amino acid methionine. The next codon (adjacent to the start codon) is then bound by the correct tRNA with complementary anticodon, delivering
HMB - Misplaced Pages Continue
4116-441: Is then exported into the cytoplasm through nuclear pores in the envelope of the nucleus. During translation, ribosomes synthesize polypeptide chains from mRNA template molecules. In eukaryotes, translation occurs in the cytoplasm of the cell, where the ribosomes are located either free floating or attached to the endoplasmic reticulum . In prokaryotes, which lack a nucleus, the processes of both transcription and translation occur in
4214-420: The National Collegiate Athletic Association , World Anti-Doping Agency , or any other prominent national or international athletic organization. The safety profile of HMB in adult humans is based upon evidence from clinical trials in humans and animal studies . In humans, no adverse effects in young adults or older adults have been reported when HMB is taken in doses of 3 grams per day for up to
4312-452: The cytoplasm of the cell for translation to occur. During translation, the mRNA is read by ribosomes which use the nucleotide sequence of the mRNA to determine the sequence of amino acids . The ribosomes catalyze the formation of covalent peptide bonds between the encoded amino acids to form a polypeptide chain . Following translation the polypeptide chain must fold to form a functional protein; for example, to function as an enzyme
4410-418: The mechanistic target of rapamycin (mTOR) and subsequent activation of mTORC1 Tooltip mechanistic target of rapamycin complex 1 , which leads to protein biosynthesis in cellular ribosomes via phosphorylation of mTORC1's immediate targets (i.e., the p70S6 kinase and the translation repressor protein 4EBP1 ). Supplementation with HMB in several non-human animal species has been shown to increase
4508-480: The molecular formula C 5 H 10 O 3 . At room temperature, pure β-hydroxy β-methylbutyric acid occurs as a transparent, colorless to light yellow liquid which is soluble in water. β-Hydroxy β-methylbutyric acid is a weak acid with a p K a of 4.4. Its refractive index ( n 25°C λ = 589 n m {\displaystyle {\mathit {n}}_{\text{25°C}}^{\mathrm {\lambda =589nm} }} )
4606-469: The no-observed-adverse-effect level (NOAEL) that was identified in a rat model is approximately 0.4 g/kg of body weight per day. Two animal studies have examined the effects of HMB supplementation in pregnant pigs on the offspring and reported no adverse effects on the fetus. No clinical testing with supplemental HMB has been conducted on pregnant women, and pregnant and lactating women are advised not to take HMB by Metabolic Technologies, Inc. ,
4704-401: The pre-existing structure of the protein. Disulfide bonds are formed in an oxidation reaction between two thiol groups and therefore, need an oxidizing environment to react. As a result, disulfide bonds are typically formed in the oxidizing environment of the endoplasmic reticulum catalyzed by enzymes called protein disulfide isomerases. Disulfide bonds are rarely formed in the cytoplasm as it
4802-420: 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. HMB is sold as a dietary supplement at a cost of about US$ 30–50 per month when taking 3 grams per day. HMB is also contained in several nutritional products, including certain formulations of Ensure and Juven . HMB
4900-413: The serum concentration of growth hormone and insulin-like growth factor 1 (IGF-1) via an unknown mechanism, in turn promoting protein synthesis through increased mTOR phosphorylation. Based upon limited clinical evidence in humans, supplemental HMB appears to increase the secretion of growth hormone and IGF-1 in response to resistance exercise. As of 2016 , the signaling cascade that mediates
4998-480: The ubiquitin–proteasome system in skeletal muscle and by inhibiting apoptosis of skeletal muscle nuclei via unidentified mechanisms. Based upon animal studies, HMB appears to be metabolized within skeletal muscle into cholesterol , which may then be incorporated into the muscle cell membrane , thereby enhancing membrane integrity and function. The effects of HMB on muscle protein metabolism may help stabilize muscle cell structure. One review suggested that
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#17328474494445096-455: The 3D protein structure, covalent bonds are formed either within the protein or between the different polypeptide chains in the quaternary structure. The most prevalent type is a disulfide bond (also known as a disulfide bridge). A disulfide bond is formed between two cysteine amino acids using their side chain chemical groups containing a Sulphur atom, these chemical groups are known as thiol functional groups. Disulfide bonds act to stabilize
5194-414: The 5'-to-3' direction by catalysing the formation of phosphodiester bonds between activated nucleotides (free in the nucleus) that are capable of complementary base pairing with the template strand. Behind the moving RNA polymerase the two strands of DNA rejoin, so only 12 base pairs of DNA are exposed at one time. RNA polymerase builds the pre-mRNA molecule at a rate of 20 nucleotides per second enabling
5292-415: The DNA accessible for transcription. The final, prevalent post-translational chemical group modification is phosphorylation. Phosphorylation is the reversible, covalent addition of a phosphate group to specific amino acids ( serine , threonine and tyrosine ) within the protein. The phosphate group is removed from the donor molecule ATP by a protein kinase and transferred onto the hydroxyl group of
5390-431: The DNA and positive charges on the histone. A highly specific pattern of amino acid methylation on the histone proteins is used to determine which regions of DNA are tightly wound and unable to be transcribed and which regions are loosely wound and able to be transcribed. Histone-based regulation of DNA transcription is also modified by acetylation. Acetylation is the reversible covalent addition of an acetyl group onto
5488-533: The DRAM of the host machine His/Her Magesty's Barque Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title HMB . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=HMB&oldid=1098741118 " Category : Disambiguation pages Hidden categories: Short description
5586-454: The HMB-induced reduction in muscle protein breakdown has not been identified in living humans, although it is well-established that it attenuates proteolysis in humans in vivo . Unlike L -leucine , HMB attenuates muscle protein breakdown in an insulin -independent manner in humans. HMB is believed to reduce muscle protein breakdown in humans by inhibiting the 19S and 20S subunits of
5684-511: The RNA sequences for about 20 amino acids. He was awarded the Nobel prize in 1968, along with two other scientists, for his work. Once synthesis of the polypeptide chain is complete, the polypeptide chain folds to adopt a specific structure which enables the protein to carry out its functions. The basic form of protein structure is known as the primary structure , which is simply the polypeptide chain i.e.
5782-644: The United States Sports [ edit ] Historical medieval battles , a modern sport Other [ edit ] Hawkeye Marching Band , the marching band for the University of Iowa HabibMetro , a Swiss multinational bank in Pakistan Heavy menstrual bleeding , a menstrual condition Host Memory Buffer, an optional feature in version 1.2 of the NVMe specification, which allows SSDs to utilize
5880-419: The United States used HMB as a dietary supplement. As of 2017, HMB has found widespread use as an ergogenic supplement among young athletes. HMB is sold as an over-the-counter dietary supplement in the free acid form, β-hydroxy β-methylbutyric acid (HMB-FA), and as a monohydrated calcium salt of the conjugate base , calcium β-hydroxy β-methylbutyrate monohydrate (HMB-Ca, CaHMB). Since only
5978-405: The ability of the protein to bind its substrate. Post-translational modifications can incorporate more complex, large molecules into the folded protein structure. One common example of this is glycosylation , the addition of a polysaccharide molecule, which is widely considered to be most common post-translational modification. In glycosylation, a polysaccharide molecule (known as a glycan )
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#17328474494446076-483: The best dosing regimen for muscle wasting conditions is still being investigated. Some branded products that contain HMB (i.e., certain formulations of Ensure and Juven) are medical foods that are intended to be used to provide nutritional support under the care of a doctor in individuals with muscle wasting due to HIV/AIDS or cancer , to promote wound healing following surgery or injury, or when otherwise recommended by
6174-480: The blood plasma and cerebrospinal fluid (CSF) of healthy adults, the average molar concentration of HMB has been measured at 4.0 micromolar (μM). The average concentration of HMB in the intramuscular fluid of healthy men of ages 21–23 has been measured at 7.0 μM. In the urine of healthy individuals of any age, the excreted urinary concentration of HMB has been measured in a range of 0–68 micromoles per millimole (μmol/mmol) of creatinine . In
6272-434: The breast milk of healthy lactating women, HMB and L -leucine have been measured in ranges of 42–164 μg/L and 2.1–88.5 mg/L. In comparison, HMB has been detected and measured in the milk of healthy cows at a concentration of <20–29 μg/L. This concentration is far too low to be an adequate dietary source of HMB for obtaining pharmacologically active concentrations of the compound in blood plasma. In
6370-458: The cell. In contrast, the 3' Poly(A) tail is added to the 3' end of the mRNA molecule and is composed of 100-200 adenine bases. These distinct mRNA modifications enable the cell to detect that the full mRNA message is intact if both the 5' cap and 3' tail are present. This modified pre-mRNA molecule then undergoes the process of RNA splicing. Genes are composed of a series of introns and exons , introns are nucleotide sequences which do not encode
6468-425: The company that grants licenses to include HMB in dietary supplements, due to a lack of safety studies. Several components of the signaling cascade that mediates the HMB-induced increase in human skeletal muscle protein synthesis have been identified in vivo . Similar to HMB's metabolic precursor , L -leucine , HMB has been shown to increase protein synthesis in human skeletal muscle via phosphorylation of
6566-442: The correct amino acids to the ribosome. Each tRNA is composed of 70-80 nucleotides and adopts a characteristic cloverleaf structure due to the formation of hydrogen bonds between the nucleotides within the molecule. There are around 60 different types of tRNAs, each tRNA binds to a specific sequence of three nucleotides (known as a codon ) within the mRNA molecule and delivers a specific amino acid. The ribosome initially attaches to
6664-407: The correct anticodon complementary to the third codon is selected, delivering the next amino acid to the ribosome which is covalently joined to the growing polypeptide chain. This process continues with the ribosome moving along the mRNA molecule adding up to 15 amino acids per second to the polypeptide chain. Behind the first ribosome, up to 50 additional ribosomes can bind to the mRNA molecule forming
6762-465: The cytoplasm. Ribosomes are complex molecular machines , made of a mixture of protein and ribosomal RNA , arranged into two subunits (a large and a small subunit), which surround the mRNA molecule. The ribosome reads the mRNA molecule in a 5'-3' direction and uses it as a template to determine the order of amino acids in the polypeptide chain. To translate the mRNA molecule, the ribosome uses small molecules, known as transfer RNAs (tRNA), to deliver
6860-411: The disease. Hemoglobin has a complex quaternary structure and is composed of four polypeptide subunits – two A subunits and two B subunits. Patients with sickle cell anemia have a missense or substitution mutation in the gene encoding the hemoglobin B subunit polypeptide chain. A missense mutation means the nucleotide mutation alters the overall codon triplet such that a different amino acid
6958-504: The diversity of proteins encoded by the genome is expanded by 2 to 3 orders of magnitude . There are four key classes of post-translational modification: Cleavage of proteins is an irreversible post-translational modification carried out by enzymes known as proteases . These proteases are often highly specific and cause hydrolysis of a limited number of peptide bonds within the target protein. The resulting shortened protein has an altered polypeptide chain with different amino acids at
7056-432: The dose and concurrent food intake. Higher HMB-Ca doses increase the rate of absorption , resulting in a peak plasma HMB level ( C max ) that is disproportionately greater than expected of a linear dose-response relationship and which occurs sooner relative to lower doses. Consumption of HMB-Ca with sugary substances slows the rate of HMB absorption, resulting in a lower peak plasma HMB level that occurs later. HMB
7154-540: The effects of HMB on muscle strength and lean body mass are limited. HMB affects muscle size, strength, mass, power, and recovery in part by stimulating myofibrillar muscle protein synthesis and inhibiting muscle protein breakdown through various mechanisms, including the activation of mechanistic target of rapamycin complex 1 (mTORC1) and inhibition of proteasome -mediated proteolysis in skeletal muscles. The efficacy of HMB supplementation for reducing skeletal muscle damage from prolonged or high-intensity exercise
7252-461: The efficacy of HMB in nutritional support for reducing, or even reversing, the loss of muscle mass, muscle function , and muscle strength that occurs in hypercatabolic disease states such as cancer cachexia ; consequently, the authors of two 2016 reviews of the clinical evidence recommended that the prevention and treatment of sarcopenia and muscle wasting in general include supplementation with HMB, regular resistance exercise, and consumption of
7350-441: The experimental conditions, cycloaddition of acetone and ketene produces either β-isovalerolactone or 4,4-dimethyloxetan-2-one, both of which hydrolyze under basic conditions to yield the conjugate base of HMB. The haloform reaction provides another pathway to HMB involving the exhaustive halogenation of the methyl-ketone region of diacetone alcohol with sodium hypobromite or sodium hypochlorite ; Diacetone alcohol
7448-531: The individual. Cancers form as a result of gene mutations as well as improper protein translation. In addition to cancer cells proliferating abnormally, they suppress the expression of anti-apoptotic or pro-apoptotic genes or proteins. Most cancer cells see a mutation in the signaling protein Ras, which functions as an on/off signal transductor in cells. In cancer cells, the RAS protein becomes persistently active, thus promoting
7546-409: The mRNA at the start codon (AUG) and begins to translate the molecule. The mRNA nucleotide sequence is read in triplets ; three adjacent nucleotides in the mRNA molecule correspond to a single codon. Each tRNA has an exposed sequence of three nucleotides, known as the anticodon, which are complementary in sequence to a specific codon that may be present in mRNA. For example, the first codon encountered
7644-421: The mRNA encoded amino acid sequence. Mutations can cause the polypeptide chain to be shorter by generating a stop sequence which causes early termination of translation. Alternatively, a mutation in the mRNA sequence changes the specific amino acid encoded at that position in the polypeptide chain. This amino acid change can impact the protein's ability to function or to fold correctly. Misfolded proteins have
7742-405: The mature mRNA molecule is immediately produced by transcription. Initially, an enzyme known as a helicase acts on the molecule of DNA. DNA has an antiparallel , double helix structure composed of two, complementary polynucleotide strands, held together by hydrogen bonds between the base pairs. The helicase disrupts the hydrogen bonds causing a region of DNA – corresponding to
7840-417: The molecule. This property of directionality is due to the asymmetrical underlying nucleotide subunits, with a phosphate group on one side of the pentose sugar and a base on the other. The five carbons in the pentose sugar are numbered from 1' (where ' means prime) to 5'. Therefore, the phosphodiester bonds connecting the nucleotides are formed by joining the hydroxyl group on the 3' carbon of one nucleotide to
7938-435: The next amino acid to ribosome. The ribosome then uses its peptidyl transferase enzymatic activity to catalyze the formation of the covalent peptide bond between the two adjacent amino acids. The ribosome then moves along the mRNA molecule to the third codon. The ribosome then releases the first tRNA molecule, as only two tRNA molecules can be brought together by a single ribosome at one time. The next complementary tRNA with
8036-425: The nitrogen in an asparagine amino acid. In contrast, O-linked glycosylation is the sequential covalent addition of individual sugars onto the oxygen in the amino acids serine and threonine within the mature protein structure. Many proteins produced within the cell are secreted outside the cell to function as extracellular proteins. Extracellular proteins are exposed to a wide variety of conditions. To stabilize
8134-450: The observed HMB-induced reduction in the plasma concentration of muscle damage biomarkers (i.e., muscle enzymes such as creatine kinase and lactate dehydrogenase ) in humans following intense exercise may be due to a cholesterol-mediated improvement in muscle cell membrane function. HMB has been shown to stimulate the proliferation , differentiation , and fusion of human myosatellite cells in vitro , which potentially increases
8232-406: The phosphate group on the 5' carbon of another nucleotide. Hence, the coding strand of DNA runs in a 5' to 3' direction and the complementary, template DNA strand runs in the opposite direction from 3' to 5'. The enzyme RNA polymerase binds to the exposed template strand and reads from the gene in the 3' to 5' direction. Simultaneously, the RNA polymerase synthesizes a single strand of pre-mRNA in
8330-485: The polypeptide chain must fold correctly to produce a functional active site . To adopt a functional three-dimensional shape, the polypeptide chain must first form a series of smaller underlying structures called secondary structures . The polypeptide chain in these secondary structures then folds to produce the overall 3D tertiary structure . Once correctly folded, the protein can undergo further maturation through different post-translational modifications , which can alter
8428-423: The production of cholesterol via the mevalonate pathway . HMB is synthesized in the human body through the metabolism of L -leucine , a branched-chain amino acid . In healthy individuals, approximately 60% of dietary L -leucine is metabolized after several hours, with roughly 5% ( 2–10% range) of dietary L -leucine being converted to HMB. The vast majority of L -leucine metabolism
8526-399: The production of new proteins. Proteins perform a number of critical functions as enzymes , structural proteins or hormones . Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences. Protein synthesis can be divided broadly into two phases: transcription and translation . During transcription, a section of DNA encoding
8624-424: The production of thousands of pre-mRNA molecules from the same gene in an hour. Despite the fast rate of synthesis, the RNA polymerase enzyme contains its own proofreading mechanism. The proofreading mechanisms allows the RNA polymerase to remove incorrect nucleotides (which are not complementary to the template strand of DNA) from the growing pre-mRNA molecule through an excision reaction. When RNA polymerases reaches
8722-487: The proliferation of the cell due to the absence of any regulation. Additionally, most cancer cells carry two mutant copies of the regulator gene p53, which acts as a gatekeeper for damaged genes and initiates apoptosis in malignant cells. In its absence, the cell cannot initiate apoptosis or signal for other cells to destroy it. As the tumor cells proliferate, they either remain confined to one area and are called benign, or become malignant cells that migrate to other areas of
8820-495: The protein binding to protein chaperones . Chaperones are proteins responsible for folding and maintaining the structure of other proteins. There are broadly two types of glycosylation, N-linked glycosylation and O-linked glycosylation . N-linked glycosylation starts in the endoplasmic reticulum with the addition of a precursor glycan. The precursor glycan is modified in the Golgi apparatus to produce complex glycan bound covalently to
8918-406: The protein's ability to function, its location within the cell (e.g. cytoplasm or nucleus) and its ability to interact with other proteins . Protein biosynthesis has a key role in disease as changes and errors in this process, through underlying DNA mutations or protein misfolding , are often the underlying causes of a disease. DNA mutations change the subsequent mRNA sequence, which then alters
9016-411: The protein. The most common types of secondary structure are known as an alpha helix or beta sheet , these are small structures produced by hydrogen bonds forming within the polypeptide chain. This secondary structure then folds to produce the tertiary structure of the protein. The tertiary structure is the proteins overall 3D structure which is made of different secondary structures folding together. In
9114-492: The regenerative capacity of skeletal muscle, by increasing the protein expression of certain myogenic regulatory factors (e.g., myoD and myogenin ) and gene transcription factors (e.g., MEF2 ). HMB-induced human myosatellite cell proliferation in vitro is mediated through the phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2 . HMB-induced human myosatellite differentiation and accelerated fusion of myosatellite cells into muscle tissue in vitro
9212-439: The right to manufacture and incorporate HMB into dietary supplements. When it first became available commercially in the late 1990s, HMB was marketed solely as an exercise supplement to help athletes and bodybuilders build muscle. MTI subsequently developed two HMB-containing products, Juven and Revigor, to which Abbott Nutrition obtained the market rights in 2003 and 2008 respectively. Since then, Abbott has marketed Juven as
9310-465: The start and end of the chain. This post-translational modification often alters the proteins function, the protein can be inactivated or activated by the cleavage and can display new biological activities. Following translation, small chemical groups can be added onto amino acids within the mature protein structure. Examples of processes which add chemical groups to the target protein include methylation, acetylation and phosphorylation . Methylation
9408-424: The target amino acid, this produces adenosine diphosphate as a byproduct. This process can be reversed and the phosphate group removed by the enzyme protein phosphatase . Phosphorylation can create a binding site on the phosphorylated protein which enables it to interact with other proteins and generate large, multi-protein complexes. Alternatively, phosphorylation can change the level of protein activity by altering
9506-415: The tertiary structure, key protein features e.g. the active site, are folded and formed enabling the protein to function. Finally, some proteins may adopt a complex quaternary structure . Most proteins are made of a single polypeptide chain, however, some proteins are composed of multiple polypeptide chains (known as subunits) which fold and interact to form the quaternary structure. Hence, the overall protein
9604-456: The tissues of the body, the mutated haemoglobin protein starts to stick together to form a semi-solid structure within the red blood cell. This distorts the shape of the red blood cell, resulting in the characteristic "sickle" shape, and reduces cell flexibility. This rigid, distorted red blood cell can accumulate in blood vessels creating a blockage. The blockage prevents blood flow to tissues and can lead to tissue death which causes great pain to
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