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Nutrients Mar 2020L-histidine (HIS) is an essential amino acid with unique roles in proton buffering, metal ion chelation, scavenging of reactive oxygen and nitrogen species,... (Review)
Review
L-histidine (HIS) is an essential amino acid with unique roles in proton buffering, metal ion chelation, scavenging of reactive oxygen and nitrogen species, erythropoiesis, and the histaminergic system. Several HIS-rich proteins (e.g., haemoproteins, HIS-rich glycoproteins, histatins, HIS-rich calcium-binding protein, and filaggrin), HIS-containing dipeptides (particularly carnosine), and methyl- and sulphur-containing derivatives of HIS (3-methylhistidine, 1-methylhistidine, and ergothioneine) have specific functions. The unique chemical properties and physiological functions are the basis of the theoretical rationale to suggest HIS supplementation in a wide range of conditions. Several decades of experience have confirmed the effectiveness of HIS as a component of solutions used for organ preservation and myocardial protection in cardiac surgery. Further studies are needed to elucidate the effects of HIS supplementation on neurological disorders, atopic dermatitis, metabolic syndrome, diabetes, uraemic anaemia, ulcers, inflammatory bowel diseases, malignancies, and muscle performance during strenuous exercise. Signs of toxicity, mutagenic activity, and allergic reactions or peptic ulcers have not been reported, although HIS is a histamine precursor. Of concern should be findings of hepatic enlargement and increases in ammonia and glutamine and of decrease in branched-chain amino acids (valine, leucine, and isoleucine) in blood plasma indicating that HIS supplementation is inappropriate in patients with liver disease.
Topics: Amino Acids, Branched-Chain; Ammonia; Chelating Agents; Contraindications; Dermatitis, Atopic; Dietary Supplements; Filaggrin Proteins; Free Radical Scavengers; Glutamine; Histamine; Histidine; Humans; Hypertrophy; Liver; Liver Diseases; Metabolic Syndrome; Nervous System Diseases; Organ Preservation Solutions
PubMed: 32235743
DOI: 10.3390/nu12030848 -
Molecules (Basel, Switzerland) Feb 2023Ergothioneine, a sulfur-containing micromolecular histidine derivative, has attracted increasing attention from scholars since it was confirmed in the human body. In the... (Review)
Review
Ergothioneine, a sulfur-containing micromolecular histidine derivative, has attracted increasing attention from scholars since it was confirmed in the human body. In the human body, ergothioneine is transported and accumulated specifically through OCTN-1, especially in the mitochondria and nucleus, suggesting that it can target damaged cells and tissues as an antioxidant. It shows excellent antioxidant, anti-inflammatory effects, and anti-aging properties, and inhibits melanin production. It is a mega antioxidant that may participate in the antioxidant network system and promote the reducing glutathione regeneration cycle. This review summarizes studies on the antioxidant effects of ergothioneine on various free radicals in vitro to date and systematically introduces its biological activities and potential mechanisms, mostly in dermatology. Additionally, the application of ergothioneine in cosmetics is briefly summarized. Lastly, we propose some problems that require solutions to understand the mechanism of action of ergothioneine. We believe that ergothioneine has good prospects in the food and cosmetics industries, and can thus meet some needs of the health and beauty industry.
Topics: Humans; Antioxidants; Ergothioneine; Glutathione; Oxidative Stress; Histidine
PubMed: 36838636
DOI: 10.3390/molecules28041648 -
Genes Jan 2023Histidyl-tRNA synthetase (HARS) ligates histidine to its cognate transfer RNA (tRNA). Mutations in HARS cause the human genetic disorders Usher syndrome type 3B (USH3B)... (Review)
Review
Histidyl-tRNA synthetase (HARS) ligates histidine to its cognate transfer RNA (tRNA). Mutations in HARS cause the human genetic disorders Usher syndrome type 3B (USH3B) and Charcot-Marie-Tooth syndrome type 2W (CMT2W). Treatment for these diseases remains symptomatic, and no disease specific treatments are currently available. Mutations in can lead to destabilization of the enzyme, reduced aminoacylation, and decreased histidine incorporation into the proteome. Other mutations lead to a toxic gain-of-function and mistranslation of non-cognate amino acids in response to histidine codons, which can be rescued by histidine supplementation in vitro. We discuss recent advances in characterizing mutations and potential applications of amino acid and tRNA therapy for future gene and allele specific therapy.
Topics: Humans; Histidine; Mutation; Histidine-tRNA Ligase; Charcot-Marie-Tooth Disease; Aminoacylation
PubMed: 36833180
DOI: 10.3390/genes14020254 -
Molecular Cell Jun 2022Protein phosphorylation is a reversible post-translational modification. Nine of the 20 natural amino acids in proteins can be phosphorylated, but most of what we know... (Review)
Review
Protein phosphorylation is a reversible post-translational modification. Nine of the 20 natural amino acids in proteins can be phosphorylated, but most of what we know about the roles of protein phosphorylation has come from studies of serine, threonine, and tyrosine phosphorylation. Much less is understood about the phosphorylation of histidine, lysine, arginine, cysteine, aspartate, and glutamate, so-called non-canonical phosphorylations. Phosphohistidine (pHis) was discovered 60 years ago as a mitochondrial enzyme intermediate; since then, evidence for the existence of histidine kinases and phosphohistidine phosphatases has emerged, together with examples where protein function is regulated by reversible histidine phosphorylation. pHis is chemically unstable and has thus been challenging to study. However, the recent development of tools for studying pHis has accelerated our understanding of the multifaceted functions of histidine phosphorylation, revealing a large number of proteins that are phosphorylated on histidine and implicating pHis in a wide range of cellular processes.
Topics: Histidine; Phosphorylation; Phosphotyrosine; Proteins
PubMed: 35654043
DOI: 10.1016/j.molcel.2022.05.007 -
Chimia 2013Ergothioneine and ovothiol A are sulfur-containing histidine derivatives produced by microorganisms including Mycobacterium tuberculosis, Trypanosoma cruzi or Erwinia...
Ergothioneine and ovothiol A are sulfur-containing histidine derivatives produced by microorganisms including Mycobacterium tuberculosis, Trypanosoma cruzi or Erwinia amylovora and may also play important roles in human physiology. Based on our recent identification of thiohistidine biosynthetic enzymes from Mycobacterium smegmatis and Erwinia tasmaniensis we investigate several aspects of sulfur-based redox biochemistry. For example, we are characterizing the catalytic mechanism of two thiohistidine biosynthetic enzymes which afford O2-dependent sulfur insertion into the C(5)-H and C(2)-H bonds of the imidazolyl side chain of histidine.
Topics: Catalysis; Histidine; Ligases; Methylhistidines; Oxidation-Reduction; Safrole; Sulfhydryl Compounds
PubMed: 23863267
DOI: 10.2533/chimia.2013.333 -
The Journal of Nutrition Oct 2020Dietary supplementation of the amino acid histidine has demonstrable benefits in various clinical conditions. Recent work in a pediatric leukemia mouse model exposed a... (Review)
Review
Dietary supplementation of the amino acid histidine has demonstrable benefits in various clinical conditions. Recent work in a pediatric leukemia mouse model exposed a surprising potential application of histidine supplementation for cancer therapy enhancement. These findings demand a deeper reassessment of the physiological effects and potential drawbacks of histidine supplementation. As pertinent to this question, we discuss the safety of high doses of histidine and its relevant metabolic fates in the human body. We refrain from recommendations or final conclusions because comprehensive preclinical evidence for safety and efficacy of histidine supplementation is still lacking. However, we emphasize the incentive to study the safety of histidine supplementation and its potential to improve the clinical outcome of pediatric blood cancers through a simple dietary supplementation. The need for comprehensive preclinical testing of histidine supplementation in healthy and tumor-bearing mice is fundamental, and we hope that this review will facilitate such studies.
Topics: Animals; Dietary Supplements; Folic Acid; Formiminoglutamic Acid; Histidine; Humans; Leukemia; Methotrexate; Neoplasms
PubMed: 33000153
DOI: 10.1093/jn/nxaa132 -
Current Opinion in Structural Biology Dec 2020Ergothioneine is a sulfur-containing histidine derivative synthesized by many bacteria and most fungi but it also finds its way into human tissue by way of specific... (Review)
Review
Ergothioneine is a sulfur-containing histidine derivative synthesized by many bacteria and most fungi but it also finds its way into human tissue by way of specific absorption from the diet. The precise role of ergothioneine is not yet known but there is growing evidence that it plays a role as an antioxidant protecting human cells from oxidative stress and pathogenic bacteria from host defenses. In this review we highlight recent advances in understanding the structural basis of ergothioneine biosynthesis. In addition to unusual carbon-sulfur bond forming enzymology this research has revealed that ergothioneine biosynthesis has emerged at least three times by independent molecular evolution.
Topics: Enzymes; Ergothioneine; Histidine; Humans
PubMed: 32408082
DOI: 10.1016/j.sbi.2020.04.002 -
The Journal of Nutrition Oct 2020Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children. There is an unmet clinical need, particularly in... (Review)
Review
Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children. There is an unmet clinical need, particularly in children, for safe interventions that target the etiology of the disease. Deficiencies in the skin barrier protein, filaggrin (FLG) have been identified as major predisposing factors in AD. In mammals, l-histidine is rapidly incorporated into epidermal FLG and subsequent FLG proteolysis releases l-histidine as an important natural moisturizing factor (NMF). It has therefore been hypothesized that l-histidine supplementation would be a safe approach to augment both FLG and the NMF, enhance skin barrier function, and reduce AD severity. In a clinical pilot study, adult subjects (n = 24) with AD took either a placebo or 4 g oral l-histidine daily for 8 wk. Unlike the placebo, l-histidine reduced AD (34% reduction in SCORing Atopic Dermatitis scores; P < 0.003) after 4 wk. Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion. A survey of adults (n = 98) taking 4 g l-histidine daily reiterated a lack of causal AEs and also reported a 33% reduction in topical corticosteroid use. A placebo-controlled, clinical pilot study conducted in young children with AD (n = 49; mean age 3.5 y) taking 0.8 g l-histidine daily, showed that eczema area and severity index scores were reduced by 49% (P < 0.02) at 12 wk, whereas a placebo had no effect. The children taking l-histidine had 50 minor AEs (compared with 39 on placebo), with 78% considered as "not," 18% "unlikely," and 4% "possibly" related to l-histidine ingestion. These studies indicate that at the levels reported, oral l-histidine supplementation is well tolerated and has potential as a safe intervention for long-term use in the management of AD in all age groups.
Topics: Adult; Child, Preschool; Dermatitis, Atopic; Dietary Supplements; Eczema; Female; Filaggrin Proteins; Histidine; Humans; Male; Skin
PubMed: 33000160
DOI: 10.1093/jn/nxaa200 -
Biotechnology Advances 2022In the late 70's, the discovery of the restriction enzymes made possible the biological production of functional proteins by recombinant DNA technologies, a fact that... (Review)
Review
In the late 70's, the discovery of the restriction enzymes made possible the biological production of functional proteins by recombinant DNA technologies, a fact that largely empowered both biotechnological and pharmaceutical industries. Short peptides or small protein domains, with specific molecular affinities, were developed as purification tags in downstream processes to separate the target protein from the culture media or cell debris, upon breaking the producing cells. Among these tags, and by exploiting the interactivity of the imidazole ring of histidine residues, the hexahistidine peptide (H6) became a gold standard. Although initially used almost exclusively in protein production, H6 and related His-rich peptides are progressively proving a broad applicability in novel utilities including enzymatic processes, advanced drug delivery systems and diagnosis, through a so far unsuspected adaptation of their binding capabilities. In this context, the coordination of histidine residues and metals confers intriguing functionalities to His-rich sequences useable in the forward-thinking design of protein-based nano- and micro-materials and devices, through strategies that are comprehensively presented here.
Topics: Biotechnology; Histidine; Metals; Peptides; Proteins
PubMed: 34418503
DOI: 10.1016/j.biotechadv.2021.107817 -
Molecules (Basel, Switzerland) Apr 2022The history, chemistry, biology, and biosynthesis of the globally occurring histidine-derived alkaloids ergothioneine (), ovothiol A (), and selenoneine () are reviewed... (Review)
Review
The history, chemistry, biology, and biosynthesis of the globally occurring histidine-derived alkaloids ergothioneine (), ovothiol A (), and selenoneine () are reviewed comparatively and their significance to human well-being is discussed.
Topics: Alkaloids; Ergothioneine; Histidine; Humans; Methylhistidines; Organoselenium Compounds
PubMed: 35566030
DOI: 10.3390/molecules27092673