• The most well-established human function of tetrahydrobiopterin (BH4) is as the cofactor for phenylalanine-4-hydroxylase (PAH), tyrosine-3-hydroxylase, and tryptophan-5-hydroxylase. (medscape.com)
  • Tetrahydrobiopterin deficiencies are disorders that affect phenylalanine (Phe) homeostasis, as well as brain biosynthesis of catecholamine, serotonin, and (occasionally) nitric oxide. (medscape.com)
  • Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs). (wikipedia.org)
  • Tryptophan is a poor substrate for tyrosine hydroxylase, however it can hydroxylate L-phenylalanine to form L-tyrosine and small amounts of 3-hydroxyphenylalanine. (wikipedia.org)
  • Tetrahydrobiopterin (BH4) is a natural and essential cofactor for the enzymatic hydroxylation of phenylalanine (Phe) and tyrosine (Tyr), and for two tryptophan hydroxylases, three nitric oxide synthases, and glyceryl-ether monooxygenase. (thieme-connect.de)
  • Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. (bvsalud.org)
  • The latter two are key enzymes in biogenic amine biosynthesis (ie, aromatic amino acid synthesis). (medscape.com)
  • Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. (wikipedia.org)
  • These disorders cause hyperphenylalaninemia and impaired synthesis of serotonin and dopamine since tyrosine hydroxylase and neuronal tryptophan hydroxylase require BH4 and serotonin/dopamine products (5-hydroxytryptophan and L-dopa). (thieme-connect.de)
  • Tryptophan (TRP) is an essential dietary amino acid that, unless otherwise committed to protein synthesis, undergoes metabolism via the Tryptophan-Kynurenine (TRP-KYN) pathway in vertebrate organisms. (mdpi.com)
  • BACKGROUND: Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. (bvsalud.org)
  • Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. (bvsalud.org)
  • These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation. (bvsalud.org)
  • In addition to hydroxylating aromatic amino acids, BH4 serves as the cofactor for nitric oxide synthase and glyceryl-ether mono-oxygenase. (medscape.com)
  • In cases of such stress, it was observed that BH4 itself, sepiapterin, folic acid, resveratrol, and a small-molecular-weight compound AVE3085 have the ability to recouple endothelial nitric oxide synthase (eNOS) and improve endothelial function. (medscape.com)
  • [ 12 ] BH4 deficiency converts neuronal nitric oxide synthase (NOS) into an efficient peroxynitrite synthase, which is responsible for the increase in neuronal vulnerability to hypoxia-induced mitochondrial damage and necrosis. (medscape.com)
  • CONCLUSIONS: The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. (bvsalud.org)
  • One of the oxygen atoms in O2 is used to hydroxylate the tyrosine molecule to obtain L-DOPA and the other one is used to hydroxylate the cofactor. (wikipedia.org)
  • Like the other aromatic amino acid hydroxylases (AAAHs), tyrosine hydroxylase use the cofactor tetrahydrobiopterin (BH4) under normal conditions, although other similar molecules may also work as a cofactor for tyrosine hydroxylase. (wikipedia.org)
  • These biochemical reactions frequently involve cofactors, often vitamins, which help the specific enzyme function, e.g. vitamin B 6 is the cofactor for the enzyme cystathionine β synthase which converts the amino acid homocysteine into cystathionine. (oncohemakey.com)
  • A pair of principal enzymes, glutamate dehydrogenase and glutamine synthatase, are found in all organisms and effect the conversion of ammonia into the amino acids glutamate and glutamine, respectively. (medmuv.com)
  • Substrate specificity of catechol oxidase from Lycopus europaeus and characterization of the bioproducts of enzymic caffeic acid oxidation. (lookformedical.com)
  • BH4 deficiencies are grouped with phenylketonuria (PKU), which is an inborn error of protein metabolism that results from an impaired ability to metabolize the essential amino acid Phe. (medscape.com)
  • The gold standard treatment of severe disorders of BH4 metabolism is based on replacement therapy with BH4, 5-hydroxytryptophan, L-dopa, and carbidopa, with the addition, in certain cases, of folinic acid supplements and pramipexole. (thieme-connect.de)
  • 3 Longo N. Disorders of biopterin metabolism. (thieme-connect.de)
  • Figure 17.1 illustrates the metabolic processes involved in the overall metabolism of carbohydrates, fats and protein including the catabolic processes to produce energy and urea (the product of the detoxification of the nitrogen moiety of amino acids) and anabolic processes to form tissue protein and energy stores, glycogen and lipids. (oncohemakey.com)
  • Thiamin pyrophosphate plays a key role in the stabilization of the acyl carbanion synthon in carbohydrate and amino acid metabolism. (tamu.edu)
  • Dopamine may be converted into norepinephrine by the enzyme dopamine β-hydroxylase, which can be further modified by the enzyme phenylethanol N-methyltransferase to obtain epinephrine. (wikipedia.org)
  • Since L-DOPA is the precursor for the neurotransmitters dopamine, noradrenaline and adrenaline, tyrosine hydroxylase is therefore found in the cytosol of all cells containing these catecholamines. (wikipedia.org)
  • Dietary fats, and lipids produced endogenously from acetyl-CoA, are initially hydrolysed by lipases into glycerol and free fatty acids. (oncohemakey.com)
  • RESULTS: Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. (bvsalud.org)
  • To produce energy G-6-PO 4 (derived from monosaccharides from dietary CHO or produced from glycogen degradation by glycogenolysis) is converted by a series of enzyme reactions in the glycolytic pathway to form pyruvate or lactic acid, then to acetyl-CoA, which is also produced from fatty acid oxidation and degradation of the carbon skeleton of glucogenic amino acids ( Table 17.1 ). (oncohemakey.com)
  • Dietary fat is present mainly as long chain triglycerides, comprising a glycerol backbone and fatty acids. (oncohemakey.com)
  • Dietary protein is broken down into 20 individual amino acids for absorption. (oncohemakey.com)
  • Reduced nitrogen enters the human body as dietary free amino acids, protein, and the ammonia produced by intestinal tract bacteria. (medmuv.com)
  • Tyrosine hydroxylase may also be involved in other reactions as well, such as oxidizing L-DOPA to form 5-S-cysteinyl-DOPA or other L-DOPA derivatives. (wikipedia.org)
  • Catabolism is the breakdown of large complex molecules to provide energy for cellular activity and smaller compounds, e.g. amino acids, needed for anabolic reactions or for elimination from the body. (oncohemakey.com)
  • Some product of these reactions are utilized for other purposes (thus salvaging a portion of the amino nitrogen), while others are excreted. (medmuv.com)
  • Amino and amide groups from these 2 substances are freely transferred to other carbon skeletons by transamination and transamidation reactions. (medmuv.com)
  • G-6-PO 4 can also be produced via pyruvate from protein catabolism of glucogenic amino acids ( Table 17.1 ) or breakdown of glycerol from lipids (gluconeogenesis). (oncohemakey.com)
  • In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose. (bvsalud.org)
  • Tryptophan (Trp) is an essential proteinogenic amino acid and metabolic precursor for several signaling molecules that has been implicated in many physiological and pathological processes. (bvsalud.org)
  • Nitrogen fixation is carried out by bacterial nitrogenases forming reduced nitrogen, NH4+ which can then be used by all organisms to form amino acids. (medmuv.com)
  • In humans, tyrosine hydroxylase is encoded by the TH gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. (wikipedia.org)
  • Urine appears to be the major route of excretion, with a urine:fecal ratio of approximately 3:1 in humans. (cdc.gov)
  • Fatty acids enter the mitochondria via the carnitine transport cycle (medium chain fatty acids enter independently of carnitine) into the β-oxidation spiral in which fatty acids, via a series of enzymes, produce acetyl-CoA and electron carriers. (oncohemakey.com)
  • Chuaiphichai et al (2017) demonstrated for the first time that selective deficiency in endothelial cell BH4 biosynthesis, via targeted deletion of gene GCHL , is enough to cause eNOS uncoupling, which leads to impaired vascular function in resistance arteries, even without vascular disease. (medscape.com)
  • Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. (bvsalud.org)
  • All these five genetic conditions can be identified by newborn screening procedures due to elevated blood levels of Phe (with the sole exception of sepiapterin reductase deficiency). (thieme-connect.de)
  • Acetyl-CoA enters the Krebs cycle, also known as the citric acid or tricarboxylic (TCA) cycle, within the mitochondria. (oncohemakey.com)
  • The pathology of BH4 deficiencies explicates the types of oxidative stress that can also cause decreased BH4 caused by inherited hyperphenylalaninemia to mitochondrial diseases. (medscape.com)
  • Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). (wikipedia.org)
  • The enzyme can then further catalyze L-tyrosine to form L-DOPA. (wikipedia.org)
  • This initial reaction catalyzed by tyrosine hydroxylase has been shown to be the rate limiting step in the production of catecholamines. (wikipedia.org)
  • Similar to PKU, BH4 deficiencies negatively affect developmental function. (medscape.com)
  • The results of cDNA cloning, peptide mapping, and amino acid sequencing of PPAE revealed that PPAE is synthesized as prepro-PPAE with 441 amino acid residues and is activated from pro-PPAE by cleavage of a peptide bond between Lys152 and Ile153. (lookformedical.com)
  • [ 2 ] It was also shown that, in BH4 deficiency, dihydrofolate reductase (DHFR) plays a key role in regulating the ratio of BH4 to BH2 and eNOS coupling. (medscape.com)
  • Shen et al (2017) established that BH4 deficiency also occurs in Fabry disease and may contribute to its pathogenesis via oxidative stress due to reduced antioxidant capacity of cells and NOS uncoupling. (medscape.com)
  • A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. (bvsalud.org)
  • The products of enzymic oxidation of caffeic acid were analyzed and isolated by HPLC with diode array detection. (lookformedical.com)