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Clinical biochemistry - Assignment Example

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Clinical Biochemistry Assignment Other name (s) Course Clinical Biochemistry Assignment Enzymes COMT (Catechol-O-methyltransferase) COMT (Catechol-O-methyltransferase) is an important enzyme that acts as a catalyst in the transfer of methyl group from S-adenosylmethione to catecholamines including epineprhrine, neurotrsnmitters, dopamine and nonepineprhrine (BRENDA 2)…
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Clinical Biochemistry Assignment Other (s) Clinical Biochemistry Assignment Enzymes COMT (Catechol-O-methyltransferase) COMT (Catechol-O-methyltransferase) is an important enzyme that acts as a catalyst in the transfer of methyl group from S-adenosylmethione to catecholamines including epineprhrine, neurotrsnmitters, dopamine and nonepineprhrine (BRENDA 2). The process of O-methylation normally occurs in one of the degenerative pathways of catecholamine transmitters. In this regard, the pathways include dopamine degradation and betaxanthin biosynthesis. Encoded by COMT gene, Catechol-O-methyltransferase also plays a critical role in the metabolism of many catechol drugs used in the treatment of hypertension, Parkinson’s disease and asthma. The main co-factor is magnesium ion. On the other hand, substrates of COMT generally include any compound with a catechol structure such as catechol-containing flavanoids and catechoestrogens. Other substrates for the enzyme include epicatechin + S-adenosyl-L-methionine, epigallocatechin-3-O-gallate + S-adenosyl-L-methionine and (R)-1,2-dihydroxy-4-[2-(methylamino)butyl]benzene + S-adenosyl-L-methionine. A patient with mutations(single nucleotide polymorphism that eliminates or reduces the function of Catechol-O-methyltransferase is likely to suffer from a wide range of difficulties including panic disorder, paranoid schizophrenia among other related conditions due to the impaired regulation of catecholamines (Golan 210).   MAO (Monoamine oxidase) Monoamine oxidase is a group of enzymes that functions by catalyzing the oxidative deamination of monomines. In humans, the enzymes occur in two major types namely, MAO-A and MAO-B both of which are commonly found in the astroglia and neurons as well as outside the central nervous system. They are normally classified as flavoproteins due to the fact that they contain covalently bonded cofactor FAD. MAO itself is considered to be a substrate for most monoamine oxidase drugs (Edmondson 86). The common substrates for the enzyme include monoamines in the ingested food (MAO-A), monoaminergic neurotransmitters, tyramine and dopamine. Specific substrates for MAO-A include Melatonin, adrenaline, Serotonin and noradrenaline while MAO-B usually breaks down benylamine and Phenethylamine. A patient with dysfunctional MAO due to mutations is likely to suffer from a wide range of neurological and psychiatric disorders such as attention deficit disorder, schizophrenia, migraines, substance abuse and irregular sexual maturation. BHMT (Betaine homocysteine methyltransferase) This is an important enzyme belonging to the family transferases that is involved in homocysteine metabolism particularly by acting as a catalyst in the conversion of homocysteine and betaine to methionine and dimethylglycine respectively. BHMT is mostly expressed in the kidney and the liver and the cofactor is zinc ion in humans. On the other hand, the pathways include glycine betaine degradation, Amine and polyamine degradation, sarcosine from betaine, metabolic pathways, L-methethionine biosynthesis via de novo pathway as well as step ?Amino acid biosynthesis. The natural substrates for humans include betaine, L-homocysteine and S-methyl-L-methionine. Any anomaly in the Betaine homocysteine methyltransferase particularly due to mutation may result in homocysteine metabolism thereby leading to disorders such as vascular disease as well as a number of neural tube birth defects like spina bifida. CBS (Cystathionine ?-Synthase) Cystathionine ?-Synthase normally functions as a catalyst in the first step of the transssulfuration pathway between homocysteine and cystathione (Jhee 820). The co-factors involved in the enzymatic reaction include pyridoxical 5-phosphate (PLP), heme and S-adenosyl-L-methionine. The enzyme belongs to family of hydro-lyses that particularly works by cleaving carbon-hydrogen bonds. Human CBS plays a critical role in the biosynthetic pathway of cysteine particularly by providing an important regulatory control point for AdoMet. The main substrates for the enzyme include L-cysteine + 2-mercaptoethanol, L-Cysteine + DL-homocysteine nucleic acids and neurotransmitters. The overexpression or underexpression of CBS due to mutation and single nucleotide polymorphisms often result in a wide range of conditions in humans. For example, Down syndrome is normally characterized by a low level of homocysteine in an individual’s blood as well as an over-expression of CBS. On the other hand, CBS deficiency may result in hyperhomocysteinemia characterized by cardiovascular complications that usually lead to early arterial disease.  SHMT (Serine hydroxymethyltransfase) The enzyme Serine hydroxymethyltransfase (SHMT) plays a critical role as a catalyst in the cellular one-carbon pathways particularly by catalyzing the reversible conversions of glycine and L-serine. This reaction is primarily attributed to the production of the largest part of the one carbon units for the human cells. The co-factors of the enzyme in humans include pyridoxal 5’-phosphate, Zinc and tetrahydrofolate (BRENDA 3). On the other hand, the main pathways are folate transformation, cyanoamino acid metabolism. glucine betaine degradation, methane metabolism and Glycine metabolism. Lastly, the substrates of the enzyme include alpha-methylserine + tetrahydrofolate and 5,10-methenyl-tetrahydropteroyl. Works Cited BRENDA. “Enzymes.” Brenda-enzymes.org.Web. 22. Dec. 2013. Edmondson, Donald, E. “Structure and mechanism of monoamine oxidase.” Curr. Med. Chem. 11.15(2004): 83-93. Print. Golan, David E. and Armen H. Tashjian. Principles of pharmacology (3rd ed.). Philadelphia: Wolters Kluwer Health. Print. Jhee, Kruger W. “The role of cystathionine beta-synthase in homocysteine metabolism”. Antioxidants & Redox Signaling 7.5(2005): 813-822.Print. Sesardic, Neven. Making sense of heritability. Cambridge, UK: Cambridge University Press, 2005. Print. Read More
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