Catecholamine Biochemical Genetics

Weinshilboum, Richard M.

doi:10.1007/978-3-642-73551-6_10

Cited by 5 publications

(5 citation statements)

References 87 publications

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“…The results of pedigree and segregation analysis of data from families selected because they included a proband with ''low'' activity were compatible with monogenic inheritance of the level of human RBC COMT activity (Weinshilboum & Raymond 1977a). These and subsequent studies indicated that subjects homozygous for an allele for low activity, COMTL, had low levels ofenzyme activity (<8 units/ml), and subjects homozygous for an alternative allele, COMTH, had high RBC COMT activity (Weinshilboum & Raymond 1977a, Weinshilboum 1978a, Weinshilboum 1979b, Spielman & Weinshilboum 1979, Gershon et al 1980.…”

Section: Rbc Comt Blochernical Geneticsmentioning

confidence: 71%

“…The gene frequencies of the two alleles were approximately equal in the white population studied initially, although preliminary data indicate that the gene frequencies of COMTL and COMTH may vary widely among different racial groups (Reilly & Rivera-Calimlim 1979). The alleles for low and high enzyme activity were designated COMTL and COMTH to conform to the recommendations of the Third International Workshop on Human Gene Mapping (Committee on Nomenclature, 1976, Scanlon et al 1979, Weinshilboum 1979b. The monogenic inheritance of the level of RBC COMT activity raised the possibility that the biochemical properties of the enzyme might differ in subjects with different genotypes for the locus COMT.…”

Section: Rbc Comt Blochernical Geneticsmentioning

confidence: 99%

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Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Weinshilboum

Dunnette

1981

Clinical Genetics

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The levels of activity of human erythrocyte (RBC) catechol‐O‐methyl‐transferase (COMT) and human plasma dopamine‐β‐hydroxylase (DBH) are inherited in a monogenic fashion. The COMT in erythrocytes of subjects homozygous for the allele for low basal enzyme activity, COMTL, is more thermolabile than that in the erythrocytes of subjects with genetically high basal enzyme activity. This observation suggests that the locus COMT may represent the structural gene for COMT in man. Wide individual variations in the thermal stability of human plasma DBH also occur. There is a significant familial aggregation of the trait of thermolabile plasma DBH. Although subjects with thermolabile plasma DBH have average basal plasma DBH activity only about 55% of that of subjects with thermostable enzyme, the trait of thermolability does not cosegregate with DBHLL, the allele for very low basal plasma DBH activity. Studies of thermal stability may help to increase our understanding of the biochemical basis of the genetic regulation of catecholamine enzymes in man.

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Section: Rbc Comt Blochernical Geneticsmentioning

confidence: 71%

Section: Rbc Comt Blochernical Geneticsmentioning

confidence: 99%

Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Weinshilboum

Dunnette

1981

Clinical Genetics

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“…Data from segregation analysis provided evidence for the control of COMT activity by a major autosomal locus with two alleles (9). Variations in COMT activity are found in patients with major depression, recurrent and bipolar disorders (10), as well as in children with Down syndrome (11).…”

mentioning

confidence: 99%

Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form.

Bertocci

Miggiano

Prada

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

170

105

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A cDNA clone for human catechol-Omethyltransferase (hCOMT; S-adenosyl-L-methionine:catechol O-methyltransferase; EC 2.1.1.6) was isolated from a human hepatoma cell line (Hep G2) cDNA library by hybridization screening with a porcine cDNA probe. The cDNA clone was sequenced and found to have an insert of 1226 nucleotides. The deduced primary structure of hCOMT is composed of 271 amino acid residues with the predicted molecular mass of 30 kDa. At its N terminus it has a hydrophobic segment of 21 amino acid residues that may be responsible for insertion of hCOMT into the endoplasmic reticulum membrane. The primary structure of hCOMT exhibits high homology to the porcine partial cDNA sequence (93%). The deduced amino acid sequence contains two tryptic peptide sequences ( Catechol-O-methyltransferase (COMT; S-adenosyl-L-methionine; catechol O-methyltransferase; EC 2.1.1.6) is an enzyme that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the m-hydroxy group of catecholamine neurotransmitters (dopamine, noradrenaline, adrenaline), their metabolites, and L-dopa, thereby inactivating them. The enzyme has a broad substrate specificity accepting as substrate also catechol steroids, a-methyldopa, and apomorphine (1). It is widely distributed in various cerebral and extracerebral tissues of all mammalian species (2), including erythrocytes (3). The occurrence of at least two distinct isoforms of COMT has been demonstrated, of which one is soluble (S-COMT) and the other membrane-bound

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“…These facts have dampened enthusiasm for the use of serum DBH as a measure of acute alterations in adrenergic activity in humans. 19 Biochemical genetic studies of the 1970s and early 1980s using these assays documented polymorphism in DBH in apparently healthy individuals. Serum DBH enzymatic activity and immunoreactive protein increase from low levels in young children to high levels in most adults, but levels of both remain low in a minority.…”

mentioning

confidence: 99%

“…19 These individuals have much higher amounts of immunoreactive material than enzymatic DBH activity. This disparity may reflect changes in the active site and could indicate subclinical impaired function.…”

mentioning

confidence: 99%

Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation.

et al. 1991

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Dopamine /3-hydroxyIase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one. (Hypertension 1991;18:l-8)

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Catecholamine Biochemical Genetics

Cited by 5 publications

References 87 publications

Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Thermal stability and the biochemical genetics of erythrocyte catechol‐O‐methyltransferase and plasma dopamine‐β‐hydroxylase

Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form.

Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation.

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