The INDIVIDUALIST

A Wiki about biochemical individuality

Biochemistry

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Description

Dopamine Beta Hydroxylase, or DBH, is the enzyme that converts dopamine to norepinephrine. Low DBH protein (detectable in the plasma and cerebrospinal fluid, CSF) leads to elevated ratios of dopamine to norepinephrine (hormones contribute to flight-flight endocrine responses), which explains associations between low DBH activity and neurobehavioral disorders like attention deficit hyperactivity disorder (ADHD) or psychotic symptoms, etc.

http://www.dadamo.com/wiki/dbh.jpg

Dopamine beta hydroxylase metabolism.

Norepinephrine (along with acetylcholine) is one of the two neurotransmitters in the peripheral nervous system. Norepinephrine is synthesized from dopamine by means of the DBH enzyme, with oxygen, copper and Vitamin C as co-factors. Dopamine is synthesized in the cytoplasm, but norepinephrine is synthesized in the neurotransmitter storage vesicles. Cells that use norepinephrine for formation of epinephrine use SAMe (S-AdenylMethionine) as a methyl group donor. Levels of epinephrine in the CNS are only about 10% of the levels of norepinephrine.

Discussion

Clinical features:
  • DBH levels are considered an index of sympathetic activity
  • Ptosis & delayed eye-opening
  • Hypotension, hypoglycemia, and hypothermia
  • Progressive postural hypotension with exertion
  • Nasal stuffiness
  • Reduced exercise tolerance

A single major quantitative trait locus (QTL), accounting for about half the heritability of DBH activity was initially mapped to chromosome 9q34 by linkage analysis in 1982 and again in 1988. Later studies identified the DBH gene, located within this region, as this QTL (1997-1998. The structural gene encoding DBH is ~23kb long and contains 12 exons.

A functional single polynucteotide polymorphism (SNP) (-1021 C/T), located within the promoter of the DBH gene, accounts for 35%–52% of the total variation in plasma DBH activity levels in three distinct populations. One SNP accounts for up to 50% of the variance seen in DBH plasma levels (again, populations studied unknown). This is a g/a substitution in exon 2 (exon2 *444g/a). These above two polymorphisms are thought to account for the majority of variance in plasma DBH activity .

Hypericin, the active ingredient in Saint John's Wort, may inhibit dopamine beta hydroxylase.

Links

OMIM 609312 - Dopamine Beta Hydroxylase

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