Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease

Kaler, Stephen G.; Goldstein, David S.; Holmes, Courtney; Salerno, Judith A.; Gahl, William A.

doi:10.1002/ana.410330206

Cited by 101 publications

(79 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The buildup of plasma L-DOPA probably results not only from the low enzymatic activity but also from increased tyrosine hydroxylation in sympathetic nerves. A high ratio of plasma L-DOPA/DHPG occurs in DBH deficiency (Biaggioni et al, 1990), Menkes disease (Kaler et al, 1993), and familial dysautonomia (Axelrod et al, 1998).…”

Section: Plasma Dopamentioning

confidence: 99%

“…In contrast, in DBH deficiency, failure to convert dopamine to norepinephrine leads to high plasma DOPAC levels and low DHPG levels (Goldstein et al, 1989). Menkes disease is an X-linked recessive disorder of a copper ATPase, and since DBH is a copper enzyme, patients with Menkes disease have decreased DBH activity, resulting in high plasma DOPAC/DHPG and high dopamine/norepinephrine ratios (Kaler et al, 1993). In deficiency of L-aromatic-amino acid decarboxylase, plasma levels of DOPA are high, whereas levels of DOPAC, DHPG, and dopamine sulfate are low, consistent with decreased conversion of DOPA to dopamine .…”

Section: Peripheral Dopaminergic Functionmentioning

confidence: 99%

See 1 more Smart Citation

Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans

Goldstein¹,

Eisenhofer²,

Kopin³

2003

J Pharmacol Exp Ther

Self Cite

383

312

View full text Add to dashboard Cite

Human plasma contains several catechols, including the catecholamines norepinephrine, epinephrine, and dopamine, their precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), and their deaminated metabolites, dihydroxyphenylglycol, the main neuronal metabolite of norepinephrine, and dihydroxyphenylacetic acid, a deaminated metabolite of dopamine. Products of metabolism of catechols include 3-methoxytyrosine (from L-DOPA), homovanillic acid and dopamine sulfate (from dopamine), normetanephrine, vanillylmandelic acid, and methoxyhydroxyphenylglycol (from norepinephrine), and metanephrine (from epinephrine). Plasma levels of catechols and their metabolites have related but distinct sources and therefore reflect different functions of catecholamine systems. This article provides an update about plasma levels of catechols and their metabolites and the relevance of those levels to some issues in human health and disease.Near the end of the 19th century, soon after the description of the profound cardiovascular effects of injected adrenal extract and the purification and identification of epinephrine as the vasoactive principal of the adrenal gland, researchers began to develop chemical means to assess activity of what came to be called the sympathoadrenomedullary system. The first chemical method for such measurement was colorimetric, based on the unusual susceptibility of epinephrine to oxidize, forming a brownish compound called "adrenochrome". Early attempts to measure circulating levels of epinephrine and related compounds chemically failed, mainly because the potency of epinephrine corresponds to very low normal concentrations in the bloodstream. Bioassays such as used by the great American physiologist, Walter B. Cannon were the first to detect successfully epinephrine release into the circulation. Cannon later developed and exploited a preparation based on the magnitude of the increase in heart rate in animals with denervated hearts; abolition of the increase by adrenalectomy confirmed the hormone's adrenal source. Subsequent chemical methods depended on fluorescence detection (after the trihydroxyindole reaction or ethylenediamine condensation) or radioenzymatic assays (after methylation with S-adenosylmethionine and catechol-Omethyltransferase). Ironically, current sensitive chemical methods using liquid chromatography with electrochemical detection depend on the same catechol oxidation as did the original colorimetric method.For almost the whole of the first half of the last century, epinephrine was the only catecholamine to receive attention. Cannon proposed-erroneously-that epinephrine was not only the main vasoactive hormone released by the adrenal gland but also the chemical messenger released from sympathetic nerves. This fit with his concept of a unitary sympathoadrenomedullary system, which would help maintain homeostasis (a word he coined) during emergencies but would not be necessary in day-to-day life. Fifty years after the discovery of epinephrine, norepinephrine, rather than epinephrine, was fi...

show abstract

Section: Plasma Dopamentioning

confidence: 99%

Section: Peripheral Dopaminergic Functionmentioning

confidence: 99%

Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans

Goldstein¹,

Eisenhofer²,

Kopin³

2003

J Pharmacol Exp Ther

Self Cite

383

312

View full text Add to dashboard Cite

show abstract

“…DBH is a copper enzyme, and patients with Menkes disease have neurochemical evidence for decreased DBH activity (46,47 …”

Section: Other Potential Usesmentioning

confidence: 99%

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

Self Cite

View full text Add to dashboard Cite

L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

show abstract

“…17 Because of decreased activity of dopamine-β-hydroxylase, the ratio of dihydroxyphenylacetic acid to dihydroxyphenylglycol is distinctively elevated in patients with Menkes disease. 18 From the known pathways of catecholamine synthesis and metabolism ( Fig. 1), one would also predict a high ratio of dopamine to norepinephrine.…”

mentioning

confidence: 99%