The Organic Acids Test measures levels of HVA (homovanillic acid) and VMA (vanillylmandelic acid), the metabolites of the neurotransmitters, dopamine and epinephrine/norepinephrine. It also measures the ratio of the two metabolites.
Homovanillic acid (HVA) is a major catecholamine metabolite that is produced by a consecutive action of monoamine oxidase and catechol-Omethyltransferase on dopamine. HVA is associated with dopamine levels in the brain. Dopamine (3,4-dihydroxyphenethylamine) is a major excitatory neurotransmitter that functions both as a hormone and a neurotransmitter and plays several important roles in the brain and body. It is synthesized in the brain and kidneys. In the brain, dopamine functions as a neurotransmitter that acts on several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior.
Vanillylmandelic acid (VMA) is an end stage metabolite of is an end-stage metabolite of the catecholamines dopamine, epinephrine, and norepinephrine formed via the actions of monoamine oxidase, catechol-O-methyl transferase (COMT), and aldehyde dehydrogenase. VMA is found in the urine, along with other catecholamine metabolites, including homovanillic acid (HVA), metanephrine, and normetanephrine.
Elevated HVA and decreased VMA may be caused by Clostridia infection or lead toxicity.
An elevated ratio is often the result of decreased conversion of dopamine to norepinephrine by the enzyme, dopamine beta-hydroxylase. This inhibition is commonly caused by Clostridia by-products, including HPHPA, 4-cresol, and 4-hydroxyphenylacetic acid, which are also measured in the OAT.
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The HVA/VMA ratio reflects the balance between dopamine and norepinephrine/ epinephrine production by catecholamine producing neurons in the central nervous system, sympathetic nervous system, and adrenal gland.
- A common reason for an elevation of the HVA/VMA ratio is a decreased conversion of dopamine to norepinephrine. The enzyme responsible for this conversion, dopamine beta-hydroxylase (DBH), is copper and vitamin C dependent so an elevated ratio could be due to deficiencies of these cofactors .
- Another common reasons for this elevated ratio is inhibition of this enzyme by Clostridia byproducts including HPHPA, 4-cresol, or 4-hydroxyphenylacetic acid.
- Other causes of an increased ratio include inhibition of DBH by the mold metabolite fusaric acid, pharmaceuticals such as disulfiram, or food additives like aspartame.
- Another cause for an elevated ratio is a genetic variation (single nucleotide polymorphism or SNP) of the DBH enzyme. Alternatively, the activity of the DBH enzyme can be measured on blood serum.
- High ratios are common in a large number of neuropsychiatric diseases regardless of the reason for DBH deficiency.
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2-Hydroxyhippuric acid, 2-Hydroxyisocaproic acid, 3-Methyl-2-oxovaleric acid, Arabinose, Ascorbic acid (Vitamin C), Citric acid, Furancarbonylglycine, GABA, Glyceric acid, HVA/DOPAC, HVA/VMA Ratio, Lactic acid, Methylmalonic acid (Vitamin B12), Norepinephrine/Epinephrine, Quinolinic acid/5-HIAA, Quinolinic acid/5-HIAA Ratio, Suberic acid