DOPAC
Dopac (aka 3,4-Dihydroxyphenylacetic acid) is a metabolite of the neurotransmitter dopamine. Dopamine serves as the reward and pleasure center in the brain. DOPAC and HVA (Homovanillic Acid) are dopamine metabolites.
DOPAC levels, when viewed in conjunction with dopamine levels, may provide insight into how the body processes neurotransmitters.
Some of the enzymes that degrade dopamine are only found in specific regions of the body. As such some dopamine metabolites are only produced in specific tissues. Understanding how and where these enzymes function can provide valuable insight into how dopamine is functioning in specific regions of the body. In order to understand these functions, one must first realize Monoamine oxidase (MAO) is an enzyme present within the cytoplasm of neurons that breaks down dopamine to DOPAL. DOPAL, in turn, is very rapidly converted to DOPAC by a second cytoplasmic enzyme aldehyde dehydrogenase (AD). Because both of these enzymes are primarily found inside neurons, DOPAC levels are dependent on the amount of cytoplasmic dopamine. Combined measurements of DOPAC and dopamine have been used to assess the activity of dopaminergic neurons. This combination provides additional information than either parameter alone because a large portion of DOPAC is formed from dopamine without ever being released to the synaptic cleft. This suggests that DOPAC may be more closely related to the presynaptic dopamine levels while dopamine and similarly HVA levels, another important metabolite of dopamine that is formed outside of the neuron via the actions of catechols-O-methyltransferase (COMT), is related to the rate of neuron signaling. Said another way, extracellular DOPAC is related to the amount of dopamine made and stored in the presynaptic neuron while extracellular dopamine levels are related to the rate of dopamine released via the depolarization of dopamine neurons.
References:
- https://www.researchgate.net/figure/The-metabolism-of-dopamine-into-DOPAC-3-4-dihydroxyphenylacetic-acid-and-3-MT_fig8_237098396
- http://www.hmdb.ca/metabolites/HMDB0001336
- https://www.acam.org/blogpost/1092863/229831/Advances-in-Neurotransmitter-Testing-The-Intermediaries-of-the-Neuro-biogenic-Amines
- https://www.ncbi.nlm.nih.gov/pubmed/19945170
- https://www.ncbi.nlm.nih.gov/pubmed/23892640
- https://www.ncbi.nlm.nih.gov/pubmed/1583475
- https://www.ncbi.nlm.nih.gov/pubmed/21806773
- https://www.ncbi.nlm.nih.gov/pubmed/1718014
- https://www.ncbi.nlm.nih.gov/pubmed/22200523
- https://www.ncbi.nlm.nih.gov/pubmed/15082158
- https://www.ncbi.nlm.nih.gov/pubmed/23850225
- https://www.ncbi.nlm.nih.gov/pubmed/21806773
What does it mean if your DOPAC result is too high?
- High dopamine is reported in people with high in anxiety, stress, PTSD, and mercury toxicity.
- An elevated DOPAC level can indicate increased dopamine breakdown, leading to increased levels of free radicals. This oxidative stress can affect neurotransmitter pathways. The neurotransmitter pathways, in turn, can also impact the total oxidative stress in a patient.
- Research shows that DOPAC is elevated in patients with anorexia nervosa (Van Binsbergen et al., 1991).
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- Dopamine Beta-Hydroxylase inhibition
- Polymorphism
- Clostridia toxin inhibition
- Vitamin C and/or copper deficiency. Vit C and Copper are co-factors of DBH and are needed for DBH to function properly.
--> In the above cases if Dopamine cannot be properly converted to Norepinephrine via the Dopamine Beta-Hydroxylase, both DOPAC and HVA (Homovanillic Acid) increase.
- Deficiency of SAMe:
- SAMe 200mg to 400mg BID
- Catechol-O-methyltransferase (COMT) polymorphism. A heterozygous or homozygous mutation in COMT can affect the function of COMT, which leads to a rise in DOPAC.
- Magnesium deficiency
- Increased L-Tyrosine and/or Phenylalanine consumption.
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What does it mean if your DOPAC result is too low?
Dopamine is low in Alzheimer’s disease, anorexia nervosa, fibromyalgia, periodic limb movement disorder, sleep disturbances.
DOPAC levels may be low simply if dopamine levels are low. DOPAC is the primary metabolite of dopamine formed by MAO activity. Alternatively low levels of DOPAC may be associated with medications such as adrenergic antagonists, monoamine or norepinephrine reuptake inhibitors. Low DOPAC levels may also indicate low activity of MAO-A. Vitamins B2, B3, B6, and iron are required for optimal dopamine metabolism. Although a low level of urinary DOPAC is absolutely not diagnostic, low DOPAC levels in cerebral spinal fluid have been associated with Parkinson’s disease.
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- Decreased intake or absorption of L-Tyrosine and/or Phenylalanine (=precurosors to dopamine).
- Vitamin B6 deficiency.
- Polymorphism of MAO enzyme.
- MAO inhibitors, i.e. durgs, certain summplements like turmeric and kava.
- Decreased BH4 (=tetrahydrobiopterin). BH4 is a cofactor in various places in the Phenylalanine and Tyrosine metabolism.
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