B6 Carbidopa Aromatic Amino Acid Decarboxylase

The effects of carbidopa on vitamin B6 in the human body (part 3 of 4)

Vitamin B6 is a water-soluble vitamin that was first isolated in the 1930s. The term vitamin B6 refers to six common forms, namely pyridoxal, pyridoxine (pyridoxal), pyridoxamine, and their phosphorylated forms.¹ However, outcomes do not differ when giving each of the six forms. Therefore, the most significant problem with vitamin B6 administration is simple; not giving enough.

Figure 1

PLP is a common acronym used in scientific writings for the vitamin B6 form known as pyridoxal-5-phosphate. For activation of the vitamin B6-dependent enzyme, a vitamin B6 molecule binds to the inactive enzyme (the apoenzyme); the result is an active enzyme where the vitamin B6 molecule becomes the active site on the enzyme. The active site is where the precursor temporarily binds while the enzyme converts it to the metabolite such as dopamine, serotonin, or histamine.

Figure 2^2,3

Figure 3: L-dopa is metabolized to dopamine by the aromatic amino acid decarboxylase enzyme (AADC).⁴ Therefore, when significant depletion of vitamin B6 by carbidopa occurs, dopamine synthesis decreases (becomes depleted), and symptoms dependent on dopamine concentrations increase. This increase in symptoms may be confused with the worsening of a disease associated with low dopamine concentrations when the real problem is drug-induced (carbidopa) dopamine depletion symptoms secondary to depletion of the activated AADC enzyme.

The vitamin B6-dependent enzyme aromatic amino acid decarboxylase catalyzes the metabolism of 5-HTP to serotonin, L-dopa to dopamine, and histidine to histamine. Therefore, depleting vitamin B6 by carbidopa may cause inadequate serotonin, dopamine, and histamine inside and outside the brain.

Figure 4

Vitamin B6 freely crosses the blood-brain barrier.⁵ Therefore, depleting peripheral (outside the brain) vitamin B6 by carbidopa leads to depletion of inside the brain’s vitamin B6 levels. So what does this mean? First, symptoms dependent on dopamine, serotonin, or histamine concentrations can worsen as vitamin B6 concentrations throughout the body, including the brain, are depleted by carbidopa.

Figure 5

The mechanism of action for carbidopa and benserazide induces irreversible binding to and permanent deactivation of PLP (vitamin B6) and PLP-dependent enzyme molecules, potentially inducing a negative impact on over 300 enzymes and proteins. Without the induction of PLP depletion and deficiency, the clini¬cal effects of carbidopa and benserazide are not observed. It is a documented fact that these drugs may induce system-wide B6 depletion, representing a B6 nutritional collapse that may be reversed with vitamin B6 administration. But if B6 is administered while taking carbidopa the irreversible binding between B6 and carbidopa will lead to a decrease in available carbidopa.

¹ Vitamin B6 | Linus Pauling Institute | Oregon State University last accessed December 10, 2021
² UniProt [webpage on the Internet]. UniProt. UniProt Consortium; 2014. Available from: https://www.uniprot.org/uniprot/?query=pyridoxal+AND+organism%3A%22Homo+sapiens+%5B9606%5D%22&sort=score Last accessed December 10, 2021
³ Paiardini A, Contestabile R, Buckle AM, Cellini B. PLP-dependent enzymes. Biomed Res Int. 2014;2014:856076. Last accessed December 10, 2021
⁴ Enzyme 4.1.1.28 https://www.genome.jp/dbget-bin/www_bget?ec:4.1.1.28 last accessed December 10, 2021
⁵ Centers for Disease Control and Prevention [webpage on the Internet]. Health data interactive. Atlanta, GA: Centers for Disease Control and Prevention; 2014. Available from: http://www.cdc.gov/nchs/hdi.htm. last accessed December 10, 2021