10.7: Vitamin B₆

Vitamin \(B_6\) is composed of three compounds: pyridoxine, pyridoxal, and pyridoxamine. Pyridoxine contains a methylhydroxyl group (\(\ce{-CH3OH}\)), pyridoxal an aldehyde (\(\ce{-CHO}\)), and pyridoxamine an aminomethyl group (\(\ce{-CH3NH2}\)), as shown below.

Figure \(\PageIndex{1}\): Structure of pyridoxine1

Figure \(\PageIndex{2}\): Structure of pyridoxal2

Figure \(\PageIndex{3}\): Structure of pyridoxamine3

Query \(\PageIndex{1}\)

All three forms can be activated by being phosphorylated. The phosphorylated forms can be interconverted to the active, or the cofactor form of vitamin \(B_6\), pyridoxal phosphate (\(\ce{PLP}\)). This active form has a phosphate group added in place of a hydroxyl group. The enzyme that catalyzes this reaction requires \(\ce{FMN}\) (riboflavin cofactor), as shown below.

Figure \(\PageIndex{4}\): Vitamin \(B_6\) activation1,4

In animal products, vitamin \(B_6\) is found in its cofactor forms, \(\ce{PLP}\) and pyridoxamine phosphate (\(\ce{PMP}\)). The latter cofactor is less common than \(\ce{PLP}\). In plants, vitamin \(B_6\) is primarily found as pyridoxine, with up to 75% being pyridoxine glucoside, which is believed to be the plant storage form6. Pyridoxine glucoside has a glucose added to pyridoxine as shown below.

Figure \(\PageIndex{5}\): Structure of pyridoxine glucoside5

Vitamin \(B_6\) is well absorbed from foods (~75%) through passive diffusion. \(\ce{PLP}\) and \(\ce{PMP}\) are dephosphorylated before uptake into the enterocyte. Some of the pyridoxamine glucoside is cleaved to form free pyridoxine, but some pyridoxine glucoside is absorbed intact. Pyridoxine glucoside absorption is lower (~50%) than pyridoxine alone. The primary circulating forms of vitamin \(B_6\) are pyridoxal and \(\ce{PMP}\). Vitamin \(B_6\) is primarily excreted in the urine, and like many other B vitamins, vitamin \(B_6\) is destroyed during cooking or heating6.

Query \(\PageIndex{2}\)

Vitamin \(B_6\) Functions

\(\ce{PLP}\) is a cofactor for over 100 different enzymes, most are involved in amino acid metabolism. In fact, without \(\ce{PLP}\), all amino acids would be essential because we would not be able to synthesize nonessential amino acids. Below are some of the functions of \(\ce{PLP}\) and \(\ce{PMP}\)7:

Figure \(\PageIndex{6}\): Transaminases require \(\ce{PLP}\) or \(\ce{PMP}\)8

Figure \(\PageIndex{7}\): Some deaminases require \(\ce{PLP}\)9

Figure \(\PageIndex{8}\): Glycogen phosphorylase (glycogenolysis) requires \(\ce{PLP}\)

\(\ce{PLP}\) is required for decarboxylase enzymes that are involved in the synthesis of the neurotransmitters GABA, serotonin, histamine, and dopamine. As an example, DOPA decarboxylase uses \(\ce{PLP}\) to convert L-DOPA to dopamine as shown below7.

Figure \(\PageIndex{9}\): DOPA decarboxylase uses \(\ce{PLP}\) to synthesize dopamine10

\(\ce{PLP}\) is also required by gamma-aminolevulinic acid (ALA) synthetase that is involved in heme synthesis, as shown below. Heme will be discussed in more detail in the iron section.

Figure \(\PageIndex{10}\): ALA synthetase uses \(\ce{PLP}\) in the heme synthesis pathway11

\(\ce{PLP}\) is also used in one of the multiple reactions that occurs between kynurenine and niacin in its synthesis from tryptophan.

Figure \(\PageIndex{11}\): \(\ce{PLP}\) is required for niacin synthesis from tryptophan12

In addition, \(\ce{PLP}\) is also involved in:

• Carnitine Synthesis
• 1-Carbon Metabolism

Query \(\PageIndex{3}\)

Vitamin \(B_6\) Deficiency & Toxicity

Vitamin \(B_6\) deficiency is rare, but symptoms include:

• Skin or scalp ailments (seborrheic dermatitis)
• Microcytic hypochromic anemia (small cells, low color)
• Convulsions
• Depression
• Confusion

Given what we know about the functions of vitamin \(B_6\) most of these symptoms make sense. The microcytic hypochromic anemia is a result of decreased heme synthesis. The neurological symptoms are due to the decreased production of neurotransmitters13.

Vitamin \(B_6\), unlike many of the B vitamins, can produce toxicity. High doses of vitamin \(B_6\), taken for an extended period of time, can lead to neurological damage13. There are some potential uses of vitamin \(B_6\) supplementation that are important to be done with consultation with a physician. The levels at which vitamin \(B_6\) is supplemented for these uses is usually nearing its UL, which is why care should be taken in how this is done.

Carpal tunnel syndrome is a condition that some people take a vitamin \(B_6\) supplement for. The following video does a nice job of explaining and showing how this condition occurs.

Video \(\PageIndex{1}\): Carpal Tunnel Syndrome. https://www.youtube.com/watch?v=rewDQgqU5Hg

While the evidence is not conclusive, it appears that vitamin \(B_6\) supplementation may be beneficial to those suffering from carpal tunnel syndrome and may be tried alone, or in combination with other complementary treatments, before surgery is undertaken14,15.

Morning sickness (hyperemesis gravidarum) that occurs early in pregnancy is another condition where vitamin \(B_6\) supplementation is utilized. The evidence again is not clear on whether it is beneficial16,17, but The American College of Obstetricians and Gynecologists suggests that vitamin B6 may be tried first to treat nausea and vomiting during pregnancy18. In 2013, the FDA approved doxylamine-pyridoxine (Diclegis) for use in pregnancy19. It is not known exactly what causes morning sickness, but it is believed that lower circulating vitamin B6 levels are associated with increased morning sickness severity20.

The last condition that vitamin B6 is commonly supplemented for is premenstrual syndrome (PMS). A systematic literature review found that it is inconclusive whether vitamin \(B_6\) supplementation is beneficial in managing PMS21.

Query \(\PageIndex{4}\)

References

1. en.Wikipedia.org/wiki/File:Py..._structure.svg
2. en.Wikipedia.org/wiki/File:Pyridoxal.png
3. en.Wikipedia.org/wiki/File:Pyridoxamine.png
4. en.Wikipedia.org/wiki/Pyrido...-phosphate.svg
5. http://pubchem.ncbi.nlm.nih.gov/summ...188&loc=ec_rcs
6. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. (2006) Modern nutrition in health and disease. Baltimore, MD: Lippincott Williams & Wilkins.
7. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
8. en.Wikipedia.org/wiki/File:Transaminierung.svg
9. en.Wikipedia.org/wiki/File:De...ierungCtoU.png
10. en.Wikipedia.org/wiki/File:Ca...osynthesis.svg
11. en.Wikipedia.org/wiki/File:Heme_synthesis.png
12. commons.wikimedia.org/wiki/F...synthesis2.png
13. Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.
14. Ryan-Harshman M, Aldoori W. (2007) Carpal tunnel syndrome and vitamin B6. Canadian Family Physician 53(7): 1161-1162.
15. Aufiero E, Stitik T, Foye P, Chen B. (2004) Pyridoxine hydrochloride treatment of carpal tunnel syndrome: A review. Nutr Rev 62(3): 96-104.
16. Koren G, Maltepe C. (2006) Preventing recurrence of severe morning sickness. Canadian Family Physician 52(12): 1545-1546.
17. Tan P, Yow C, Omar S. (2009) A placebo-controlled trial of oral pyridoxine in hyperemesis gravidarum. Gynecol Obstet Invest 67(3): 151-157.
18. www.acog.org/Patients/FAQs/Mo...g-of-Pregnancy
19. Slaughter SR, Hearns-Stokes R, van der Vlugt T, Joffe HV. (2014) FDA approval of doxylamine-pyridoxine therapy for use in pregnancy. N Engl J Med. 370: 1081-1083.
20. Wibowo N, Purwosunu Y, Sekizawa A, Farina A, Tambunan V, Bardosono S. (2012) Vitamin B6 supplementation in pregnant women with nausea and vomiting. 116: 206-210.
21. Whelan A, Jurgens T, Naylor H. (2009) Herbs, vitamins and minerals in the treatment of premenstrual syndrome: A systematic review. The Canadian Journal of Clinical Pharmacology 16(3): e407-e429.