Vitamin B6

Functions
Sources
Metabolism
Requirements
Deficiency
Toxicity

I.  Functions

1. Transamination. PLP and PMP can serve as coenzyme for aminotransferases
   1. Glutamate oxaloacetate transaminase (also called aspartic amino transaminase)
   2. Glutamate pyruvate transaminase (also called alanine amino transaminase)
2. Decarboxylation
   1. Formation of g-aminobutyric acid (GABA) from glutamate
   2. Production of serotonin from 5-hydroxytryptophan
3. Transsulfhydration and Desulfhydration
   1. Synthesis of cysteine from methionine
      1. Both cystathionine synthase and cystathionine lyase require PLP
      2. Cysteine undergoes desulfhydration followed by transamination to generate pyruvate
4. Cleavage
   1. PLP is required for removal of the hydroxymethyl group from serine
   2. PLP is the coenzyme for a transferase that transfers the hydroxymethyl group of serine to tetrahydrofolate so that glycine is formed
5. Racemization
   1. PLP is required by racemases that catalyze interconversion of D-and L- amino acids
   2. More prevalent in bacteria but occurs in humans
6. Synthesis
   1. Synthesis of heme
   2. Niacin (NAD) synthesis from tryptophan requires a PLP-dependent reaction
   3. Histamine from the amino acid histidine
   4. Carnitine
   5. Taurine and dopamine which have neuromodulatory functions
7. Glycogen catabolism
   1. Vitamin B₆ is required for glycogen phosphorylase which catabolizes glycogen by forming glucose-l-PO₄
8. Steroid hormone action
   1. PLP reacts with lysine residues in steroid hormone receptor proteins to interfere with hormone binding
   2. These receptor proteins mediate nuclear uptake of steroid hormone
   3. For example, diminishing action of glucocorticoid hormones can in turn influence metabolism of protein, carbohydrate and lipid

II.  Sources

1. Good sources: liver, muscle meats, fish, yeast, whole grain cereals, bran from cereal grains
2. Fair sources: milk, eggs, green leafy vegetables

III.   Metabolism

1. Absorption
   1. Phosphorylated forms must first be dephosphorylated by alkaline phosphatase or other intestinal phytases
   2. Absorption of PL, PN, and PM occurs primarily in the jejunum by passive diffusion
   3. Within intestinal cell, PN and PL are converted to PNP and PLP, respectively. PNP may be converted to PLP
   4. PLP and PL and some PM are bound to albumin for transport in plasma
   5. In the liver, unphosphorylated forms are phosphorylated and PN and PMP are generally converted to PLP
   6. In the tissues, only PL is taken up and PLP must be hydrolyzed before uptake
   7. Within the cells, PL is phosphorylated by pyridoxine kinase
   8. PNP/PMP oxidase in tissues convert PNP and PMP into PLP, the coenzyme form of the vitamin.
      1. PNP/PMP oxidase is a flavin mononucleotide (FMN)-dependent enzyme
      2. Normal vitamin B₆ metabolism is closely interrelated with riboflavin
2. Excretion
   1. Intracellular level of PLP is believed to be controlled by enzymatic hydrolysis
   2. Another possibility for regulating PLP is inhibition of PNP/PMP oxidase
   3. Pyridoxic acid is the major excretory product in urine

IV.  Requirements

1. Requirement for vitamin B6 is related to level of protein intake. An intake of 16 mg of vitamin B₆ per 1 g of protein is considered adequate for adult humans under normal conditions
2. Recommended allowances
   1. Human....................2-2.5 mg/day
   2. Pig...........................1.1-1.5 mg/kg BW
   3. Chick and turkey.....3 mg/kg

V.  Deficiency

1. Symptoms are usually associated with deficiency of other B vitamins
2. Factors reducing pyridoxal utilization
   1. Oral contraceptives
   2. Antagonists
   3. 4 deoxypyridoxine is phosphorylated and competes for binding to PLP-dependent enzymes but cannot function as a coenzyme
   4. Penicillamine used to remove excess copper in Wilson's disease
   5. Isoniazid, a tuberculostatic drug
3. Deficiency symptoms
   1. Human
      1. Skin changes: dermatitis, glossitis
      2. Hematologic changes: decreases in lymphocytes, anemia
      3. Nervousness, electroencephalographic abnormalities, neurotic
      4. tendencies, depression, convolusive seizures
   2. Pigs
      1. Growth failure, anorexia
      2. Rough hair coat
      3. Microcytic hypochromic anemia
      4. Ataxia, demyelinizatoin of peripheral nerves

VI.  Toxicity

1. Acute toxicity is very low
2. Chronic use of 2-6 g/day (1000-2700 times the RDA) in humans results in nervous system disorders similar to those seen with a deficiency

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