Pyridoxine (Vitamin B6) Review

Pyridoxine (Vitamin B6)

Structure - has 6 vitamers which are interchangeable and comparably active:

SOURCES

DIGESTION, ABSORPTION, TRANSPORT, STORAGE

Absorption requires phophorylated vitamers by dephosphorylated.

• Alkaline phosphatase, zinc-dependent, performs this task at brush border

Free B6 is absorbed by passive diffusion.

Overall absorption 75%

Within enterocytes: no metabolism occurs

Released directly into the portal blood

In the liver:

• Taken up by passive diffusion
• Interconversion occurs between B6 forms requires RIBOFLAVIN:

• Intracellular [PLP] dependent on binding proteins
• With saturation, unbound PLP hydrolyzed to PL and released into blood

In systemic blood:

• PLP and PL major forms (75-90%)
• PLP bound to albumin with [ ] of 5-50ug/L
• Unphosphorylated vitamers are taken up by tissues

Storage:

• 40-185 mg in body
• Liver: 5-10%
• Muscles: 75-80%, bound  to glycogen synthetase

FUNCTIONS and MECHANISMS OF ACTION

PLP form functions as a coenzyme for 100+ reactions involving:

• Nutrient (amino acid) metabolism
• Neurotransmitter production
• Nucleic acid production
• Heme production
• Sphingomyelinas production
• Carnitine production
• Glucose production

As a coenzyme, B6 functions as a Schiff Base (product formed by an amino group and an aldehyde) to labilize all the bonds around the a-carbon of the amino acid.

Coenzymes

• Transanimation
• Involves the transfer of an amino group (NH2) form one amino acid to an a-ketoacid
• Synthesis of nonessential amino acids
• use of amino acid carbon skeletons for energy and glucose production (gluconeogenesis)
• Most common:
• AMINOTRANSFERASES:
• ASPARTIC AMINO TRANSFERASE (AST)
• ALANINE AMINO TRANSFERASE (ALT0
• 2 phases:

• Dehydration, elimination, deanimation
• Reactions in which amino group is removed from an amino acid and released as ammonia

• Decarboxylation
• Involves removal of the carboxy (COO-) group from an amino acid
• Production of neurotransmitters:
• GABA from glutamate
• Serotonin from 5HTP
• Histamine from Histidine
• Dopamine from dihydrophenylanine
• Taurine created during cysteine metabolism

• Transsulfhydation
• Pathway for cysteine formation from methionine
• Transelenation
• Antioxidant role involving selenium

• Cleavage
• Removal of the hydroxymethyl group from serine
• Production of nucleic acids
• Raceimization:
• Conversion between D and L amino acids
• Other synthetic reactions
• Heme synthesis involving aminolevulinic acid synthetase ~ deficiency = microcytic anemia
• Sphingolipid synthetase ~ myelin
• Fatty acid metabolism - desarturation of linoleic and linolinic acids
• Carnitine synthesis
• Niacin synthesis
• Nucleic acid production
• Glycogen degradation
• B6 required for glycogen phosphorylase activity
• 50% of the vitamins activity in body

Nonenzyme role: gene expression

METABOLISM AND EXCRETION

Urine as 4-pyridoxic acid

RDA

1.3 mg/d adults

DEFICIENCY

Noted in 2-3 weeks as seborrheic dermatitis

Seizures

Microcytic anemia

Homocysteinemia

RX: 2.5 to 25 mg daily for few weeks

Risk groups:

• Older
• Alcohol
• Systemic inflammation
• Medications:
• INH
• Penicillamine
• Steroids
• Seizure meds
• BCPs

TOXICITY

TUL > 200 mg /day ~ neuropathy

Avoid with Parkinsons on LDOPA

ASSESSMENT

Serum [PLP] <20 nmol/L

Urinary B6 and 4 pyridoxic acid

XAnthuremic acid excretion following tryptophan load

LFTs after B6 replacement

Erythrocyte transaminase