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