B6 Flashcards
Vitamin B6
pyridoxine
Pyridoxine properties
- water soluble
- unstable in UV light, heat, neutral/alkaline solutions
What are the 3 vitamers of pyridoxine?
- aldehyde = pyridoxal (PL)
- amine = pyridoxamine (PM)
- alcohol = pyridoxine (PN)
What vitamer is the active form of pyridoxine?
aldehyde = pyridoxal (PL)
* It is activated once it is phosphorylated to form pyridoxal phosphate (PLP) and is used as a co-factor in enzymes
interconversion of B6 vitamers
- The phosphorylated amine (pyridoxamine) and alcohol (pyridoxine) can be converted to pyridoxal phosphate via the enzyme PNP oxidase which is FMN (riboflavin) dependant.
- PL can be oxidized to pyridoxic acid, which is useless and can no longer be used as a vitamin
What is conversion of PNP oxidase dependant on?
PNP oxidase is FMN-dependent
Reactive group of PLP
- Carbonyl group in AA metabolism
- phosphate group in glycogen phosphorylase
Pyridoxine metabolic role
Serves as coenzyme for >100 enzymes
* primary role is amino acid metabolism
* Trp metabolism
* heme synthesis
* glycogen breakdown
What reactions does pyridoxine play a role in for amino acid metabolism?
- transamination
- decarboxylation = neurotransmitter synthesis
- transulfuration = homocysteine
- deamination
- phosphorylases & protein structure
How does PLP bind to enzymes
PLP binds to apoenzyme by a Schiff base
* The carbonyl group of the PLP has a double bond with nitrogen atom of the amino group of a lysine residue on the enzyme
What are transaminases and what are they important for?
catalyze transamination reactions where AA
transfer amino group to α-keto acids
* interconversion of AA
* catabolism of AA
* synthesis of non-essential AA
What is the role of PLP in transaminases?
PLP bound to the transaminase enzyme is what does all the action, so the amine group being donated from the AA binds first to the PLP at the active site and is then donated to the keto acid to form a new AA.
What are decarboxylases and what are they important for?
AA decarboxylation - remove carboxyl groups (CO2H)
* hormone & neurotransmitter synthesis
What is the role of PLP in decarboxylases?
Conversion requires vitamin B6 to make neurotransmitters
What is the transulfuration pathway and the role of PLP in Trans- & desulfuration?
The transsulfuration pathway plays a central role in sulfur metabolism and redox regulation in cells.
* trans-: Conversion of homocystein to cysteine requires PLP
* de-: conversion of cystein to pyruvate requires PLP
Role of pyridoxine in Trp metabolism
The last enzyme in the process of converting Trp to nicotinamide, kynureninase, is PLP dependant
* Very important for Niacin status
Role of PLP in heme synthesis
Involved in synthesis of heme via δ-aminolevulinate synthetase
* Rate limiting step in heme biosynthesis
dont memorize reaction
Role of PLP in glycogenolysis
More than 50% of B6 in the body is involved as a coenzyme of glycogen phosphorylase in muscle glycogenolysis
* In order to activate and breakdown glycogen to release glucose need VitB6 bound to this enzyme
Pyridoxine absorption and transport
Breakdown of ingested proteins via gastric acid releases PLP which is then dephosphorylated via phosphatases down to the vitaminer and then transported into enterocyte via carrier & passive diffusion. Some will be converted back to PLP via PL kinases, transaminase, PNP oxdase in enterocyte to be used but most will be transported to circulation and transported bound to albumin. Goes to liver first and be converted to active PLP where some PLP is converted to pyridoxic acid (useless) and is excreted and some PL/PLP goes to other tissue (via albumin bound). Enters tissue as PL, is converted to PLP where some binds to enzyme, some is excreted as the acid and some may leave as PL to go other places.
Pyridoxine storage
- main vstorage form = PLP
- PLP binds to proteins
- 80-90% body B6 stored in muscle; 10% in liver
- tissue protein capacity for binding PLP limits tissue accumulation of B6
Why is the bulk of B6 stored in the muscle?
Glycogen phosphorylase, and bulk of AA metabolism is contained in the muscle
Pyridoxine excretion
renal reabsorption
pyrdoxine food sources
Widely distributed
* richest sources: meats & unprocessed cereals
What are the forms of B6 in foods?
- animal tissue: PLP and PMP
- plant foods: PN
- supplements & fortified food: PN
How might B6 be lost from foods?
- heating
- milling/processing (75-90% loss)
- long storage (~1 year) → 25-50% loss
Bioavailability of B6
- Bioavailability in supplements is >90%
- Bioavailability in foods is ~75%
Why is B6 bioavailibilty in foods less?
The 75% bioavailability is based on removing it from whatever it is bound to
* highly variable
* most in food protein-bound
* PN-glycoside in plant tissues is poorly utilized
* PM can react with carbonyl group of reducing sugars & ascorbic acid rendering it inactive and is excreted
What are B6 requirements based on?
Requirements related to protein intake
B6 UL
UL = 100 mg/day
* high levels associated with sensory neuropathy
B6 RDAs
M/F - 1.3 mg/d
* increases in pregancy and lactation
Assessments for B6 status
- plasma PLP & urinary excretion of pyridoxic acid
- best: activity of dependant enzymes: RBC aspartate aminotransferase is a good functional assay
- Trp load = excretion of metabolites such as xanthurenic & kynurenic acids (build-up of intermedates in making niacin - indirect)
- Met load test: plasma & urinary Hcy & cystathionine
Prevalance of B6 deficiency
Rare because of:
* wide distribution
* possibly available from gut flora synthesis
How might B6 deficiency be present?
conditional deficiency not specific to B6
* defective intestinal absorption
* defective cellular & intercellular transport
* impaired oxidation or phosphorylation mechanisms
signs/ symptoms of B6 deficiency
- hematological: microcytic anemia (related to folate metabolism), hyper-Hcy
- nervous system: ataxia, depression, convulsions
- skin: dermatitis, lesions
Who is at risk for B6 deficiency?
- poor diet (Famine; but risk for all nutrients)
- drug-induced (Isoniazid; L-DOPA)
- Alcoholics
How might alcoholism result in B6 deficiency?
- ↓ B6 status independently
- acetaldehyde ↓ cellular PLP levels by displacing PLP from bind proteins rendering the enzymes inactive
Potential benefit of toxic dose of B6?
Possible (weak evidence) therapeutic effects on
* PMS
* depression
Problems with B6 toxicity
Acute toxicity low, but chronic dosing (>50 mg/d) may be dangerous
* highest safe dose not known
* some evidence for toxicity >500 mg/day (supplements)
* may result in peripheral sensory neuropathy
New research in B6
A chemical in flaxseed may bind to B6 and make it more deficient/ unavailable
* Conclusion: The current data from a rat model provide evidence that a vitamin B-6 antagonist now prevalent in the human food supply may pose challenges to individuals of moderate vitamin B-6 status.
