B6

Question 1

Vitamin B6

Answer 1

pyridoxine

Question 2

Pyridoxine properties

Answer 2

• water soluble
• unstable in UV light, heat, neutral/alkaline solutions

Question 3

What are the 3 vitamers of pyridoxine?

Answer 3

• aldehyde = pyridoxal (PL)
• amine = pyridoxamine (PM)
• alcohol = pyridoxine (PN)

Question 4

What vitamer is the active form of pyridoxine?

Answer 4

aldehyde = pyridoxal (PL)
* It is activated once it is phosphorylated to form pyridoxal phosphate (PLP) and is used as a co-factor in enzymes

Question 5

interconversion of B6 vitamers

Answer 5

• 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

Question 6

What is conversion of PNP oxidase dependant on?

Answer 6

PNP oxidase is FMN-dependent

Question 7

Reactive group of PLP

Answer 7

• Carbonyl group in AA metabolism
• phosphate group in glycogen phosphorylase

Question 8

Pyridoxine metabolic role

Answer 8

Serves as coenzyme for >100 enzymes
* primary role is amino acid metabolism
* Trp metabolism
* heme synthesis
* glycogen breakdown

Question 9

What reactions does pyridoxine play a role in for amino acid metabolism?

Answer 9

• transamination
• decarboxylation = neurotransmitter synthesis
• transulfuration = homocysteine
• deamination
• phosphorylases & protein structure

Question 10

How does PLP bind to enzymes

Answer 10

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

Question 11

What are transaminases and what are they important for?

Answer 11

catalyze transamination reactions where AA
transfer amino group to α-keto acids
* interconversion of AA
* catabolism of AA
* synthesis of non-essential AA

Question 12

What is the role of PLP in transaminases?

Answer 12

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.

Question 13

What are decarboxylases and what are they important for?

Answer 13

AA decarboxylation - remove carboxyl groups (CO2H)
* hormone & neurotransmitter synthesis

Question 14

What is the role of PLP in decarboxylases?

Answer 14

Conversion requires vitamin B6 to make neurotransmitters

Question 15

What is the transulfuration pathway and the role of PLP in Trans- & desulfuration?

Answer 15

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

Question 16

Role of pyridoxine in Trp metabolism

Answer 16

The last enzyme in the process of converting Trp to nicotinamide, kynureninase, is PLP dependant
* Very important for Niacin status

Question 17

Role of PLP in heme synthesis

Answer 17

Involved in synthesis of heme via δ-aminolevulinate synthetase
* Rate limiting step in heme biosynthesis

dont memorize reaction

Question 18

Role of PLP in glycogenolysis

Answer 18

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

Question 19

Pyridoxine absorption and transport

Answer 19

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.

Question 20

Pyridoxine storage

Answer 20

• 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

Question 21

Why is the bulk of B6 stored in the muscle?

Answer 21

Glycogen phosphorylase, and bulk of AA metabolism is contained in the muscle

Question 22

Pyridoxine excretion

Answer 22

renal reabsorption

Question 23

pyrdoxine food sources

Answer 23

Widely distributed
* richest sources: meats & unprocessed cereals

Question 24

What are the forms of B6 in foods?

Answer 24

• animal tissue: PLP and PMP
• plant foods: PN
• supplements & fortified food: PN

Question 25

How might B6 be lost from foods?

Answer 25

• heating
• milling/processing (75-90% loss)
• long storage (~1 year) → 25-50% loss

Question 26

Bioavailability of B6

Answer 26

• Bioavailability in supplements is >90%
• Bioavailability in foods is ~75%

Question 27

Why is B6 bioavailibilty in foods less?

Answer 27

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

Question 28

What are B6 requirements based on?

Answer 28

Requirements related to protein intake

Question 29

B6 UL

Answer 29

UL = 100 mg/day
* high levels associated with sensory neuropathy

Question 30

B6 RDAs

Answer 30

M/F - 1.3 mg/d
* increases in pregancy and lactation

Question 31

Assessments for B6 status

Answer 31

• 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

Question 32

Prevalance of B6 deficiency

Answer 32

—Rare because of:
* wide distribution
* possibly available from gut flora synthesis

Question 33

How might B6 deficiency be present?

Answer 33

conditional deficiency not specific to B6
* defective intestinal absorption
* defective cellular & intercellular transport
* impaired oxidation or phosphorylation mechanisms

Question 34

signs/ symptoms of B6 deficiency

Answer 34

• hematological: microcytic anemia (related to folate metabolism), hyper-Hcy
• nervous system: ataxia, depression, convulsions
• skin: dermatitis, lesions

Question 35

Who is at risk for B6 deficiency?

Answer 35

• poor diet (Famine; but risk for all nutrients)
• drug-induced (Isoniazid; L-DOPA)
• Alcoholics

Question 36

How might alcoholism result in B6 deficiency?

Answer 36

• ↓ B6 status independently
• acetaldehyde ↓ cellular PLP levels by displacing PLP from bind proteins rendering the enzymes inactive

Question 37

Potential benefit of toxic dose of B6?

Answer 37

Possible (weak evidence) therapeutic effects on
* PMS
* depression

Question 38

Problems with B6 toxicity

Answer 38

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

Question 39

New research in B6

Answer 39

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.