4 B6 and B12 Flashcards
6 related compounds of B6
pyridoxal, pyridoxine, pyridoxamine
- and their phosphates
B6 phosphorylated in..
foods
B6’s phosphate removed by
intestinal enzymes
B6 absorption
well absorbed passively
Process that occurs when B6 is absorbed by tissues
re-phosphorylated in tissue
Urinary excretion metabolite of B6
4-pyridoxic acid
B6 coezyme form
pyridoxal phosphate (PLP)
Vitamin needed to convert pyridoxine (related B6 compound) to pyridoxal phosphate (PLP)
riboflavin
PLP
pyridoxal phosphate
- coenzyme of B6
- over 100 PLP dependent enzymes
- amino acid metabolism
Primary role of B6
- amino acid metabolism
- Intermediary metabolism (GNG)
- Tryptophan metabolism
- synthesis of niacin (ribo also needed - kyneurine pathway)
Schiff Base
PLP binds to “lysine” on enzymes via schiff base
- link formed between PLP aldehyde and enzyme amino group (lysine)
- forms IMINE group
R-C=N-R’
B6 roles in metabolism
amino acid metabolism
nervous system
- synthesis of neurotransmitters
hormone function
- inhibits by binding to receptors
glycogen breakdown
- glycogen phosphorylase coenzyme
red blood cell formation and function
- synthesis of heme
Immune function
- not clear
Amino acid that seratonin is synthesized from
tryptophan
How does B6 affect hormone function
PLP binds to steroid hormone receptors to decrease the effects
PLP role in glycogen breakdown
Coezyme for glycogen phosphorylase
- key enzyme converting glycogen to glucose (glycogenolysis)
PLP role in Red blood cell formation and function
Positive:
Coenzyme for synthesis of heme (part of hemoglobin)
Negative:
Pyridoxal (PL) and Pyridoxal Phosphate (PLP) can bind to hemoglobin molecule - affect pick of and release of O2 (affect not known)
PLP role in immune function
- coenzyme for mobilization of single carbon functional groups
- Serine OH-methyltransferase
- synthesis DNA/RNA
- Deficiency decrease IL-2, decreased lymphocyte proliferation
** not well known
***Assessing Vitamin B6 status
- **Load Tests:
- Tryptophan load test
- Methianine Load Test
Other:
4-Pyridoxic acid in urine
- absent in deficiency
Why can’t we use B6 intake when assessing B6 status
Intake doesn’t consider the bioavailability
Vit B6 deficiency
- Nervous system:
- irritability, depression, confusion
- sleeplessness
- abnormal EEG patterns (measuring electro-activity around the scalp) - Dermatitis, cheilosis, stomatitis
Vit B6 deficiency similar to what other deficiency
Riboflavin
- both needed in kynurenine pathway
- riboflavin needed for B6 coenzyme form
B6 Requirement affected by?
Protein intake
- B6 main role in amino acid metabolism
Oral contraceptives
Alcoholism
Pregnancy and lactation
- last 2 affect almost everything
B6 food sources
fortified cereals
meats
grains
legumes
B6 loss in food caused by?
Milling
as with other B vitamins
B6 drug interactions
High doses B6 can ‘decrease’ efficacy of:
- Anti-TB meds (tuberculosis)
- Anti-Convulsant meds (epilepsy)
B6 forms complexes with drugs, causing B6 deficiency
B6 involved in what Health/Disease factors
CVD
- homocysteine Hcy build up is a sign of CVD
- PLP needed conversion Hcy to cysteine
Immune Function
- low B6 associated w impaired immune function (particularly in elderly)
Cognitive Function
- Decline w low B6 (also folate and B12)
- Memory?
Depression
- PLP-dependent neurotransmitter serotonin
PMS
-relieves symptoms
Others: Morning sickness, carpal tunnel, kidney stones
Largest, most complex structure of the B vitamins?
B12
Center of B12 structure
cobalt
B12 also called
Cobalamin
B12 structures
R group off of the centre cobalt
R=Methyl
- methyl-cobalamin
R=Adenosyl
- 5’-deoxyadenosyl-cobalamin
R=CN (synthetic form)
- Cyanocobalamin
*KNOW THESE
B12 absorption
3 phase process:
- gastric phase
- luminal phase
- mucosal phase
depends on pH and presence of receptors
Intrinsic Factor (IF) and B12
key to B12 absorption
- glycoprotein released to stomach by parietal cells
- binds B12
- allows passage into ileum
- Ilium has receptor for IF-B12
Gastric phase B12 absorption
1st phase (stomach)
Digests protein bound B12
Free-cobalamin binds R-proteins
- high affinity
- IF doesn’t bind at this point
Luminal Phase B12 absorption
2nd phase (duodenum)
R-proteins digested and Free cobalamin, now combine with IF (released by parietal cells)
Mucosal phase B12 absorption
3rd (final) phase (ileum)
IF-B12 bind receptors in the Ileum
Absorption occurs
B12 metabolic role
Methyl Cobalamin:
mehtionine synthetase
- Hcy to methionine (also need folate)
Adenosyl Cobalamin: methylmalonyl CoA mutase - propionate catabolism - propionate -> **methymalonyl CoA --> succinyl CoA - enters TCA cycle
**methylmalonyl CoA (MMA) only way to measure metabolism
Factors affecting B12 absorption
Atrophic Gastritis
- decrease gastric acid
- age related decrease in parietal cells
Decreased Intrinsic Factor
- age related decrease parietal cells
Pancreatic Insufficiency
- decreased protein absorption
B12 deficiency
Pernicious Anemia
- lack of IF
- diagnosed with Schilling Test (radioactively labels cobalt)
- B12 injection treatment (skips absorption)
Neurological problems
- memory loss, demetia, weakness, tiredness
- 7 years to develop
- can be irreversible
Urinary signs of B12 deficiency
elevated levels of
- homocysteine
- methymalonic acid***
B12 defeciency / folate relation
Folate masks B12 deficiency
- both folate and B12 deficiency cause macrocytic anemia
- folate can correct the anemia of B12 deficiency but NOT neurological symptoms
How “breath test” can asses B12 status`better
- Examines rate of oxidation of 13C-propionate to 13CO2 in breath
- C13 label on propionate is used and CO2 in breath is measured
- B12 coenzyme role in propionate catabolism
B12 food sources
Animal sources only
Some B12 synthesized by anaerobic microorganism (algae)
