4 B6 and B12

Question 1

6 related compounds of B6

Answer 1

pyridoxal, pyridoxine, pyridoxamine

- and their phosphates

Question 2

B6 phosphorylated in..

Answer 2

foods

Question 3

B6’s phosphate removed by

Answer 3

intestinal enzymes

Question 4

B6 absorption

Answer 4

well absorbed passively

Question 5

Process that occurs when B6 is absorbed by tissues

Answer 5

re-phosphorylated in tissue

Question 6

Urinary excretion metabolite of B6

Answer 6

4-pyridoxic acid

Question 7

B6 coezyme form

Answer 7

pyridoxal phosphate (PLP)

Question 8

Vitamin needed to convert pyridoxine (related B6 compound) to pyridoxal phosphate (PLP)

Answer 8

riboflavin

Question 9

PLP

Answer 9

pyridoxal phosphate

• coenzyme of B6
• over 100 PLP dependent enzymes
• amino acid metabolism

Question 10

Primary role of B6

Answer 10

• amino acid metabolism
• Intermediary metabolism (GNG)
• Tryptophan metabolism
• synthesis of niacin (ribo also needed - kyneurine pathway)

Question 11

Schiff Base

Answer 11

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’

Question 12

B6 roles in metabolism

Answer 12

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

Question 13

Amino acid that seratonin is synthesized from

Answer 13

tryptophan

Question 14

How does B6 affect hormone function

Answer 14

PLP binds to steroid hormone receptors to decrease the effects

Question 15

PLP role in glycogen breakdown

Answer 15

Coezyme for glycogen phosphorylase

- key enzyme converting glycogen to glucose (glycogenolysis)

Question 16

PLP role in Red blood cell formation and function

Answer 16

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)

Question 17

PLP role in immune function

Answer 17

• coenzyme for mobilization of single carbon functional groups
• Serine OH-methyltransferase
• synthesis DNA/RNA
• Deficiency decrease IL-2, decreased lymphocyte proliferation

** not well known

Question 18

***Assessing Vitamin B6 status

Answer 18

• **Load Tests:
• Tryptophan load test
• Methianine Load Test

Other:
4-Pyridoxic acid in urine
- absent in deficiency

Question 19

Why can’t we use B6 intake when assessing B6 status

Answer 19

Intake doesn’t consider the bioavailability

Question 20

Vit B6 deficiency

Answer 20

1. Nervous system:
   - irritability, depression, confusion
   - sleeplessness
   - abnormal EEG patterns (measuring electro-activity around the scalp)
2. Dermatitis, cheilosis, stomatitis

Question 21

Vit B6 deficiency similar to what other deficiency

Answer 21

Riboflavin

• both needed in kynurenine pathway
• riboflavin needed for B6 coenzyme form

Question 22

B6 Requirement affected by?

Answer 22

Protein intake
- B6 main role in amino acid metabolism

Oral contraceptives
Alcoholism
Pregnancy and lactation

• last 2 affect almost everything

Question 23

B6 food sources

Answer 23

fortified cereals
meats
grains
legumes

Question 24

B6 loss in food caused by?

Answer 24

Milling

as with other B vitamins

Question 25

B6 drug interactions

Answer 25

High doses B6 can 'decrease' efficacy of: - Anti-TB meds (tuberculosis) - Anti-Convulsant meds (epilepsy) B6 forms complexes with drugs, causing B6 deficiency

Question 26

B6 involved in what Health/Disease factors

Answer 26

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

Question 27

Largest, most complex structure of the B vitamins?

Answer 27

B12

Question 28

Center of B12 structure

Answer 28

cobalt

Question 29

B12 also called

Answer 29

Cobalamin

Question 30

B12 structures

Answer 30

R group off of the centre cobalt R=Methyl - methyl-cobalamin R=Adenosyl - 5'-deoxyadenosyl-cobalamin R=CN (synthetic form) - Cyanocobalamin *KNOW THESE

Question 31

B12 absorption

Answer 31

3 phase process: - gastric phase - luminal phase - mucosal phase depends on pH and presence of receptors

Question 32

Intrinsic Factor (IF) and B12

Answer 32

key to B12 absorption - glycoprotein released to stomach by parietal cells - binds B12 - allows passage into ileum - Ilium has receptor for IF-B12

Question 33

Gastric phase B12 absorption

Answer 33

1st phase (stomach) Digests protein bound B12 Free-cobalamin binds R-proteins - high affinity - IF doesn't bind at this point

Question 34

Luminal Phase B12 absorption

Answer 34

2nd phase (duodenum) R-proteins digested and Free cobalamin, now combine with IF (released by parietal cells)

Question 35

Mucosal phase B12 absorption

Answer 35

3rd (final) phase (ileum) IF-B12 bind receptors in the Ileum Absorption occurs

Question 36

B12 metabolic role

Answer 36

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

Question 37

Factors affecting B12 absorption

Answer 37

Atrophic Gastritis - decrease gastric acid - age related decrease in parietal cells Decreased Intrinsic Factor - age related decrease parietal cells Pancreatic Insufficiency - decreased protein absorption

Question 38

B12 deficiency

Answer 38

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

Question 39

Urinary signs of B12 deficiency

Answer 39

elevated levels of - homocysteine - methymalonic acid***

Question 40

B12 defeciency / folate relation

Answer 40

Folate masks B12 deficiency - both folate and B12 deficiency cause macrocytic anemia - folate can correct the anemia of B12 deficiency but NOT neurological symptoms

Question 41

How "breath test" can asses B12 status`better

Answer 41

- 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

Question 42

B12 food sources

Answer 42

Animal sources only Some B12 synthesized by anaerobic microorganism (algae)