One carbon transfers

Question 1

Methionine

Answer 1

formed from homocysteine
*requires vitamin B12 to donate a methyl group
OR
can be obtained by diet

Question 2

Folate

Answer 2

-gives CH3 group to cobalamin to regenerate methylcobalamin (vitamin B12)

-folate gets recycled back using riboflavin

Question 3

Methionine production

Answer 3

1.Methionine condenses with ATP to form SAM
2. Sam donates a methyl group to metabolic pathways and forms SAH
3.SAH is hydrolyzed to homocystein and adenosine
4.Homocystein can be remethylated to methionine by methionine synthase (needs vit B12)

Question 4

Vitamin B12 forms

Answer 4

1.methylcobalamin

2. cyanocobalamin (synthetic form)

Question 5

What occurs when no vitamin B12 present?

Answer 5

-homocysteine will accumulate because no methylcobalamin present to donate one carbon
-Results in a backup all the way down the chain and folate trap

Question 6

Folate trap

Answer 6

-No methylcobalamin (vit B12) present. Therefore no carbon given to homocysteine and no methionine produced.

If methylcobalamin is not donated, then no cobalamin is produced and therefore folate trap occurs because no cobalamin for methyl tetrahydrofolate to donate carbon to. Means no tetrahydrofolate production

Question 7

Physiological consequences of folate trap

Answer 7

-underlying conditions- very low supply of methionine starvation
-decreased methionine will slow production of tetrahydrofolate for DNA synthesis
-DNA biosynthesis and cell division is reduced thus reducing competition for Met. Met is used for production of SAM which is needed for myelin regeneration, NTs, carnitine

Question 8

Vitamine B12 deficiency

Answer 8

-impairs metabolism of folic acid leading to functional folate deficiency
>causes pernicious anemia (immature erythrocyte precursors are released in circulation)

Question 9

Most common causes of vitamin B12 deficiency

Answer 9

-failure of absorption of Vit B12 due to lack of intrinsic factor
-secondary cause is dietary deficiency OR autoimmune disease affecting parietal cells or anti-intrinsic factor antibody production

Question 10

Pernicious anemia

Answer 10

results in irreversible degradation of the spinal cord due to failure of methylation of an arginine residue on myelin protein from methionine deficiency

Question 11

Elevated homocysteine

Answer 11

associated with cardiovascular disease.

**B12 vitamine therapy may reduce symptoms

Question 12

General vitamin information

Answer 12

-water soluble vitamins have little in common
-most synthesized in animal cells
-most absorbed in small intestine
-most carried in the blood n free form, but some bound to proteins
-excreted in urine (EXCEPT vit B12 which is lost in feces)

Question 13

Choline

Answer 13

-technically not a vitamin
-from meats, nuts, eggs
or obtained via breakdown of phospholipids
-absorbed by enterocytes

**precursor to betaine which is needed for homocysteine to methionine conversion

Question 14

Folate (Vit B9)

Answer 14

-carry one-carbon units bound to one or two nitrogen atoms

-absorbed via H+ carrier dependent mechanism

-important for DNA synthesis
-works with B12 and B6 to maintain normal concentration of homocysteine

-found in legumes, green leaky vegetables, fortified breads

-deficiency causes megaloblastic anemia

Question 15

Vitamin B12 (cobalamin)

Answer 15

-complex molecule with a cobalt ion at the centre in the liver exists primarily as methyl cobalamin (OR cyanocobalamin if synthetic)

-free form sensitive to acid

-seafood, poultry, red meat OR synthesized by microbes

**deficiency due to inadequate intake or B12 malabsorption

Question 16

Vitamin B12 absorption

Answer 16

Gastric phase
-release of B12 from proteins, binds to endogenous carriers (haptocorrin, intrinsic factor)

Duodenal phase
-HC-B12 is partially degraded
- IF-B12 remains intact. Low absorption without IF. Primarily absorbed in ileum.

**significant losses often seen in feces

Question 17

Intrinsic factor

Answer 17

-produced by gastric mucosal cells in most species
-But mostly pancreas in dogs, and only pancreas in cats

Question 18

Failure to absorb Vitamin B12 in dogs

Answer 18

• occurs due to absence of cobalamin-IF complex in lower intestines

-affects giant schnauzers, border collies, beagles

-presents the same as folic acid deficiency BUT folate treatment would be problematic because folate is already present and trapped. Will cause increased accumulation.

Question 19

Causes of B12 malabsorption

Answer 19

-intrinsic factor deficiency
-Addison’s disease (impaired gastric acid secretions)
-Bariatric surgery (impaired IF and gastric acid secretion)
-Pancreatic insufficiency
-Inflammatory bowel diseases
-drugs