Biochem 3-9 Sam/folate/b12 Metaolism & Epigenetics

Front 1

Folate and s-adenosylmethionine (SAM) are needed for:

Back 1

transfer of one-carbon groups

Front 2

Folate structure

Back 2

Pteridine ring + PABA + glutamate; usually has chain of glutamates attached

Front 3

T/F: Folate can be synthesized in the body.

Back 3

False; synthesized by bacteria and higher plants

Front 4

In the intsestine, all _____ residues on folate except one are cleaved off.

Back 4

glutamate

Front 5

Folic acid found in supplements is in the _____ form.

Back 5

monoglutamate

Front 6

What steps in folate activation does dihydrofolate reductase (DHFR) take part?

Back 6

Folate → FH2 (dihydrofolate) → FH4 (tetrahydrofolate)

Front 7

What happens to FH4 (tetrhydrofolate) follwing the 2nd reduction by DHFR?

Back 7

gets reconjugated to polyglutamae form in the liver (for storage) or in other tissues

Front 8

Which form of folate can accept one-carbon groups?

Back 8

the conjugated, polyglutamate tetrahydrofolate (FH4) form

Front 9

Name 3 synthetic processes that require folate one-carbon transfers:

Back 9

-Purine and dTMP synthesis
-Serine synthesis
-Methylcobalamin synthesis

Front 10

What two processes what be directly impaired by folate deficiency?

Back 10

DNA synthesis and cell division

Front 11

What happens to folate after it hands of its one-carbon group?

Back 11

gets recycled to accept a new carbon

Front 12

What is the most stable form of folate and therefore the form which tends to accumulate?

Back 12

N5-methyl-FH4

Front 13

How is N5-methyl-FH4 recycled?

Back 13

transfers its carbon to vitamin B12

Front 14

Vitamin B12 is also called _____.

Back 14

cobalamin; corrin ring + cobalt

Front 15

How is cobalamin synthesized? What are the major sources for humans?

Back 15

synthesized by bacteria only; human sources are meat, eggs, dairy, and seafood... the sources get it from ingested bacteria

Front 16

What form of B12 is found in most supplements?

Back 16

cyanocobalamin; does not occur naturally

Front 17

What is B12 converted to following ingestion?

Back 17

methyl cobalamin or deoxyadenosylcobalamin

Front 18

B12 absorption requires _____ carriers.

Back 18

protein

Front 19

B12 absorption (1):

Back 19

Front 20

B12 absorption (2):

Back 20

Front 21

What two reactions require B12?

Back 21

-Transfer of methyl group from N5-methyl-FH4 to homocysteine to form methionine
-Conversion of methylmalonyl-CoA to Succinyl CoA

Front 22

Methionine/Succinyl CoA pathway

Back 22

Front 23

Conversion of methylmalonyl-CoA to succinyl-CoA requires _____.

Back 23

adenosylcobalamin

Front 24

What molecules builds up in the absence of adenosyl B12?

Back 24

methylmalonyl-CoA

Front 25

methylmalonic acid diagnostic

Back 25

Front 26

Remethylation of homocysteine to form methionine requires _____.

Back 26

methylcobalamin (methyl B12)

Front 27

You need _____ to make methyl-B12.

Back 27

folate

Front 28

_____ accumulates in methyl-B12 deficiency.

Back 28

homocysteine

Front 29

SAM donates a _____ group in several important reactions.

Back 29

methyl

Front 30

Where does SAM come from?

Back 30

methionine metabolism

Front 31

What processes require methyl donation by SAM?

Back 31

-creatine synthesis
-neurotransmitter synthesis
-DNA methylation
-histone synthesis

Front 32

What diseases ricks are associated with hyperhomocysteinemia?

Back 32

-CV disease
-infertility
-miscarriage
-neurological disorders
-cancer

Front 33

Would homocysteine go up or down: MTHFR deficiency

Back 33

up

Front 34

Would homocysteine go up or down: B12 deficiency

Back 34

up

Front 35

Would homocysteine go up or down: Folate deficiency

Back 35

up

Front 36

Would homocysteine go up or down: B6 deficiency

Back 36

up

Front 37

Would homocysteine go up or down: Cystathionine synthase deficiency

Back 37

up

Front 38

Would homocysteine go up or down: Excess SAM supplementation

Back 38

up

Front 39

MTHFR

Back 39

Front 40

What supplements may be able to reduce homocysteine levels?

Back 40

B12, B6, folate, betaine & choline

Front 41

Betaine & Choline

Back 41

Front 42

B12 or folate deficiencies can lead to _____ anemia.

Back 42

macrocytic

Front 43

Why does B12 deficiency cause macrocytic anemia if i is not needed for replication?

Back 43

methyl trap hypothesis

Front 44

How does the methyl trap hypothesis explain how B12 affects DNA replication?

Back 44

The most stable form of folate is the n5-methyl form.
The methyl can only be removed in one rxn (donation to B12).
If B12 or met synthase are deficient, N5-methyl-FH4 will build up resulting in a functional folate deficiency (plenty of folate is around but in a form that can’t be used).

Front 45

Folate deficiency during pregnancy increases the risk of _____ defects.

Back 45

neural tube defects:
-Primary mechanism believed to be through effects on DNA replication
-B12 deficiency may also be associated with neural tube defects

Front 46

Causes of B12 and folate deficiency:

Back 46

-Dietary insufficiency
-Chronic alcoholism
-Abdominal surgery can cause a decrease in IF production
-GI Disease (Crohn’s, celiac disease, Whipple disease)
-Intestinal parasites
-Certain drugs
-Intrinsic factor deficiency (called pernicious anemia)
** the first two are assoc. w/ both, the rest primarily assoc. w/ B12

Front 47

What 4 diagnostic tests can indicate B12 and folate deficiency?

Back 47

-serum B12 and folate levels
-CBC/Diff: MCV (mean corpuscular volume)= packed cell volunme/rbc count; elevated MCV suggests macrocytic anemia
-serum homocysteine and methylmalonic acid levels
-Schilling test

Front 48

Why is B12 deficiency more commonly seen in the elderly?

Back 48

-Malabsorption caused by gastric atrophy, long term use of certain drugs, H. pylori infection
--Reduced acid or pepsin secretion results in less B12 freed from haptocorrin
--Decreased IF production
-Inadequate diet
-May see neurological symptoms in the absence of anemia

Front 49

How must B12 and folate supplements be administered in pernicious anemia?

Back 49

via injection, nasal spray or high oral dosing

Front 50

Schilling test

Back 50

absorption of chrystaliline 12

Front 51

Why is DNA methylation important?

Back 51

-Genetic imprinting
-X-chromosome inactivation
-Retrotransposon silencing
-Dynamic regulatin of gene expression

Front 52

Maintenance methylation:

Back 52

addition of methyl groups to the daughter strand of hemi-methylated DNA

Front 53

De novo methylation

Back 53

addition of new methyl groups where there previously were none

Front 54

DNA and histone methyltransferases require _____ as the methyl donor.

Back 54

SAM

Front 55

Several studies have suggested that _____ may be associated with changes in DNA methylation patterns.

Back 55

hyperhomocysteinemia

Front 56

epigenetics

Back 56

an epigenetic trait is a heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence

Front 57

active demethylation

Back 57

enzymatic removal of methyl groups and its existence in mammals has only recently been demonstrated

Front 58

passive demthylation

Back 58

replication in the absence of the maintenance methyltransferase that adds methyl groups to hemi-methylated DNA