Amino acids as methyl donors in Methylation Rxns

Question 1

One-carbon cycle + methyl cycle

Answer 1

Question 2

Serine is converted to glycine by

Answer 2

serine hydroxymethyl transferase (SHMT) which has no activity and relies on its cofactors (PLP and tetrahydrofolate) and produced formaldehyde in the rxn

Question 3

Methyl group of formaldehyde is transferred to

Answer 3

tetrahydrofolate

Question 4

Explain the reduction of 5,10-methylene-THF in the on-carbon cycel

Answer 4

Question 5

S-Adenosyl Methionine (SAM) is synthesized by (Methyl Cycle)

Answer 5

Methionine adenosyl transferase which uses a condensation rxn at 5’ carbon of the ribose

Question 6

SAM is a

Answer 6

major methyl donor in many transmethylation reactions

Question 7

S-adenosyl-homocysteine is broken down to

Answer 7

Homocysteine

Question 8

S-adenosyl-homocysteine is broken down to

Answer 8

Homocysteine

Question 9

homocysteine is converted to [blank] by what process

Answer 9

Methionine by acquiring a methyl group from folate and is catalyzed by methionine synthetase
-5-methyl THF is the methyl donor and will be converted back to THF
-Coenzyme B12 (Vitamin B12) is necessary for this rxn

Question 10

Methyl Cycle

Answer 10

Question 11

What is the effect of the MTHFR genotype on the methyl cycle

Answer 11

1) Variant 677CT (alanine to valine) and 1298AC (glutamate to alanine) were shown to decrease MTHFR activity.
2) 677TT homozygote or 677CT/1298AC heterozygote were shown to contribute to the development of hyperhomocysteinemia.
-Stroke, cerebrovascular disease, coronary artery disease and thrombophilic disease.
3) MTHFR variants, birth control, migraine and increased risk thromboembolic disease.

Question 12

CASE STUDY: Vegetarian diets can provide high levels of antioxidants and a lipid profile that can help prevent coronary disease. However, there can be some associated problems.

Blood samples were taken from a large group of volunteer subjects who were:

Vegans (strict vegetarians, no animal products)
Lactovegetarians (vegetarians who eat dairy products)
Omnivores (varied diet, including meat)

In each case, the volunteers had followed the diet for several years. The blood levels of homocysteine were elevated in the vegan group, somewhat lower in the lactovegetarian group and much lower in the omnivore group.

Answer 12

-Vegan diet is low in vitamin B12 so they need fortified cereals and soy products
-dairy products, egg and meat (fish) provide some source of vitamin B12 for nonvegan

Question 13

Hyperhomocysteinemia: the “methyl trap” is caused by

Answer 13

low levels of:
-Vitamin B12
-Folic acid
-…Vitamin B6!!! (The active form of vitamin B6 is called pyridoxal 5′-phosphate)

Question 14

Hyperhomocysteinemia illness causes

Answer 14

1) Cardiovascular risks
2) Cardiovascular disease
3) Thrombosis
4) Neuropsychiatric illness
5) Link to Alzheimer’s disease, schizophrenia and dementia
6) Increased incidence of fractures in older persons.

Question 15

Protein and DNA methylation

Answer 15

Question 16

Protein methylation occurs where and how many times at each site

Answer 16

1) Arg: can be methylated once (monomethylated) or twice (asymmetrically or symmetrically dimethylated)
2) Lys: can be methylated once, twice, or three times

Question 17

Histone methylation results in

Answer 17

repression or activation of gene expression - epigenomics

Question 18

Methylation of histone H3 tail on lysine K4 3 characteristics

Answer 18

-Associated with gene expression
-Monomethylated H3K4me1 were found in promoter-distal sites
-Trimethylated H3K4me3 were mainly found at the proximal promoter.

Question 19

Methylation of histone H3 tail on lysine K4 3 characteristics

Answer 19

-Associated with gene expression
-Monomethylated H3K4me1 were found in promoter-distal sites
-Trimethylated H3K4me3 were mainly found at the proximal promoter.

Question 20

Where does DNA methylation occur in prokaryotes

Answer 20

Argenine and cytosine

Question 21

What does DNA methylation in prokaryotes do

Answer 21

Prevents foreign DNA insertion through DNA-MTases (DNA methyltransferases) and having a distinct methylation pattern:
-Proper methylation pattern = endogenous DNA
-Improper methylation pattern = exogenous DNA (Danger for the cell)
-Endonucleases will cleave non-methylated DNA fragments.

Question 22

How does DNA methylation occur in eukaryotes

Answer 22

Cytosine is methylated at CpG island within promoter regions to convert into 5-methyl cytosine

Question 23

How does DNA methylation occur in eukaryotes

Answer 23

Cytosine is methylated at CpG island within promoter regions to convert into 5-methyl cytosine