Biochemistry Exams - 2008/2009 3rd year Undenominated Science Semester I - Question 5

Welcome Again in the Biochemistry Exam Exposed Section,

Today we will expose Question 5 from this exam paper 2008/2009 3rd year Undenominated Science Exam Paper Semester I.

Question 5 sounds... “Modest elevations of homocysteine have multiple causes, including low levels of folic acid, vitamins B6 and B12”. Expand on the metabolic bases to this statement.

Short, short background;

homocysteine - is a homologue of aminoacid cysteine differing by an additional methylene (-CH₂-) group.

Check the figure below.

 

Homocysteine is synthesized from methionine (figure above) by removing the terminal methylene group (CH3-). On the other hand homocysteine can be recycled to give cysteine or methionine.

Answer to Question 5 lies in the methabolic pathways that deal with homocysteine degradation. So, biosynthesis of homocysteine (see figure below) starts from the methionine which first is conjugated with ATP to form S-adenosyl methionine. In the second step methyl group which is bonded to sulphur atom is transfered to acceptor molecule (norepinephrine which is converted to epinephrine). In the third step adenosine (ATP residue) is hydrolized what gives homocysteine.

 

Probably at this stage some of you wonder why the methyl group from the methionine, is simply removed to give the homocysteine. It requires addition of adenosine first beacuse it makes the methyl group higly labile. In the case of methionine, the methyl group is too stable to be transfered.

Homocysteine can be transformed back to methionine or to cysteine. The former requires THF (tetrahydrofolate) a folic acid or or cyanocobalamin (vitamine B12) and latter pyridoxine (vitamine B6) as enzyme coffactors. So simply saying if there is no folic acid, vitamin B12 and B6 available in the body, enzymes that requires those molecules for proper function cannot fulfill their roles. If they are not able to catalyse reactions mentioned above homocysteine levels will raise.

You can also include in the answer what are the consequences of such elevation.

It is known that increased homocysteine levels cause cardiovascular diseases. How this can happen? Scientists believe that homocysteine simply degrades proteins like collagen and elastin (artery proteins) because it competes with the cystein to form disulfide bonds.

This is it:)

Question 6 soon.

Maciek GGSTEAM