The dUMP Suppression Test

3 The dUMP Suppression Test Rapidly dividing ceUs can either use preformed TMP or can synthesize it de novo from dUMP. Isolated hone marrow cells or stimulated lymphocytes incubated with pH]TMP wUl incorporate label into DNA. In the presence of adequate amounts of methylene-tetrahydrofolate, the addition of dUMP as a substrate for thymidylate synthetase reduces the incorporation of pH] TMP as a result of dUution of the pool of labeled material by newly synthesized TMP. 

The extent to which dUMP suppresses the incorporation of [ H]TMP into DNA thus reflects folate nutritional status (Section 10.10.5). 

In addition to its role in the synthesis of proteins and the polyamines spermidine and spermine, the main metabolic role of methionine is as a methyl donor in a wide variety of biosynthetic reactions. 

There are two separate homocysteine methyltransferases in most tissues. One uses methyl-tetrahydrofolate as the methyl donor and has vitamin B12 (cohalamin Section 10.8.1) as its prosthetic group. This enzyme is also known as methionine synthetase it is the only homocysteine methyltransferase in the central nervous system. The other enzyme utilizes hetaine (an intermediate in the catabolism of choline Section 14.2.1) as the methyl donor and does not require vitamin B12. 

Unlike most enzymes utilizing or metabolizing tetrahydrofolate, methionine synthetase has equal activity toward methyl-tetrahydrofolate mono- and polyglutamates. As discussed in Section 10.2.2, demethylation of methyl-tetrahydrofolate is essendal for the polyglutamylation and intracellular accumulation of folate. 

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A serum concentration of vitamin B below llOpmol/L is associated with megaloblastic bone marrow, incipient anaemia and myelin damage. Below 150pmol/L there are early bone marrow changes, abnormalities of the dUMP suppression test (section 11.11.6.2) and methylmalonic aciduria after a valine load (section 11.10.2). 

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