A History of Biochemistry: Selected Topics in the History of by Albert Neuberger, L. L. M. Van Deenen, Giorgio Semenza

By Albert Neuberger, L. L. M. Van Deenen, Giorgio Semenza

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A BACKWARD GLANCE 35 N,o " FORMYL THFA PURINE NUCLEOTIDES — NUCLEIC ACIDS N 5 N, 0 METHYLENE GLYCINE T H FA NADH SERINE NAD + METHIONtNE B,2 -CONTAINING METHYLTRANSFERASE HOMOCYSTEINE Fig. 4. Biosynthesis of methionine illustrating participation of tetrahydrofolate and vitamin B 12 derivatives; example of a metabolic trap (the methyl-tetrahydrofolate metabolic trap). Recently Fujii et al. [156] have performed elegant experiments with leukemia cells that confirm the metabolic trap hypothesis. Thus, after approx.

I was in that particular state in 1956 when we were just concluding our major thrust in characterizing our enzymes and reactions in purine synthesis. On the basis of the interesting preliminary results with azaserine, I had committed myself to an in-depth research program on one enzyme of the purine biosynthesis pathway, namely FGAR amidotransferase. Yet I could not foresee spending a lifetime in this same specific area. Up until my move to MIT my interests and approaches in research had been taken primarily from the point of view of a chemist.

M. BUCHANAN inosinic acid synthesis from hypoxanthine seemed to include the formation of inosine from ribose-1-phosphate and hypoxanthine catalyzed by nucleoside phosphorylase [71], followed by the phosphorylation of the nucleoside to the nucleotide. The latter kinase reaction had not been reported, however. We had found that radioactive hypoxanthine is readily equilibrated with nonisotopic inosinic acid in the presence of an extract of pigeon liver [72]. The latter was fractionated into two components, neither of which alone could catalyze the reaction [73].

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