Neurospora Homoserine

The chemical reactions for the conversion of homoserine to a-ketobutyric acid in the vertebrate organism, if that is the pathway, are quite obscure. In Neurospora homoserine is the precursor of threonine (see the chapter, Synthetic Processes Involving Amino Acids, which in turn is deaminated to a-ketobutyric acid (see Fig. 3, reaction 4). The reaction sequence from homoserine to threonine probably is through/3-y-dihydroxy-a-aminobutyric acid as an intermediate. 

This enzyme [EC 1.1.1.3] catalyzes the reaction of homoserine with NAD(P) to produce aspartate 4-semialdehyde and NAD(P)H. NAD is the better of the two coenzymes with the yeast enzyme whereas NADP+ is preferred by the Neurospora enzyme. See also Aspartate Kinase... 

A more direct y replacement of the hydroxyl of homocysteine or 0-phosphohomoserine by a sulfide ion has also been reported for both Neurospora and green plants.Methylation of homocysteine to methionine (Fig. 24-13) has been considered previously, as has the conversion of homoserine to threonine by homoserine kinase and the PLP-dependent threonine synthase (p. 746, Fig. i4-7).254-255a standard PLP-requiring P elimination converts threonine to 2-oxobutyrate, a precursor to isoleucine (Fig. 24-13). ... 

Evidence from several lines of investigation indicated a relationship between L-aspartic acid and L-threonine. Studies with isotopically labeled acetate in yeast and bacteria showed that the distribution of label in the 4 carbon atoms of aspartate was the same as found in threonine. Both aspartate and homoserine were found to suppress incorporation of labeled CO2 into threonine, and the label of aspartate was found to appear in a corresponding position in threonine. Mutants of Neurospora and E. coli were found to use homoserine to form threonine other mutants accumulated homoserine, and in E. coli it was found that aspartate was converted to homoserine. In Lactobacilli threonine was found to minimize an aspartic acid requirement. All of these findings support a scheme of reversible reactions ... 

Chemical genetic experiments on Neurospora have shown that threonine and methionine have a common precursor. In fact, a mutant requiring both amino acids at once can satisfy this double requirement when L-homoserine is supplied. On the other hand a mutant whose only block is in the synthesis of methionine accumulates threonine and L-homoserine in ts mycelium. The idea of a single precursor has been confirmed with... 

Both isomers of both serine and threonine are deaminated by Neuro-spora extracts 225-228). The enzymes involved have been purified by Yanofsky and his associates 225-228). A specific D-serine and D-threonine dehydrase has been purified thirty-five- to fortyfold from this mold 2f ). An absolute requirement for pyridoxal phosphate was demonstrated. No requirement for AMP or glutathione could be demonstrated. Some indication of a metal requirement was observed. The preparation was not active with the li-isomers of serine and threonine or DL-homoserine and DL-homo-cysteine. The rate of deamination of D-threonine is very slow compared to that with L-serine. Activity was observed with D-glutamic acid and D-as-partic acid. Since other D-amino acids were not deaminated by the preparation, these results could not be due to a contamination with D-amino acid oxidase. Furthermore, when either of these amino acids was incubated in the presence of D-serine, the keto acid production was a summation of that for each substrate alone. Pyridoxal phosphate had no effect on keto acid formation from the dicarboxylic amino acids. It is of interest that D-amino acid oxidase of Neurospora does not attack D-serine or D-threonine (77). 

Homoserine has been shoum to be the common precursor of methionine and of threonine in Neurospora craaaa (7 ) and other microorganisms. This subject is discussed in Chapter 15. Homoserine has been found in various plants (7S). 

The first evidence that homoserine is the precursor of threonine was derived from the observations that L-homoserine could replace threonine and methionine in Neurospora mutants requiring the latter amino acids (95). In addition a Neurospora mutant blocked in methionine s3mthesis alone was found to accumulate threonine and homoserine (96). 

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