Homocysteine biosynthesis

The mechanism of homocysteine biosynthesis by green plants received little attention until the classic isotope dilution experiments of Dougall and Fulton (1967), with cultured cells of Paul s Scarlet Rose, provided evidence... 

Fig. 4. Two pathways of homocysteine biosynthesis. Transsuifiiration is shown by heavy arrows, and direct suifhydration by the open arrow.

We recently proposed (Datko et al., 1977) that at least some homocysteine is indeed synthesized by direct sulfhydration. Further analysis indicates that, whereas our data are consistent with this possibility, it is also possible that mLemna all homocysteine biosynthesis is via transsulfuration. 

Early studies of homocysteine biosynthesis in plants were oriented largely by what was known in microorganisms. Microorganisms were known to synthesize homocysteine by transsulfura-tion, the transfer of sulfur between cysteine and homocysteine via cystathionine. In bacteria, transsulfuration proceeds only from cysteine to homocysteine, whereas in fungi transsulfuration proceeds reversibly between cysteine and homocysteine (Flavin, 1975). Our early studies therefore asked whether transsulfuration occurs in plants, and if so, in what direction it proceeds. 

These early studies raised two major questions that will be discussed below. The first is the nature of the physiological homoserine ester (a-aminobutyryl donor) that is used for cystathionine s3mthesis (Reaction (1)J and homocysteine S3mthesis (Reaction (3)J. The second is the relative physiological significance of the two pathways in homocysteine biosynthesis. 

Plants are Unique in Using Q-Phosphohomoserine as a Substrate for Cystathionine and Homocysteine Biosynthesis... 

These combined data strongly suggest that, regardless of the pathway, 0-phosphohomoserine is the physiologically important a-aminobutyryl donor for homocysteine biosynthesis. This conclusion is consistent with vivo experiments (Dougall and Fulton, 1967) that showed that neither 0-succinyl- nor 0-acetylhomoserine was utilized in preference to homoserine for cystathionine synthesis by cells of Paul s Scarlet Rose. 

At least 90% of homocysteine biosynthesis in this plant proceeds also through transsulfuration (P.M. Macnicol, A.H. Datko,... 

J. Giovanelli, and S.H. Mudd, unpublished results). The results with these two phylogenetically distant plants suggest that transsulfuration is the predominant, perhaps exclusive, pathway for homocysteine biosynthesis in the plant kingdom. 

Homocysteine biosynthesis requires the confluence of two pathways, one providing the 4-carbon moiety via 0-phosphohomo-serine, the other providing the sulfur moiety via cysteine (Fig. 3), Sach of the converging pathways contains two branch points, and additional branch points occur at threonine, methionine and AdoMet. A priori, two predictions can be made regarding the control patterns of homocysteine biosynthesis in the system. One is that the control patterns will be complex, in order that a fine balance can be maintained between the interlocking and multiply branched pathways. The second is that novel control patterns may occur... 

Datko, A. H., Giovanelli, J., and Mudd, S. H., 1974, Homocysteine biosynthesis in green plants. 0-Phosphohomoserine as the physiological substrate for cystathionine Y synthase, J. Biol. Chem., 249 1139. 

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