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Biomedical subjects

S H Mudd

Publications and source records attributed to S H Mudd.

At least 91 records · Page 5Linked to original sources
PubMed1975

Labile methyl balances for normal humans on various dietary regimens.

Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.

Adolescent↗
PubMed1975

Homocystinuria due to cystathionine synthase deficiency. Studies of nitrogen balance and sulfur excretion.

Apparent nitrogen balances and urinary sulfur excretions were determined for normal subjects, seven cystathionine synthase-deficient patients, and a single cystathioninuric patient on semisynthetic diets containing low-adequate amounts of methionine and very low amounts of methionine and very low amounts (12 mg daily, or less) of cystine. The amounts of supplemental cystine required to prevent abnormally high nitrogen or sulfur losses were determined. The five cystathionine synthase-deficient patients who had low residual activities of this enzyme detected in fibroblast and/or liver extracts did not lose more nitrogen or sulfur on diets virtually devoid of cystine than did the normal subjects. These results suggest that the widely expressed opinion that cystine is an essential amino acid for cystathionine syntase-deficient patients requires modification. Residual enzyme activity of only a few percent of normal may obviate such a cystine requirement. These results are compatible with, and lend support to, the working hypothesis which states that the pyridoxine response in cystathionine synthase-deficient patients is mediated by an increase in the residual activity of the affected enzyme.

Adolescent↗
PubMed1974

Homoserine esterification in green plants.

EXTRACTS OF PHYLOGENETICALLY DIVERSE PLANS WERE SURVEYED FOR THEIR ABILITY TO SYNTHESIZE THE FOLLOWING HOMOSERINE ESTERS WHICH ARE POTENTIAL PRECURSORS FOR METHIONINE AND THREONINE SYNTHESIS IN GREEN PLANTS: O-acetyl-, O-oxalyl-, O-succinyl-, O-malonyl-, and O-phosphohomoserine. Synthesis of O-acylhomoserine esters was detected only in Pisum sativum L. and Lathyrus sativus L. Extracts of P. sativum, a plant known to accumulate O-acetylhomoserine, catalyzed the specific synthesis of this ester from homoserine and acetyl-CoA. Extracts of L. sativus, a plant known to accumulate O-oxalylhomoserine, catalyzed the specific synthesis of this ester from homoserine and oxalyl-CoA. None of the other plants surveyed, including representatives of the green algae, horsetails, gymnosperms, and angiosperms, catalyzed the synthesis of any of the O-acylhomoserine esters studied. In contrast, synthesis of O-phosphohomoserine by the reaction catalyzed by homoserine kinase was demonstrated in extracts of all plants examined, including the two exceptional legumes.These results suggest that, among the five homoserine esters studied, O-phosphohomoserine is the major activated homoserine derivative in plants. Direct confirmation of the dominant physiological role of O-phosphohomoserine in the synthesis of cystathionine in the transsulfuration pathway of methionine biosynthesis in plants has recently been provided (Datko, A. H., Giovanelli, J., and Mudd, S. H. 1974. J. Biol. Chem. 249: 1139-1155).

Journal Article↗
PubMed1974

Inborn errors of metabolism. Vitamin-responsive genetic disease.

The several ways in which vitamin administration may bring about a biochemical response in genetic abnormalities have been discussed. Two major interrelated lessons emerge from what we now know about vitamin-responsive genetic disease. First, it is possible to enhance metabolite flow through partially deficient reactions by suitable manipulation of the environment in which a fixed amount of enzyme functions or by changing the concentration of the enzyme itself. The latter approach may be the most versatile in the long run since there may be agents other than vitamins which increase enzyme concentrations. A striking example of such an effect in mammals is furnished by the work of Pitot and his collaborators, who by administration of casein hydrolysate to rats, increased threonine dehydratase activity several hundred-fold (Peraino and Pitot, 1964) by increasing the rate of enzyme synthesis (Jost, Khairallah, and Pitot, 1968). Other means of enhancing enzyme activities, ranging from tissue transplantation to transfer of genetic material, have been discussed elsewhere (for example, see Brady, 1973). These procedures will not be discussed here, other than to mention a recent report (Mukherjee and Krasner, 1973) who transferred several small plugs of liver tissue (approximately 5% of the liver) from normal rats to the livers of rats genetically deficient in bilirubin uridine diphosphate glucuronyltransferase activity. Twelve weeks later the specific activity of glucuronyltransferase had risen in the livers of the recipient rats to 6-23% of normal, and the serum bilirubin of these rats, which had initially been elevated, had fallen to close to, or within, the normal range. Thus liver grafts between suitably matched individuals, may in the near future, become a means of increasing hepatic activities of deficient enzymes to extents which are therapeutically meaningful. The second lesson to be learned from the review presented here is that enhancement of enzyme activity may be therapeutically beneficial even though the increase is small and the activity attained is still reduced relative to normal. It will be well to bear this in mind in any attempts to treat inborn errors of metabolism.

Animals↗
PubMed1973

beta-Cystathionase In Vivo Inactivation by Rhizobitoxine and Role of the Enzyme in Methionine Biosynthesis in Corn Seedlings.

Rhizobitoxine has previously been shown to inactivate irreversibly beta-cystathionase isolated from spinach. In the present studies, rhizobitoxine was shown to inhibit partially beta-cystathionase of spinach and corn seedlings in vivo. An activity of 30 to 40% of normal remained in toxin-treated seedlings of both spinach and corn. Possible reasons for the partial inhibition are discussed.Rhizobitoxine-treated and control corn seedlings were allowed to assimilate (35)SO(4) (2-) for 3 or 6 hours, and the radioactivity incorporated into sulfur amino acids at these times was studied. The most striking effect of rhizobitoxine was an increase (up to 22-fold) in radioactive cystathionine. Accumulation of radioactivity in methionine was only slightly inhibited by rhizobitoxine treatment. The results strongly suggest that the transsulfuration pathway contributes to methionine biosynthesis, and that metabolism via this pathway is impaired, but not entirely eliminated, by rhizobitoxine treatment.The present data do not permit decisions about the relative contributions of the transsulfuration and the direct sulfhydration pathways to methionine biosynthesis, or whether the pathological effects of rhizobitoxine are due chiefly to inhibition of beta-cystathionase.

Journal Article↗