Manipulating the sulfur amino acid content of the early diet and its implications for long-term health.
Epidemiological studies of human populations show that poor growth in utero predisposes an individual to the later development of type 2 (non-insulin-dependent) diabetes mellitus and hypertension in adulthood. This phenomenon is not confined to man; feeding pregnant rats diets moderately deficient in protein has a similar effect, programming the adult blood pressure and glucose metabolism of the offspring. A restriction in the amino acid supply was thought to cause poor fetal growth. However, recent experiments have shown that this is not the case and instead have implicated the metabolism of the S-containing amino acids. Many semi-synthetic experimental diets contain an imbalance in S-containing amino acids, forcing the animal to synthesise a sizeable part of its cysteine requirement from methionine. Unfortunately, when the diet is low in protein, the oxidation of amino acids is reduced, perturbing methionine metabolism and increasing levels of homocysteine. It is this interaction between protein content and composition of the diet which influences neonatal viability and may also determine the long-term health of the offspring. An excess of homocysteine is known to affect levels of two of the main mediators of cellular methylation reactions, S-adenosyl methionine and methylene tetrahydrofolate. S-adenosyl methionine is the methyl donor for the methylation of newly-synthesised DNA, regulating chromatin assembly and gene expression. The balance between S-adenosyl methionine and the methylated derivatives of folic acid may be critical for the development of differentiating cells and the long-term regulation of gene expression.
Rees
William D
WD
The Rowett Research Institute, Aberdeen, UK. wdr@rri.sari.ac.uk
D000603:Amino Acids, Sulfur / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000378:metabolism; D009751:Nutritional Requirements; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats
D000603:Amino Acids, Sulfur; D004044:Dietary Proteins; D006710:Homocysteine; D008715:Methionine