Dietary Methionine Intake Research Articles

Interaction between Dietary Methionine and Methyl Donor Intake on Rat Liver Betaine-homocysteine Methyltransferase Gene Expression and Organization of the Human Gene

We previously showed that rat liver betaine-homocysteine methyltransferase (BHMT) mRNA content and activity increased 4-fold when rats were fed a methionine-deficient diet containing adequate choline, compared with rats fed the same diet with control levels of methionine (Park, E. I., Renduchintala, M. S., and Garrow, T. A. (1997) J. Nutr. Biochem. 8, 541-545). A further 2-fold increase was observed in rats fed the methionine-deficient diet with supplemental betaine. The nutrition studies reported here were designed to determine whether other methyl donors would induce rat liver BHMT gene expression when added to a methionine-deficient diet and to define the relationship between the degree of methionine restriction and level of methyl donor intake on BHMT expression. Therefore, rats were fed amino acid-defined diets varying in methionine and methyl donor composition. The effect of diet on BHMT expression was evaluated using Northern, Western, and enzyme activity analyses. Similar to when betaine was added to a methionine-deficient diet, choline or sulfonium analogs of betaine induced BHMT expression. The diet-induced induction of hepatic BHMT activity was mediated by increases in the steady-state level of its mRNA and immunodetectable protein. Using methyl donor-free diets, we found that methionine restriction was required but alone not sufficient for the high induction of BHMT expression. Concomitant with methionine restriction, dietary methyl groups were required for high levels of BHMT induction, and a dose-dependent relationship was observed between methyl donor intake and BHMT induction. Furthermore, the severity of methionine restriction influenced the magnitude of BHMT induction. To study the molecular mechanisms that regulate the expression of BHMT, we have cloned the human BHMT gene. This gene spans about 20 kilobases of DNA and contains 8 exons and 7 introns. Using RNA isolated from human liver and hepatoma cells, a major transcriptional start site has been mapped using the 5' rapid amplification of cDNA ends technique, and this start site is 26 nucleotides downstream from a putative TATA box.

Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association.

Homocysteine is a sulfur-containing amino acid, rapidly oxidized in plasma to the disulfides homocystine and cysteine-homocysteine (Figure 1⇓). Plasma/serum total homocysteine, also termed homocyst(e)ine, is the sum of homocysteine in all 3 components. Figure 2⇓ displays factors involved in the metabolism of homocysteine, including its metabolic relationship to methionine. Although dietary intake of total protein and methionine does not correlate significantly with blood homocyst(e)ine,1 a single dose of oral methionine (100 mg/kg body weight) can elevate homocyst(e)ine levels, and as described further below, this has been used as a diagnostic test to detect disordered homocyst(e)ine metabolism. Because variable changes in homocyst(e)ine levels have been observed postprandially,2 it is customary to obtain measurements in the fasting state. Normal levels of fasting plasma homocyst(e)ine are considered to be between 5 and 15 μmol/L. Moderate, intermediate, and severe hyperhomocyst(e)inemia refer to concentrations between 16 and 30, between 31 and 100, and >100 μmol/L, respectively.3 Figure 1. Molecular species of homocysteine. Figure 2. Simplified outline of methionine/homocysteine metabolism. Vitamin coenzymes and substrates: THF, tetrahydrofolate; B2, riboflavin; B6, vitamin B6 as its biological active form, ie, pyridoxal 5′-phosphate; and B12, methyl cobalamin. Intermediate metabolite: DMG, dimethylglycine. Several vitamins function as cofactors and substrates in the metabolism of methionine and homocysteine (Figure 2⇑). Folic acid and cyanocobalamin (vitamin B12) regulate metabolic pathways catalyzed by the enzymes methylenetetrahydrofolate reductase (MTHFR) and methionine synthase, respectively, whereas pyridoxine (vitamin B6) is a cofactor for cystathionine β-synthase. A number of studies have shown inverse relationships of blood homocyst(e)ine concentrations with plasma/serum levels of folic acid, vitamin B6, and vitamin B12.4 5 6 Administration of supplemental folic acid in doses between 0.2 and 15 mg/d can lower plasma homocyst(e)ine levels without apparent toxicity.7 8 …

Dietary methionine intake effects on egg component yield, composition, functionality, and texture profile analysis

The influence of supplemental Met levels ranging from 413 to 556 mg per hen per d (mg/HD) on liquid egg component yield, composition, and functionality was examined in mature layers (29 wk of age). Egg weight, component yield, solids, and CP content of albumen and yolk were determined. Texture profile analysis, feed ingredient functionality testing, and PAGE were conducted to determine whether increased egg total solids and CP content resulted in altered egg component functionality or electrophoretic protein banding pattern. Albumen component yield increased significantly on a mass basis at 507 and 556 mg/HD Met compared to 413 mg/HD Met. Yolk mass yield was significantly increased at 556 mg/HD Met compared to 413 mg/HD Met. Consumption above 413 mg/HD Met resulted in significantly increased albumen total solids and protein. Yolk solids were not significantly different; however, yolk CP was significantly increased at 507 and 556 mg/HD Met compared to 413 mg/HD Met. Albumen and yolk functionality at 413 and 507 g/HD Met were not significantly different in relation to cake volume or height. Emulsion separation at 120 min was significantly increased for 556 mg/HD Met compared to 413 and 507 g/HD Met. There were no significant differences in hardness or springiness of albumen and yolk gel plugs and electrophoretic protein banding patterns. Increased understanding of the influence of Met on liquid egg yield and composition may provide the egg producer with an effective and advantageous management technique for shell egg production specifically managed to maximize liquid egg product.

Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies?

Results from experimental animals and other laboratory data have suggested a role for methionine, an essential amino acid, in normal closure of the neural tube. We hypothesized that women who had higher dietary intakes of methionine would be at lower risk for neural tube defect (NTD)-affected pregnancies. Data were derived from a population-based case-control study of fetuses and liveborn infants with NTDs among a 1989-1991 California birth cohort. Interviews, which included a 100-item food frequency questionnaire, were conducted with mothers of 424 NTD cases and 440 nonmalformed controls. Risk for having an NTD-affected pregnancy was estimated according to quartiles (established from intakes among control mothers) of average daily maternal dietary intake of methionine in the 3 months before conception. We observed an approximately 30-40% reduction in NTD-affected pregnancies among women whose average daily dietary intake of methionine was above the lowest quartile of intake (> 1,341.86 mg/ day). These reductions in NTD risk were observed for both anencephaly and spina bifida; remained after adjustment for maternal race/ethnicity and education; and were observed irrespective of maternal level of folate intake. Although we were unable to establish whether the observed reductions in NTD risk were attributable to maternal periconceptional methionine intake or to another highly correlated nutrient, these data add to the growing body of evidence that maternal diet plays a role in neural tube closure.

Is dietary intake of methionine associated with a reduction in risk for neural tube defect‐affected pregnancies?

Is dietary intake of methionine associated with a reduction in risk for neural tube defect‐affected pregnancies?

Effect of Dietary Methionine Intake on Egg Component Yield and Composition

The effects of methionine intake on liquid egg component yield and composition were examined in two laying hen experiments using diets supplemented with differing levels of methionine. In Experiment 1, a high methionine intake level of 512 was compared to 326 mg per hen-day (HD). The 512 mg/HD intake significantly increased egg weight, component mass, and total solids in both albumen and yolk. Experiment 2 examined methionine intakes of 328, 354, 392, and 423 mg/HD. There were no significant differences in egg weight, component yield, or egg production among the treatments. Albumen solids from the 423 mg/HD intake level were significantly elevated when compared to 328 and 354 mg/HD. A methionine consumption of 354 mg/HD resulted in significantly lower yolk solids than 328, 392, and 423 mg/HD. Methionine intakes of 392 and 423 mg/HD did result in significantly increased crude protein content of albumen and yolk compared to 328 and 354 mg/HD methionine. Experiment 1 found elevated dietary methionine increased egg size, component mass, and solids content of albumen and yolk. Experiment 2 methionine intake significantly increased crude protein of albumen and yolk without changes in egg size or component yield. These results indicate a methionine intake range that will alter liquid component composition while egg size remains unchanged.

Use of Barley in Laying Hen Diets

Two experiments were conducted to evaluate the performance of Leghorn hens fed two barley cultivars, Morex and Glenn (Experiment 1), and a high protein (Experiment 2) feed grade barley (HPB). In Experiment 1 isonitrogenous and isocaloric barley diets were formulated to replace 17, 33, 50, 67, 83, and 100% of corn and fed to hens from 20 through 36 wk of age. Egg production and egg weights from hens fed barley diets were similar and equivalent to those of hens on the corn diet. Values for feed utilization (FU) in grams of feed per gram egg mass for Morex barley, Glenn barley, and corn diets were 2.68, 2.64, and 2.36 and for feed consumption in grams of feed per day were 116.48, 115.26, and 106.23, respectively.In Experiment 2 the HPB diets were formulated to replace all corn with equivalent protein content (15% CP) and differences in ME content, lysine, and methionine levels. The HPB-soybean control diet (HPB-SBM) contained 6% tallow and 2,605 kcal ME/kg diet. These diets were fed to layers from 36 through 64 wk of age. Egg weights were significantly (P<.05) reduced by at least 1 g when dietary lysine was decreased from .72 to .68%, dietary methionine decreased from .32 to .29%, and ME decreased from 2,605 to 2,310 kcal ME/kg diet. Decreased egg weights from hens fed test barley diets did not significantly increase shell weight per unit surface area. The FU for the HPB-SBM diet containing added tallow was 2.38 compared with a value of 2.68 for the HPB diet without tallow. The reduction of dietary intakes of ME, lysine, and methionine significantly reduced (P<.05) body weight gains of layers from 36 to 64 wk of age.

Effects of methionine and other sulfur compounds on drug conjugations

Conjugation reactions in the detoxification of drugs and environmental chemicals occur with various sulfur-containing substances. These reactions include: (1) glutathione (GSH, reduced glutathione) conjugation with subsequent mercapturic acid synthesis; (2) sulfate conjugation (sulfate ester synthesis); (3) methylation by S-adenosylmethionine (SAM); (4) thiosulfate conjugation of the cyanide ion, resulting in thiocyanate synthesis; (5) chelation of toxic metals by metallothionein, a sulfhydryl-rich protein. Of the drug conjugation reactions affected by methionine and cysteine intake and metabolism, sulfate and glutathione reactions have the greatest physiological significance. Much study has been devoted to the determination of intraand extracellular concentrations and transport of sulfur-containing compounds, and their relation to xenobiotic metabolism. Studies of the influence of dietary sulfur amino acid intake on the utilization during xenobiotic metabolism of sulfur-containing compounds are more limited, however. This review describes these studies as they relate to sulfur amino acid nutrition and Phase II drug conjugations. The major focus is on the effect of dietary methionine and cysteine intake on sulfate and glutathione conjugation reactions.

Effects of low dietary intake of methionine, choline or proteins on the biotransformation of arsenite in the rabbit

The effects of 6 weeks feeding with diets low in methionine, choline, or proteins on the biotransforma- tion and retention of 76As-labelled arsenite (0.4 mg As/kg bw) in rabbits have been studied. All test diets caused a significant decrease in the urinary excretion of dimethyl[ 76As]-arsinic acid, the main metabolite of inorganic arsenic. This gave rise to an increased retention of arsenic in the tissues, especially liver and lung. The test diets also caused a specific increase of the arsenic concentration in liver microsomes. The results indicate that subjects with a poor nutritional status have a lower capacity of methylating and thereby detoxifying inorganic arsenic.

Effects of high dietary methionine on activities of selected enzymes in the liver of kittens ( felis domesticus)

1. 1. Growing male kittens were fed an 18% casein diet supplemented with 2, 3, or 4% l-methionine (MET) for 6 weeks. 2. 2. Free MET concentration in liver increased 30-fold and cystathionine two- to three-fold; the activity of adenosyl-MET transferase and cystathionase also increased but remained lower than previously found in rats. 3. 3. Taurine concentration in liver decreased in cats fed excess MET and appeared to depend on taurine intake. 4. 4. Alanine aminotransferase activity was high in all groups while serine dehydratase activity was very low. 5. 5. Pyruvate kinase and malic enzyme activities which are normally low in cat liver increased after excess MET. Also, glucose 6-phosphate and 6-phosphogluconate dehydrogenases increased. 6. 6. Cat liver metabolism showed limited adaptation to an excess dietary intake of methionine compared to that found in rats.

Regulation of hepatic betaine-homocysteine methyltransferase by dietary methionine

The hepatic activity of betaine-homocysteine methyltransferase is a complex function of the content of methionine in the diet. Enzyme levels are lower in the livers of rats fed a 0.3% methionine diet than in livers of animals maintained on either methionine-free or excessivemethionine (1.0%) rations. The finding that activities are increased at both extremes of the spectrum of dietary methionine intake suggests the possibility that the betaine-homocysteine methyltransferase reaction may function both to maintain tissue concentrations of methionine when intake of this amino acid is limited and to remove homocysteine when methionine intake is excessive.

The inhibitory action of L-dihydroxyphenylalanine (L-dopa) in the presence of a monoamine oxidase inhibitor on protein synthesis in vivo and the partial amelioration of this by methionine supplementation.

Male Wistar rats of various age groups were injected daily over a period of 3 weeks with iproniazid (10 micrograms/g body wt.) and L-dihydroxyphenylalanine (L-dopa; 0.1 mg/g body wt.). On the final day 1 h before the termination of the experiment the animals were injected with L-[14C]valine (0.1 microCi/g body wt.). The specific radioactivity of the valine in the proteins of the subcellular fractions of the tissues examined, relative to the time-integrated mean specific radioactivity of this amino acid in the acid-soluble pools of these tissues, was used to assess protein synthesis. The L-dopa/monoamine oxidase-inhibitor treatment was associated with 30--40% inhibition of protein synthesis. Supplementation of the dietary methionine intake by injection of this amino acid markedly diminished the inhibitory action of the L-dopa/monoamine oxidase-inhibitor treatment on protein synthesis in all fractions examined.

DETERMINATION OF THE METHIONINE REQUIREMENT OF GROWING PIGS USING SERUM FREE AMINO ACIDS

Six littermate Yorkshire gilts averaging 18 kg body weight were fed a semipurified diet containing six graded levels of methionine during six 4-day feeding periods in a Latin square design. Serum methionine concentrations were determined at the end of each period. Plotting serum methionine concentration against dietary methionine intake showed the methionine requirement to be 0.46% of the diet; this estimate was substantiated by animal performance data.

THE LIPOTROPIC ACTION OF COLD. 2. THE INFLUENCE OF COLD AND CHOLINE DEFICIENCY ON SERUM LIPIDS OF RATS AT DIFFERENT INTAKES OF DIETARY METHIONINE.

The effect of exposure of rats to cold for a 10-day period on the concentration of serum lipids in control and choline-deficient animals was studied at four dietary intakes of methionine. Changes in total lipids, total and free cholesterol, phospholipid, and triglyceride levels were measured.In control (choline-fed) animals, phospholipid, cholesterol, and the ratio of free:ester cholesterol levels were not altered by cold exposure, but a marked decrease (25–30%, P &lt; 0.01) in the levels of total serum lipids occurred. This was a result of a 45–70% decrease in triglyceride levels. The concentration of the triglyceride-rich low-density lipoproteins (Sf10–400) in the serum fell in the cold-exposed animals as indicated by lowered triglyceride:cholesterol ratios.Although cold exposure prevented fatty livers in choline-deficient rats at high methionine intakes, it did not prevent the characteristic decrease in serum lipids found in choline deficiency at any of the methionine intakes studied. Decreases in total lipids (20–40%), triglyceride (10–50%), cholesterol (15–40%), and phospholipids (15–40%) were found. It was concluded that the ability of cold exposure to overcome choline deficiency is limited, apparently, to the fatty liver syndrome and has no effect on the decreased serum lipid levels.

THE LIPOTROPIC ACTION OF COLD. I. THE INFLUENCE OF COLD AND CHOLINE DEFICIENCY ON LIVER LIPIDS OF RATS AT DIFFERENT INTAKES OF DIETARY METHIONINE.

The effect of cold exposure and choline deficiency on the levels of liver lipids of male albino rats was studied at four dietary intakes of methionine (20–100 mg per rat per day). After exposure of the animals to cold (2–3 °C) for a 10-day period, the liver lipids were analyzed for total and free cholesterol, phospholipid, and triglyceride.In choline-fed animals, cold exposure did not affect triglyceride or total cholesterol levels but elevated phospholipid and free cholesterol and decreased ester cholesterol. The increase in phospholipid levels occurred at all methionine intakes with the changes in the cholesterol fractions occurring only at methionine intakes &gt;40 mg per day.In choline-deficient rats, there was evidence that the lipotropic action of cold exposure was related to dietary methionine intake. At methionine intakes &lt;60 mg per rat per day, fatty infiltration of the livers of the choline-deficient cold-exposed rats occurred, as evidenced by the accumulation of triglyceride and ester cholesterol. Concomitantly, phospholipid levels decreased. The data suggest that cold increases the capacity of the animal to synthesize choline from endogenous sources.