Soy induces phase II enzymes but does not inhibit dimethylbenz[a]anthracene-induced carcinogenesis in female rats.

Isoflavones in soy may play a role in the prevention of cancer through their capacity to affect antioxidant or protective phase II enzyme activities. This study evaluated the effects of dietary isoflavone levels on the induction of antioxidant and phase II enzyme activities and inhibition of breast carcinogenesis. Female Sprague-Dawley rats (36 d) were fed one of four purified diets with casein, or with soy containing three levels of isoflavonoids (0.03, 0.4 or 0.81 mg/g diet; low, middle and high level of isoflavones, respectively). After 2 wk, enzyme activity was determined of rats (n = 6-7) from each diet group. Liver glutathione peroxidase and glutathione reductase activities, blood glutathione levels, kidney glutathione S-transferase and colon quinone reductase (QR) activities were greater in rats consuming the high isoflavone diet compared to rats consuming the casein diet. Kidney QR and liver, kidney, small intestine, and colon UDP-glucuronosyltransferase activities were greater in rats fed the high isoflavone diet compared to rats fed the casein and low-isoflavone diets. Liver and blood oxidized glutathione were lower in rats fed the high-isoflavone diet compared to those fed the low-isoflavone diet. A subset of rats (n = 86) was fed the purified diets for 2 wk and intubated with dimethylbenz[a]anthracene or peanut oil and palpated weekly for tumors. At 13 wk, there was an inverse relationship (R(2) = 0.911, P < 0.09) between tumor incidence and increasing isoflavone intake. These data support the mechanism of soy and soy isoflavones as antioxidant and phase II enzyme inducers, but not as tumor inhibitors.     

Pancreatic response to long-term feeding of soy protein isolate, casein or egg white in rats

Rats were fed purified diets which provided 24% protein from casein (C), soy protein isolate (SPI), or egg white (EW) for 18 mo. Groups of rats were killed at 3, 6, 12 and 18 mo; the pancreata were removed and examined histologically for occurrence of atypical nodules. The weight, protein, DNA, trypsin and chymotrypsin concentrations of the pancreas at each period were measured. Over the entire experimental period, body weight did not differ among groups. Pancreatic weight, protein and trypsin activity were highest in the EW group, followed by the SPI group, and lowest in the C group. Chymotrypsin activity was significantly higher in the EW and SPI groups than the C group. DNA content did not differ significantly among groups over the entire experimental period, although it was elevated in the SPI or EW groups compared to the C groups at some of the time periods. Only one microscopic nodule was observed in all of the animals; it was found at 3 mo in the pancreas from an animal fed EW. Overall, the results suggest that the elevation in enzyme activity and pancreatic weight associated with long-term consumption of EW and SPI did not result in development of pancreatic lesions in rats.     

Soy protein reduces paraquat-induced oxidative stress in rats

The effect of soy protein, soy isoflavones and saponins on paraquat (PQ)-induced oxidative stress was investigated in rats. Rats were fed experimental diets containing casein (CAS), soy protein (SPI), and casein with soy isoflavones and saponins (CAS + IS). The diets were supplemented or not with 0.025% paraquat (CAS + PQ, SPI + PQ, and CAS + IS + PQ). The protective effects of soy protein, soy isoflavones, and saponins on paraquat-induced oxidative stress were examined. Ingestion of soy protein generally mitigated the lung enlargement (P = 0.076), loss of body weight (P = 0.051) and oxidation of liver lipid (P = 0.043) and glutathione (P = 0.035) induced by paraquat, although soy isoflavones and saponins did not. To determine whether soy protein exerted its antioxidative effects by preventing paraquat absorption from digestive organs, rats were fed CAS or SPI diets and orally administered a 12.5 g/L paraquat solution. Plasma, urine, and fecal paraquat concentrations did not differ between the two groups, indicating that soy protein did not prevent paraquat absorption. The present study suggests that intake of soy protein itself, but not soy isoflavones and saponins, reduces paraquat-induced oxidative stress in rats, although this effect was not due to reduced absorption of paraquat from digestive organs.     

Effects of ingestion of hibernia and Prudhoe Bay crude oils on hepatic and renal mixed function oxidase in nestling herring gulls (Larus argentatus)

Oral administration of Prudhoe Bay crude or Hibernia crude to nestling herring gulls increased the hepatic cytochrome P-450 content 4-fold. Concomitantly, there was an increase in various mixed-function oxidase and phase II enzyme activities. 7-Ethoxyresorufin O-deethylase was elevated 19-fold, benzo(a)pyrene 3-hydroxylase 6-fold, aniline hydroxylase 3-fold, and aminopyrine N-demethylase and uridine diphosphate glucuronyl transferase 2-fold. There was no change in reduced glutathione S-transferase activity. Renal mixed-function oxidase activities were also elevated. Herring gull livers contained very low levels of DT-diaphorase activity which was inducible 3- to 5-fold by oil administration.     

Consumption of soy protein isolate modulates the phosphorylation status of hepatic ATPase/ATP synthase beta protein and increases ATPase activity in rats

ATPase/ATP synthase plays important roles in the regulation of carbohydrate, protein, and lipid metabolism through modulating energy homeostasis. The purpose of this study was to examine the effects of feeding soy proteins and isoflavones (ISF) on the enzymatic activity and protein modification of hepatic mitochondrial ATPase/ATP synthase. In Expt. 1, Sprague-Dawley rats aged 50 d were fed diets containing either 20% casein or 20% alcohol-washed soy protein isolate (SPI) with or without supplemental ISF (770.7 micromol/kg diet) for 70 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without added ISF (154.1 micromol/kg diet) or 20% SPI for 90 d. Hepatic mitochondrial ATPase activity was significantly higher in the rats fed SPI than in those fed casein. Addition of ISF to SPI eliminated the action of SPI. ATPase/ATP synthase beta protein contents in the liver were unchanged; however, its patterns measured by 2-dimensional Western blot were different among dietary groups. The rats fed SPI or SPI plus ISF had 3 more major protein spots with the same molecular weights (80 kDa and 55 kDa) as those presented in the rats fed casein but with different isoelectric points. Pretreatment of hepatic mitochondrial proteins from the rats fed casein with alkaline phosphatase produced the same ATPase/ATP synthase beta patterns as observed in the SPI-fed rats and significantly elevated the ATPase activity. These results suggest that consumption of soy proteins increases hepatic ATPase activity, which might be a consequence of increased dephosphorylation or decreased phosphorylation of the mitochondrial ATPase/ATP synthase beta protein.     

Sodium 2-propenyl thiosulfate derived from garlic induces phase II detoxification enzymes in rat hepatoma H4IIE cells

There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is partly due to the organosulfur compounds in Allium vegetables and that these substances act through induction of phase II detoxification enzymes. Here, we hypothesized that alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS), and sodium 2-propenyl thiosulfate (2PTS), which were identified in onions and garlic, respectively, may induce phase II enzymes. Therefore, rat hepatoma cells (H4IIE) were cultured with 1 to 100 μmol/L of NPTS or 2PTS for 48 hours at 37°C; and the activities and messenger RNA (mRNA) expression levels of phase II enzymes in H4IIE cells were investigated. The effects of diallyl trisulfide and tert-butylhydroquinone, known as phase II inducers, were also examined as positive controls and compared with the responses of NPTS and 2PTS. Quinone reductase (QR) activity and mRNA expression levels of QR and epoxide hydrolase 1 were significantly increased by 2PTS (P < .05-.005). In particular, QR activity was increased at a relatively low concentration of 2PTS (10 μmol/L). However, glutathione S-transferase activity and mRNA expression levels of glutathione S-transferase A5 and uridine diphosphate glucuronosyl transferase 1A1 were not changed by 2PTS. In contrast, NPTS did not affect the activities and mRNA expression levels of these phase II enzymes. These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone.     

Intestinal zinc and carboxypeptidase A and B activity in response to consumption of test meals containing various proteins by rats

Rats were fed test meals containing 23% protein as casein (C), soy protein isolate (SPI) or egg white (EW) to assess effects of dietary protein sources on te amount of zinc and carboxypeptidase (CP, CPA, CPB) activity in the small intestinal contents. Groups of six rats each were killed at 1, 2.5 and 5 h postprandial and six rats fasted for 19 h served as a 0 time control. Consumption of a test meal increased the weight of small intestinal contents at 1 and 2.5 h compared with unfed animals and in a similar manner for all three protein sources. However, at various times during the postprandial period differences in the level of zinc and CP activity within the small intestinal contents among the three dietary protein sources were observed. Both the SPI and EW groups had significantly higher levels of CPA and CPB activity at 1 h postprandial than the C group. Only in the SPI group was the intestinal level of zinc increased at 1 and 2.5 h compared with the unfed group. At 1 and 2.5 h postprandial intestinal zinc was significantly higher in the SPI group than in the C and EW groups. The results indicate that the disappearance of zinc from the intestine is delayed in rats fed SPI, probably because of the presence of phytate.     

Effect of vitamin e on rat hepatic cytochrome p‐450 activity

Hepatic cytochrome P‐450 activity has been shown to be affected by various dietary factors including vitamin E. However, reports of the effect of dietary vitamin E on cytochrome P‐450 activity have been inconsistent. The aim of the present study was to investigate the influence of dietary vitamin E on rat hepatic cytochrome P‐450 activity. Three groups of six male weanling Sprague‐Dawley rats were fed semipurified diets containing 0, 100, or 1,500 ppm vitamin E for eight weeks. Vitamin E was given in the form of a‐tocopheryl acetate. Dietary vitamin E significantly affected liver vitamin E content (p < 0.05) but had no effect on rat hepatic total P‐450 content, N‐nitrosodimethylamine demethylase, and NADPH‐cytochrome‐P‐450 reductase activities. Hepatic pentoxyresorufin O‐dealkylase and glu‐tathione S‐transferase activities were significantly greater in rats fed 100 and 1,500 ppm vitamin E than in rats fed no vitamin E (p < 0.05). Dietary vitamin E induced changes in hepatic phospholipid fatty acid composition. Hepatic phos‐pholipid linoleate was significantly greater in rats fed 0 and 1,500 ppm vitamin E than in rats fed 100 ppm vitamin E (p < 0.05). Hepatic phospholipid eicosapentaenoate was increased significantly by dietary vitamin E (p< 0.05). Hepatic thiobarbituric acid‐reactive substance was significantly greater in rats fed no vitamin E than in rats fed 100 and 1,500 ppm vitamin E (p < 0.05). The results suggest that vitamin E may influence cytochrome P‐450 IIB1 enzyme activity and may affect hepatic phospholipid fatty acid composition.     

The influence of dietary protein on lipid peroxide formation in old, food restricted rats

The effect of deetary protein on in vivo lipid peroxidation in the liver and kidney of 21 months-old, SD male rats was investigated after feeding them isocaloric diets for 60 days. Rats were divided into four groups as 5% soy protein isolate (SPI), 20% SPI, 5% casein and 20% casein diet groups and they all received 15 g food/day (59 kcal/day or 25% food restriction). The liver and kidney SOD activities, as well as thiobarbituric acid-reactive substances (TBARS), were increased in low protein fed animals. Catalase activities did not have significant differences between groups, but it was 15 times higher in the liver than the kidney. Glutathione peroxidase (GPx) showed increased activities in the liver of animals fed 5% protein diet, but the same was not observed in the kidney. Total glutathione was higher in the organs of animals fed 20% protein diet rather than 5% protein diet for both organs, liver and kidney, and values of the former were much higher than those of the latter. Though enzyme activities were not altered as a function of dietary protein level of quality, there is a strong evidence that TBARS is somehow augmented by feeding a low protein diet.     

Effect of feeding peptic digest of soy protein isolate on rat serum cholesterol

Growing rats were fed ad libitum soy protein isolate (SPI) or its peptic (SPI-P) or tryptic digest (SPI-T) for a month and their sera were examined for cholesterol and triglyceride levels and enzyme activities such as cholinesterase, glutamate-pyruvate transaminase (GPT) and alkaline phosphatase. The rats fed SPI-P or SPI-T were inferior in growth to those fed SPI. Similarly, the serum glyceride level was lower in the SPI-P and SPI-T groups than in the SPI group. On the other hand, a significant difference was found in the serum cholesterol level between the SPI-P and SPI or SPI-T groups but not between the SPI and SPI-T groups. A similar tendency was observed for serum GPT and alkaline phosphatase activities, although there were no significant differences among dietary groups in small intestinal enzyme activities. As for the atherogenic index being a risk factor inducing atherosclerosis, the order of its value was SPI-P less than SPI less than SPI-T.     

The effect of soy protein isolate in the diet on retention by the rat of iron from radiolabeled test meals

The influence of soy protein isolate (SPI) in the diet on whole-body retention of extrinsically radiolabeled iron from test meals containing or not containing SPI was evaluated in marginally iron-deficient weanling rats. In experiment 1 SPI was compared with casein in a 2 X 2 factorial design: diets and test meals were either SPI-based or casein-based. Diets were fed for 13 days prior to the test meal and for 7 days subsequent to the test meal. Rats fed the SPI-based diet retained less iron from test meals than did rats fed the casein-based diet (66.1 vs. 74.8%, P less than 0.01). Experiment 2 showed that an SPI-based diet fed during the final 4 days of a 14-day pre-test meal period and subsequent to the test meal led to less iron retention compared to a casein-based diet. In addition to the observed diet effect, experiment 1 showed that iron retention was less from an SPI-based test meal than from a casein-based test meal, confirming previous reports of adverse effects of SPI on iron retention. The present experiments show that SPI can adversely affect from retention in two ways: by its presence in the diet before and after a test meal, and by its presence in a test meal.     

Effects of dietary lipid saturation on prolactin secretion, carcinogen metabolism and mammary carcinogenesis in rats

Isoenergetic diets containing 20% corn oil, 20% beef tallow, or an equal mixture of 10% corn oil and 10% beef tallow (mixed fat) were fed to 30 rats per diet for 28 weeks following weaning. DMBA [7,12-dimethylbenz(a)anthracene] was administered (1.75 mg/100 g body weight) in a single oral dose after 4 weeks of feeding. After 28 weeks, 70% of the rats fed corn oil had mammary tumors versus 47% for mixed fat and 30% for tallow. Diet had no effect on the number of tumors per tumor-bearing rat or the proportion of tumors that were adenocarcinomas. Other rats assigned to each of the three diets were killed at the time corresponding to DMBA administration for examination of hepatic mixed-function oxidase activity. NADPH cytochrome c reductase activity and cytochrome P-450 content were higher in rats fed corn oil or mixed fat rather than tallow. However, no significant differences in aryl hydrocarbon hydroxylase, glutathione transferase, and uridine-diphosphoglucuronide transferase activities were observed. The effects of dietary fat saturation on enzyme activity failed to show a clear association with DMBA carcinogenesis. In other rats assigned to the three dietary treatments for 4 or 16 weeks, lipid saturation did not change serum prolactin (PRL) concentrations during diestrus or proestrus. PRL secretion was examined following a provocative stimulus (perphenazine) in rats fed the experimental diets for 4 or 10-22 weeks. Although perphenazine increased serum PRL and depleted the pituitary of PRL, differences in dietary lipid saturation caused no significant changes in these indices. These data show that the incidence of mammary tumors in rats fed high fat diets (20% by weight) was greater in those fed corn oil compared to beef tallow. The effect of dietary lipid source on tumorigenesis was not associated with changes in carcinogen-metabolizing enzyme activity or PRL secretion.     

Aqueous ethanol extraction of dietary soy protein isolate improves 59Fe absorption by the rat from a casein-based test meal

A commercial soy protein isolate (SPI) was further processed in an attempt to understand how a diet based on SPI can cause decreased iron retention by the rat from a separately administered casein-based test meal. Groups of eight rats were fed either a casein-based diet or a diet based on SPI. The acid-precipitated SPI was incorporated into diets as such, after neutralization, after 60% (v/v) ethanol extraction and neutralization, or after 60% ethanol exposure and neutralization. All dietary SPI was heat-treated by exposure to steam at 108 degrees C for 30 min. Rats were fed their respective diets, each containing 25 mg Fe/kg, for 13 d, and then all rats were fed a 59Fe-radiolabeled 2.5-g casein test meal containing 64 micrograms of iron. Ingested radioactivity was determined following the meal, and retained radioactivity over the subsequent 10-d period. Absorption was not distinguishable for groups fed the casein-based (78.3 +/- 3.6%) and the ethanol-extracted, SPI-based diet (80.2 +/- 5.4%). Absorption was lower (P less than 0.01) for groups fed each of the other SPI-based diets: SPI as such (68.3 +/- 8.9%), neutralized SPI (69.8 +/- 5.0%) and ethanol-exposed SPI (67.6 +/- 4.8%). An ethanol-extractable component of SPI may be responsible for decreased iron absorption by animals fed SPI prior to a radiolabeled test meal.     

Soy protein isolate enhances hepatic copper accumulation and cell damage in LEC rats

In a series of experiments, the effects of soy protein isolate (SPI), defatted soy (DFS) or SPI supplemented with L-methionine (SPIM) were examined in the Long-Evans rat with a cinnamon coat color (LEC rat), a model animal of Wilson's disease with a hereditary defect in the Atp7b gene resulting in defective copper metabolism and copper accumulation in hepatocytes. Milk casein in the control AIN-93G diet (20 g/100 g) was totally or 60% replaced by the soy products, SPI, DFS or SPIM (L-Met added to be equal to that in the control diet) beginning when rats were 6 wk old. Copper and iron concentrations in SPI and DFS were measured and the concentrations of these metals in the salt mix were adjusted so that test and the control diets had the same final concentrations. Food intake did not differ among groups. Rats were euthanized when they became moribund with jaundice. Survival time in the SPI diet group was shorter (14.0 +/- 0.8 wk) than in the control group (19.1 +/- 1.7 wk) (P < 0.001), and that in the DFS diet group was intermediate (16.0 +/- 1.7 wk). Survival time in the SPIM diet group did not differ from that of the SPI diet group. Copper concentrations in the livers of rats in the SPI and SPIM diet groups were approximately 80% higher than in rats fed the control diet. Liver iron concentrations did not differ among the groups. The results, including histological analyses, indicate that SPI enhances copper uptake into the liver cells and promotes liver cell damage in LEC rats. However, this did not occur in the livers of F344 rats with wild-type Atp7b. Recommendations to individuals suffering from Wilson's disease to avoid consuming soy protein may be warranted.     

Dietary soy protein isolate modifies hepatic retinoic acid receptor-beta proteins and inhibits their DNA binding activity in rats

Retinoic acid receptors (RAR) belong to the same nuclear receptor superfamily as thyroid hormone receptors (TR) that were previously shown to be modulated by dietary soy protein isolate (SPI). This study has examined the effect of dietary SPI and isoflavones (ISF) on hepatic RAR gene expression and DNA binding activity. In Expt. 1, Sprague-Dawley rats were fed diets containing 20% casein or 20% alcohol-washed SPI in the absence or presence of increasing amounts of ISF (5-1250 mg/kg diet) for 70, 190, or 310 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without supplemental ISF (50 mg/kg diet) or increasing amounts of alcohol-washed SPI (5, 10, and 20%) for 90 d. Intake of soy proteins significantly elevated hepatic RARbeta2 protein content dose-dependently compared with a casein diet, whereas supplemental ISF had no consistent effect. Neither RARbeta protein in the other tissues measured nor the other RAR (RARalpha and RARgamma) in the liver were affected by dietary SPI, indicating a tissue and isoform-specific effect of SPI. RARbeta2 mRNA abundances were not different between dietary groups except that its expression was markedly suppressed in male rats fed SPI for 310 d. DNA binding activity of nuclear RARbeta was significantly attenuated and the isoelectric points of RARbeta2 were shifted by dietary SPI. Overall, these results show for the first time, to our knowledge, that dietary soy proteins affect hepatic RARbeta2 protein content and RARbeta DNA binding activity, which may contribute to the suppression of retinoid-induced hypertriglyceridemia by SPI as reported.     

Effect of cholesterol supplementation on plasma and liver cholesteryl ester fatty acids in rats fed casein or soy protein

The effect of supplementation with cholesterol on plasma and liver cholesteryl ester fatty acids was examined in rats fed diets containing different protein sources. Weanling male rats were fed a semi-purified diet containing 20% casein or 20% soy protein for seven weeks and then 1% (by weight) of cholesterol was added for three more weeks. Rats fed soy protein grew consistently slower than those fed casein. The plasma and liver cholesterol contents were not significantly different between the two protein groups in the unsupplemented rats; however, they were significantly increased in cholesterol-fed animals, particularly in casein-fed rats. Analysis of the cholesteryl ester fatty acid composition in plasma and liver demonstrated that cholesterol-feeding significantly increased the levels of saturated fatty acids, monounsaturated fatty acids and linoleic acid in casein-fed rats as compared to those fed soy protein. The level of cholesteryl arachidonate in liver, which was low initially, increased slightly in the liver of casein-fed rats but did not significantly change in the plasma of either protein group.     

Effects of iron status and soy protein on iron absorption by rats

The effects of iron nutrition and soy protein on iron absorption by rats was studied. Rats were fed semipurified diets containing either 0, 5, or 20 micrograms of added iron per gram of diet to obtain groups with different iron status. After 3 weeks the rats had mean hemoglobin concentrations of 7.0, 10.7 and 13.2 g/dl, respectively. As the rats became more anemic, percent iron absorption from casein and soy protein diets increased. The relative availability of iron from soy compared with casein-based diets was 70 to 90%. Iron status did not affect the relative iron availability among treatments. The rat trials did not indicate any significant differences between iron absorption from meals containing soy flour (SF), soy protein concentrate (SC) or soy protein isolate (SI) regardless of the iron status of the rat. These studies do not support the hypothesis that the subject's iron status will affect the relative availability of iron from foods. Recent human iron absorption studies suggest that relative iron availability from meals containing soy proteins is lower than expected based on rat studies. Furthermore, differences in iron availability between soy flour and soy isolate observed in human studies are not apparent in these rat studies.     

Soy protein isolate and protection against cancer

OBJECTIVE: Results from epidemiological and animal studies suggest that consuming soy-containing diets reduces the incidence of certain cancers. The purpose of this presentation was to evaluate the potential of soy protein to prevent occurrence of prostate, breast and colon cancer. METHODS: Meta-analyses of published epidemiologic studies associating cancer risk with soy intake were performed. The incidence of chemically-induced mammary or colon tumors was determined for rats fed AIN-93G diets made with either casein or soy protein isolate (SPI). Western and Northern blot and microarray analyses were performed on rat mammary and colon tissues to study mechanisms underlying the effects of soy. RESULTS: Meta-analyses revealed reductions in the mean overall risk estimate for mammary (0.78, p < 0.001), colon (0.70, p < 0.001) and prostate (0.66, p < 0.001) cancer for soy consumers. The incidence of AOM-induced colon tumors and DMBA-induced mammary tumors was reduced (p < 0.05) in rats fed SPI-containing diets. Lower incidence of mammary tumors in SPI-fed rats was associated with: 1) reduced terminal end bud numbers (p < 0.05), 2) lower expression of the phase I enzyme CYP1B1 (p < 0.05) and 3) reduced expression of the Ah Receptor and ARNT (p < 0.05). CONCLUSIONS: SPI may protect against cancer via multiple mechanisms, including: 1) increased mammary gland differentiation, 2) decreased activation of procarcinogens to carcinogens and 3) regulation of genes in signal transduction pathways underlying tumor initiation, promotion and/or progression.     

Effect of dietary protein on the peroxidation of eicosapentaenoic acid in stroke-prone spontaneously hypertensive rats.

In order to investigate the effect of dietary EPA on liver GSH peroxidase (GSH-Px) activity in rats, highly concentrated EPA (78% ethyl ester form) was administrated to SHRSP (Stroke-prone spontaneously hypertensive rat) that were fed a casein, SPI (soybean protein isolate) or SPI diet with methionine for 4 weeks. The content of liver GSH in rats fed SPI was lower than that of rats fed the casein diet. Although no significant difference of liver GSH-Px was observed in rats after EPA supplement, a decrease of liver GSH-Px activity was found in rats fed the SPI diet when compared with rats fed the casein diet. The changes of liver GSH content and GSH-Px activity in rats fed SPI were found to be associated with methionine supplement. Addition of methionine to the SPI diet resulted in an increase of liver GSH content and GSH-Px activity. In addition, liver lipid peroxide concentration was increased in rats fed the SPI diet after EPA treatment. In contrast, EPA administered rats fed the SPI diet containing methionine showed a lower liver lipid peroxide concentration. These results suggest that methionine may play an important role in regulation of the utilization of EPA in SHRSP when fed a SPI diet.     

Phenylethanolamine-N-Methyl transferase may control methionine demethylation

Rats fed diets which contained 15% of casein and 0.620% of methionine with 0.0002, 0.02 and 0.42% of dietary inorganic sulfate had a dietary sulfate-related change in methionine metabolism. Rats fed the diets low in sulfate (0.0002%) had a 35% increase in methionine metabolism compared to rats fed the diets high in sulfate (0.42%). In contrast, rats fed the diet low in sulfate (0.0002%) had the lowest level of tissue S-adenosyl-methionine and the highest activity of phenylethanolamine-N-methyltransferase activity. Those animals fed the diet normal with respect to sulfate (0.02%) had intermediate levels of S-adenosylmethionine and phenylethanolamine-N-methyl transferase activity. Rats fed the diet high in sulfate (0.42%) had the highest level of tissue S-adenosyl-methionine and the lowest phenylethanol-amine-N-methyl transferase activity. Due to the inverse relationship between S-adenosylmethionine and phenylethanolamine-N-methyl transferase activity, it appears that the catecholamines may function as a methyl sink for the increase in the metabolism of methionine required to provide sulfate for rats fed diets low in sulfate.