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Nitrogen retention in men fed isolated soybean protein supplemented with L-methionine, D-methionine, N-acetyl-L-methionine, or inorganic sulfate.

The ability of various sulfur-containing compounds to replace L-methionine (L-Met) was investigated by metabolic balance studies in man. N-acetyl-L-Methionine (AcMet), D-methionine (D-Met), and sodium sulfate (Na2SO4) were used to supplement a diet deficient in sulfur amino acids. The daily diet contained 4.5 g nitrogen (N) from isolated soybean protein (SB) and 4.5 g from glycine and alanine (9 g total N). SB diet was given alone or supplemented to six adult men for periods of 9 days after a standardization period with an equal N eggwhite diet, preceded by a 2-day zero N adaptation period. Supplements provided equivalent amounts of sulfur to that present in 420 ml L-Met, the amount added to SB to bring the total sulfur amino acid content to 900 mg/day. AcMet was as benfeficial as L-Met in improving N balance but D-Met was not as effective as L-Met. Difference between balances obtained with L-Met and Na2SO4 was not significant due to large variation in response to Na2SO4. While addition of D-Met to SB did not result in significantly greater N retention than unsupplemented SB, NA2SO4 addition did cause increased N retention.

Adult↗

Occurrence of methionine-enkephalin-Arg6-Gly7-Leu8 with methionine-enkephalin, leucine-enkephalin and methionine-enkephalin-Arg6-Phe7 in human gastric antrum.

Recent studies on the nucleotide sequence of cloned DNA complementary to mRNA for preproenkephalin from bovine adrenal medulla and human pheochromocytoma have revealed that this precursor molecule contains four copies of methionine-enkephalin (Met-Enk) and one copy each of leucine-enkephalin (Leu-Enk), methionine-enkephalin-Arg6-Gly7-Leu8 (Met-Enk-Arg6-Gly7-Leu8) and methionine-enkephalin-Arg6-Phe7 (Met-Enk-Arg6-Phe7). We have demonstrated the existence of Met-Enk-Arg6-Gly7-Leu8 together with Met-Enk, Leu-Enk and Met-Enk-Arg6-Phe7 in human gastric antrum, using high performance liquid chromatography (HPLC) coupled with radioimmunoassays for these opioid peptides. The ratio of molar concentrations of these peptides in human gastric antrum is similar to the ratio of these peptides contained in preproenkephalin. Furthermore, gel filtration studies on Sephadex G-50 showed that most of immunoreactivities of these peptides were eluted at the elution position of each synthetic peptide without any detectable immunoreactivities at high molecular weight positions. These results indicate the presence of Met-Enk-Arg6-Gly7-Leu8 together with Met-Enk, Leu-Enk and Met-Enk-Arg6-Phe7 in human gastric antrum and further suggest that these opioid peptides are derived from the same preproenkephalin as that in the adrenal medulla and that the processing of preproenkephalin is almost complete in the gut.

Adult↗

Demonstration and characterization of immunoreactive methionine-enkephalin, leucine-enkephalin, methionine-enkephalin-Arg6-Gly7-Leu8 and methionine-enkephalin-Arg6-Phe7 in human phaeochromocytoma.

To elucidate whether or not human phaeochromocytoma contains methionine-enkephalin-Arg6-Gly7-Leu8 (Met-enkephalin-Arg-Gly-Leu) and methionine-enkephalin-Arg6-Phe7 (Met-enkephalin-Arg-Phe) together with methionine-enkephalin (Met-enkephalin) and leucine-enkephalin (Leu-enkephalin), all of which are known to exist in the same precursor molecule (preproenkephalin A), we examined extracts from 16 phaeochromocytomas using high performance liquid chromatography (HPLC) and gel exclusion chromatography coupled with radioimmunoassays (RIAs) for these four opioid peptides. Met-enkephalin-Arg-Gly-Leu-like immunoreactivity (-LI) and Met-enkephalin-Arg-Phe-LI existed together with Met-enkephalin-LI and Leu-enkephalin-LI in 16 phaeochromocytomas. There was a wide variation in contents of Met-enkephalin-LI, Leu-enkephalin-LI, Met-enkephalin-Arg-Gly-Leu-LI and Met-enkephalin-Arg-Phe-LI. Significant positive correlations were observed among the contents of these four opioid peptides in 16 phaeochromocytomas. HPLC and gel exclusion chromatography followed by the RIAs showed the presence of Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu and Met-enkephalin-Arg-Phe together with their high molecular weight forms, which existed in variable amounts. Molar ratios of the contents of these four opioid peptides determined after HPLC varies from case to case. These results indicate the co-existence of Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu and Met-enkephalin-Arg-Phe in human phaeochromocytomas, suggesting the preservation of amino acid sequences of these four opioid peptides even in neoplastic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy of DL-methionine hydroxy analog free acid and DL-methionine as methionine sources for pigs.

Two experiments were conducted to evaluate the efficacy of dietary DL-methionine hydroxy analog-free acid (MHA-FA, 88%) compared with DL-methionine (DLM, 99%) as Met sources in pigs. In Exp. 1, a total of 245 crossbred pigs (initial BW of 6.4 kg [SD = 0.5]) were allotted to 7 treatments in 7 replicates for an experimental period of 28 d. The basal diet (BD) was formulated to contain 17.5% CP and 0.21% Met. Dietary treatments included 1) BD, 2) BD + 0.030% DLM, 3) BD + 0.060% DLM, 4) BD + 0.090% DLM, 5) BD + 0.034% MHA-FA, 6) BD + 0.068% MHA-FA, and 7) BD + 0.103% MHA-FA; the MHA-FA was supplemented on an equimolar basis to the DLM. Because of a nonlinear response, exponential regression analysis was used to evaluate the responses, and a comparison of the equations was then made to determine the relative effectiveness of the 2 Met sources. With increases in dietary Met, weight gain increased (P < 0.05). Compared with DLM on a product-to-product (wt/wt) basis, the relative effectiveness of MHA-FA was calculated to be 73% for increasing weight gain and 54% for decreasing the feed:gain. In Exp. 2, a total of 30 weanling barrows [initial BW of 16.8 kg (SD = 2.8)] were used in a metabolism study to evaluate the relative value of MHA-FA to DLM. The BD was formulated to contain 16.9% CP and 0.21% Met. Dietary treatments included 1) BD, 2) BD + 0.030% DLM, 3) BD + 0.060% DLM, 4) BD + 0.046% MHA-FA, and 5) BD + 0.092% MHA-FA; the MHA-FA levels were chosen based on a pre-experiment estimate of bioequivalence in an attempt to provide approximately equal pig responses. There was no difference in fecal N output among the treatments; however, urine N linearly decreased with increasing concentrations of both sources (P = 0.034 for DLM, and P = 0.007 for MHA-FA), which resulted in a linear increase in retained N for both DLM (P = 0.012) and MHA-FA (P = 0.005). In addition, N retention (% of intake) linearly increased with increasing level of DLM (P = 0.014) and MHA-FA (P = 0.007). Using a slope-ratio procedure for comparison of the responses from the 2 sources, the relative biological equivalence value of MHA-FA to DLM in this experiment was 64.2% based on percent N retention and 66.3% based on the grams of N retained per day. Based on the results from both experiments, these data indicated that the mean relative bioequivalence of MHA-FA to DLM was 64% on a product-to-product (wt/wt) basis or 73% on an equimolar basis.

Animal Feed↗

Influence of methionine derivatives on effluent flow of methionine from continuous culture of ruminal bacteria.

Two separate studies were conducted using a continuous culture fermenter system to determine effects of supplementing D,L-methionine and various methionine derivatives on degradation of methionine by ruminal bacteria. A basal diet containing 20% alfalfa hay, 20% corn silage and 60% grain mix (DM basis) was provided at a rate of 75 g DM/d per fermenter and served as an unsupplemented control in both experiments. In Exp. 1, methionine sources included D,L-methionine, D,L-methionine hydantoic acid, D,L-methionine hydantoin, N-acetyl-D,L-methionine, methylthio-isobutyric acid, methylthio-propionic acid and D,L-methionine sulfoxide. These sources were added directly to fermenters twice daily and supplied an equivalent of 98 mg/d D,L-methionine (.13% of diet DM) and 21 mg/d S. Effluent methionine flow from fermenters was higher (P less than .05) with diets supplemented with D,L-methionine hydantoic acid (245 mg/d), D,L-methionine hydantoin (245 mg/d) and N-acetyl-D,L-methionine (270 mg/d) than with control (211 mg/d) or D,L-methionine (211 mg/d) treatments, indicating a lower ruminal bacterial degradation of these methionine derivatives. There were no major effects on bacterial fermentation due to methionine supplementation or source. In Exp. 2, methionine sources included D,L-methionine, methionine hydroxy analog and N-hydroxymethyl-D,L-methionine; these were mixed with the basal diet to provide an equivalent of 250 mg/d D,L-methionine (.33% of diet DM). Sodium sulfate was added to the control diet to attain equal S (54 mg/d) levels across treatments. Flow of methionine was not affected (P greater than .05) by methionine supplementation, indicating extensive degradation of all three methionine sources by ruminal bacteria.

Animals↗

Effects of excess dietary l-methionine and N-acetyl-l-methionine on growing rats.

We have determined the effects of excessive dietary intakes of L-methionine and N-acetyl-L-methionine by measuring parameters which are known to be affected by excess methionine. Male Sprague-Dawley weanling rats were fed complete diets containing 10% protein supplied as isolated soybean protein and graded levels of supplemental L-methionine (from 0.30% to 5.0%) or equimolar levels of N-acetyl-L-methionine. The basal diet without supplemental methionine contained 0.15% methionine. Rats fed diets containing 0.3% supplemental L-methionine or the equivalent levels of supplemental N-acetyl-L-methionine grew best. Higher dietary levels of either L-methionine or N-acetyl-L-methionine caused progressive decreases in weight gain. However, L-methionine at 1.8% and above tended to more severely depress growth than did equivalent amounts of N-acetyl-L-methionine. L-Methionine at levels of 1.2% and above, or equivalent levels of N-acetyl-L-methionine caused comparable hypertrophy of the spleen and comparable increases in spleen iron levels. Hematocrits were not affected by either L-methionine or N-acetyl-L-methionine at the levels used in this experiment. We have concluded that N-acetyl-L-methionine is no more detrimental than L-methionine and is less detrimental at very high levels as evidenced by weight gain.

Animals↗

The use of low protein liquid diets to determine the methionine requirement and the efficacy of methionine hydroxy analogue for the three-week-old pig.

A mechanical feeding device that dispenses liquid diets hourly was developed to feed 3-week-old pigs under carefully controlled and sanitary conditions. Pigs were weaned at 19-21 days of age, placed in individual cages of the automatic feeder, and trained to eat low protein (9%) milk diets, which were supplemented with essential amino acids, glutamic acid and monosodium glutamate so as to be equivalent to 14% protein nitrogen. The basal 9% protein diet contained 0.25% L-methionine and 0.08% L-cysteine and was supplemented with L- or DL-methionine or DL-methionine hydroxy analogue (MHA) at various levels for evaluation of the methionine requirement. Pigs fed the basal diet showed a significant decrease in gain, feed efficiency and plasma urea (P less than 0.05) relative to animals that received supplemental methionine or MHA. The plasma methionine concentration remained below 0.2 mumol/ml plasma when pigs were fed diets containing 0.25-0.51% methionine; however, a significant increase in plasma methionine (P less than 0.05) was seen when pigs were fed diets that contained greater than 0.51% methionine activity in the form of L- or DL-methionine or DL-MHA. The highest average daily gain (470 g) obtained with a diet containing 0.51% methionine was significantly better (P less than 0.05) than diets containing more or less L- or DL-methionine, and the feed efficiency of this diet (1.58 kg feed per kilogram gain) was also significantly better (P less than 0.05) than the feed efficiency obtained with other dietary methionine levels. MHA (0.17%) added to the basal diet significantly improved the average daily gain (P less than 0.05) and lead to a significant decrease in plasma urea (P less than 0.05) relative to pigs that received the basal diet. Supplemental MHA (greater than 0.51% methionine level) produced significant increases (P less than 0.05) in plasma methionine. These data show that the methionine requirement of the 3-week-old pig can be satisfied with L- or DL-methionine or DL-MHA at a level equal to 0.51% of the dietary solids and that these three are equivalent. These experiments also show that low protein diets supplemented with amino acids can be used for liquid feeding of pigs weaned at 3 weeks of age, and average daily gains of greater than 400 g can be realized.

Amino Acids↗

Metabolism of DL-methionine and methionine analogs by rumen microorganisms.

Rates of degradation of DL-methionine and a number of methionine derivatives by rumen microorganisms were studied in vitro. Methionine hydroxy analog, the ammonium salt, and the amide derivative of methionine hydroxy analog were degraded more slowly than was methionine. Methyl and ethyl esters of methionine hydroxy analog were rapidly converted to methionine hydroxy analog, which was then degraded. Whole rumen contents were separated into protozoal and bacterial fractions, and rates of disappearance of [14C]carboxyl-labeled methionine and methionine hydroxy analog were determined. Disappearance of the label tended to be slower in the bacterial fraction; however, incorporation into cellular material tended to be higher for the bacterial than for the protozoal fraction. Disappearance of labeled methionine hydroxy analog was slower than labeled methionine in all fractions. Addition of unlabeled methionine inhibited disappearance of labeled methionine hydroxy analog, but unlabeled methionine hydroxy analog did not affect disappearance of labeled methionine. The effect of either Na2SO4, methionine, or methionine hydroxy analog on neutral detergent fiber digestion was related to amount of sulfur in the medium and not source of sulfur.

Animals↗

Preoperative methionine loading enhances restoration of the cobalamin-dependent enzyme methionine synthase after nitrous oxide anesthesia.

BACKGROUND: Prolonged exposure to nitrous oxide causes adverse effects mimicking those of cobalamin deficiency. This is explained by irreversible oxidation of cobalamin bound to the enzyme methionine synthase. The inactivation of methionine synthase by nitrous oxide in cultured human fibroblasts is decreased at high concentrations of methionine in culture medium. METHODS: We investigated the possible protection against cobalamin inactivation by preoperative methionine loading in patients undergoing nitrous oxide anesthesia. Fourteen patients receiving anesthesia for 75-230 min were included. Half of these patients received a peroral methionine loading dose 2 h before anesthesia. RESULTS: After nitrous oxide exposure, a considerable inactivation of methionine synthase in mononuclear white blood cells was seen in all patients, reaching a nadir after 5-48 h. In the patients not subjected to a methionine load, recovery of enzyme activity was not complete within 7 days. In the patients receiving a methionine load, the kinetics of inactivation of methionine synthase were similar, but the rate and extent of enzyme recovery was higher than in patients not receiving methionine, and in four patients, the enzyme activity even exceeded the preoperative level. The inactivation of methionine synthase was associated with a transient increase in plasma homocysteine, and the homocysteine concentration was still increased (mean 28.7%) 7 days after anesthesia in the patients not receiving methionine. A marked peak in homocysteine concentration was observed immediately after anesthesia in the methionine-loaded patients, but the homocysteine level was still increased (mean of 30.5%) after 7 days. The activity of the other cobalamin-dependent enzyme, methylmalonyl coenzyme A mutase, in the mononuclear white blood cells, and the serum concentration of the cobalamin marker methylmalonic acid, were not altered after nitrous oxide anesthesia or methionine loading or both. CONCLUSIONS: Our data suggest that short time exposure to nitrous oxide selectively impairs the function of the cobalamin-dependent methionine synthase. Furthermore, preoperative administration of methionine should be considered as a means to counteract adverse effects of nitrous oxide.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

An essential role of s-adenosyl-L-methionine:L-methionine s-methyltransferase in selenium volatilization by plants. Methylation of selenomethionine to selenium-methyl-L-selenium- methionine, the precursor of volatile selenium.

Selenium (Se) phytovolatilization, the process by which plants metabolize various inorganic or organic species of Se (e.g. selenate, selenite, and Se-methionine [Met]) into gaseous Se forms (e.g. dimethylselenide), is a potentially important means of removing Se from contaminated environments. Before attempting to genetically enhance the efficiency of Se phytovolatilization, it is essential to elucidate the enzymatic pathway involved and to identify its rate-limiting steps. The present research tested the hypothesis that S-adenosyl-L-Met:L-Met S-methyltransferase (MMT) is the enzyme responsible for the methylation of Se-Met to Se-methyl Se-Met (SeMM). To this end, we identified and characterized an Arabidopsis T-DNA mutant knockout for MMT. The lack of MMT in the Arabidopsis T-DNA mutant plant resulted in an almost complete loss in its capacity for Se volatilization. Using chemical complementation with SeMM, the presumed enzymatic product of MMT, we restored the capacity of the MMT mutant to produce volatile Se. Overexpressing MMT from Arabidopsis in Escherichia coli, which is not known to have MMT activity, produced up to 10 times more volatile Se than the untransformed strain when both were supplied with Se-Met. Thus, our results provide in vivo evidence that MMT is the key enzyme catalyzing the methylation of Se-Met to SeMM.

Adaptation, Physiological↗

Comparative metabolism of L-methionine and N-acetylated derivatives of methionine.

These experiments compared the metabolism of the N-acetylated derivatives of D- or L-methionine to that of L-methionine. Spargue-Dawley rats were orally or intraperitoneally dosed with N-[1-14C]acetyl-L-methionine, N-[1-14C]acetyl-D-methionine, or sodium [1-14C]acetate. 14CO2 was collected at intervals over 24 hours. In addition, groups of rats were orally dosed with either 35S-labeled N-acetyl-L-methionine or L-methionine. The animals were killed 3, 24, and 168 hours after dosing. Urine and feces were collected, and tissues were excised for 35S determinations. With either route of dosing, N-[1-14C]acetyl-L-methionine yielded the same amount of 14CO2 as sodium [1-14C]acetate over a 24-hour period. The acetate moiety of N-[1-14C]acetyl-D-methionine is not readily metabolized to 14CO2. Within each time period after dosing, the tissue distribution of 35S from 35S-labeled N-acetyl-L-methionine and L-methionine was similar. Protein specific activities for the two isotopes were also the same. After 168 hours, 30% of both isotopes of 35S appeared in the urine and feces, and the two isotopes were similarly distributed in the organic -S and inorganic -S fractions of urine. The studies show that L-methionine from N-acetyl-L-methionine is metabolically equivalent to free L-methionine. This conclusion is consistent with rat feeding studies showing that N-acetyl-L-methionine is nutritionally equivalent to L-methionine.

Acetates↗

Direct detection and evaluation of conversion of D-methionine into L-methionine in rats by stable isotope methodology.

The stereoselective kinetics of methionine enantiomers in rats was investigated to evaluate the fraction that converted from d-methionine to the L-enantiomer using a stable isotope methodology. After bolus i.v. administration of D- or L-[(2)H(3)]methionine, their plasma concentrations and that of endogenous L-methionine were determined by a stereoselective GC-MS method. L-[(2)H(3)]Methionine appeared rapidly after administration of D-[(2)H(3)]methionine, whereas D-[(2)H(3)]methionine was not detected after administration of L-[(2)H(3)]methionine. The fraction of conversion of D-[(2)H(3)]methionine into L-[(2)H(3)]methionine was estimated using the area under the plasma concentration vs. time curve of L-[(2)H(3)]methionine on D-[(2)H(3)]methionine administration and total clearance of L-[(2)H(3)]methionine on L-[(2)H(3)]methionine administration, and that fraction was >90%. This result demonstrates that almost all i.v. administered D-methionine is converted into the L-enantiomer in vivo.

Animals↗

Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet.

The alleviation mechanism of methionine toxicity by dietary glycine was investigated in weanling rats fed a high-methionine diet. When rats were fed a 10% casein diet containing 2% methionine, the activities of methionine adenosyltransferase, cystathionine beta-synthase, and cystathionine gamma-lyase, which participate in the methionine metabolism in the transsulfuration pathway, were significantly enhanced. But the addition of 2% glycine to the high methionine diet did not cause further increase in these enzyme activities; the activities of methionine adenosyltransferase and cystathionine beta-synthase were rather decreased while cystathionine gamma-lyase activity was not altered. Methionine transaminase activity was essentially insensitive to the dietary addition of methionine and glycine. In rats fed a high methionine diet, the hepatic methionine level was significantly increased with a concomitant decrease in the levels of glycine, serine, and threonine. The addition of glycine to the high methionine diet effectively suppressed the enhancement of the hepatic methionine level and almost completely restored the glycine level, but it only partially restored the serine level and further decreased the threonine level. From these results, it is suggested that the alleviating effect of dietary glycine on methionine toxicity is primarily elicited by the restoration of the hepatic glycine level rather than by an increase in hepatic enzyme activity.

Amino Acids↗

Simultaneous determination of methionine sulfoxide and methionine in blood plasma using gas chromatography-mass spectrometry.

Methionine sulfoxide is an oxidation product of methionine with reactive oxygen species via 2-electron-dependent mechanism. Such oxidants can be generated from activated neutrophils; therefore, methionine sulfoxide can be regarded as a biomarker of oxidative stress in vivo. We describe here a method for the simultaneous determination of methionine sulfoxide and methionine in blood plasma using gas chromatography-mass spectrometry with isotopically labeled compounds as internal standards. This method comprises the inclusion of [Me-13C, Me-2H(3)]methionine sulfoxide and [Me-13C, Me-2H(3)]methionine into plasma, the removal of plasma proteins using acetonitrile, the purification of amino acids with cation-exchange chromatography, and the derivatization of methionine sulfoxide and methionine to their corresponding tert-butyldimethylsilyl derivatives using N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide. Quantitation was performed by electron impact mode. The levels of methionine sulfoxide in healthy human blood plasma were 4.0 +/- 1.0 microM (means +/- SD, n = 8), indicating that approximately 10% of methionine is detected as the oxidized form in healthy human plasma. The ratio of methionine sulfoxide in total methionine increased with treatment of human blood with phorbol 12-myristate 13-acetate, while this ratio remained constant in plasma from alloxan-induced hyperglycemic rabbits. These results indicate that this method is applicable for plasma samples and methionine sulfoxide can represent oxidative stress caused by nonradical oxidation in vivo.

Animals↗

Utilization of the D- and L-isomers of methionine and methionine hydroxy analogue as determined by chick bioassay.

Young chicks were fed sulfur-amino acid (SAA) deficient soy protein or crystalline amino acid diets to evaluate the relative efficacy of the D- and L-isomers of methionine and 2-hydroxy-4-(methylthiobutyrate)Ca (OH-methionine). With crystalline amino acid diets, D-OH-methionine ([alpha] D25 = +24.3) was decisively superior to L-OH-methionine ([alpha] D25 = -25.3) as a source of methionine activity. The D-isomer of OH-methionine was also much more toxic than the L-isomer as measured by magnitude of growth depression and severity of hemolytic anemia. DL-OH-methionine was intermediate in toxicity between the pure D- and L-isomers, but its efficacy for growth promotion was greater than what would have been predicted from its (equal) content of the two isomers. With methionine, the L-isomer was superior in growth-promoting efficacy to the D-isomer; DL-methionine, however, more nearly paralleled the response to L- than to D-methionine. In all cases where the crystalline amino acid diet was fed, regardless of isomeric form, methionine was vastly superior to OH-methionine as a source of SAA activity. With the soy-protein diet, on the other hand, differences in efficacy between methionine and OH-methionine were minimal, and isomeric form was of lesser consequence.

Amino Acids, Sulfur↗

Transport and utilization of D-methionine and other methionine sources in Escherichia coli.

The transport and utilization of D-methionine was investigated in several strains of Escherichia coli K-12. Wild-type cells exhibit a single transport system with a Km of 1.16 muM. This activity exhibits a specificity similar to that of the uptake of L-methionine. The activity toward the D-isomer and the high-affinity uptake of L-methionine are lost in strains mutant in metD, along with the ability to utilize D-methionine as methionine source. Both activities respond identically to gene dosage of metD and are both restored in revertants or transductants. However, although L-methionine is a potent inhibitor of D-methionine uptake, D-methionine has little or no effect on the uptake of the L-isomer. No mutants altered in the uptake of only one of the two isomers were found in a screening. Regulation of both activities was similar in their response to the internal methionine pool, and some evidence was suggestive of partial repressive control of these activities. The evidence is most consistent with the role of the metD product as a common step for two methionine-specific uptake systems, but other gene products may represent the initial substrate binding sites. This system also appears to be involved in the uptake of N-acetyl methionine and methionine sulfoxide and methionine sulfoximine. The uptake of the keto analogue of methionine, alpha-keto-gamma-methiol butyrate, appears to be mediated by a separate system specific for alpha-keto straight-chain acids 5- to 6-carbon units in length.

Binding, Competitive↗

Methionine metabolism in apple tissue: implication of s-adenosylmethionine as an intermediate in the conversion of methionine to ethylene.

If S-adenosylmethionine (SAM) is the direct precursor of ethylene as previously proposed, it is expected that 5'-S-methyl-5'-thioadenosine (MTA) would be the fragment nucleoside. When [Me-(14)C] or [(35)S]methionine was fed to climacteric apple (Malus sylvestris Mill) tissue, radioactive 5-S-methyl-5-thioribose (MTR) was identified as the predominant product and MTA as a minor one. When the conversion of methionine into ethylene was inhibited by (l)-2-amino-4-(2'-aminoethoxy)-trans-3-butenoic acid, the conversion of [(35)S] or [Me(14)C]methionine into MTR was similarly inhibited. Furthermore, the formation of MTA and MTR from [(35)S]methionine was observed only in climacteric tissue which produced ethylene and actively converted methionine to ethylene but not in preclimacteric tissue which did not produce ethylene or convert methionine to ethylene. These observations suggest that the conversion of methionine into MTA and MTR is closely related to ethylene biosynthesis and provide indirect evidence that SAM may be an intermediate in the conversion of methionine to ethylene.When [(35)S]MTA was fed to climacteric or preclimacteric apple tissue, radioactivity was efficiently incorporated into MTR and methionine. However, when [(35)S]MTR was administered, radioactivity was efficiently incorporated into methionine but not MTA. This suggests that the sulfur of MTA is incorporated into methionine via MTR. A dual label experiment with [(35)S, Me-(3)H]MTA indicates that the CH(3)S group of MTA was transferred as a unit to form methionine.A scheme is presented for the production of ethylene from methionine, the first step being the activation of methionine by ATP to give SAM. SAM is fragmented to give ethylene, MTA, and other products. MTA is then hydrolyzed to MTR which donates its methylthio group to a four-carbon acceptor to reform methionine.

Journal Article↗

Methionine metabolism in mammals. Adaptation to methionine excess.

We conducted a systematic evaluation of the effects of increasing levels of dietary methionine on the metabolites and enzymes of methionine metabolism in rat liver. Significant decreases in hepatic concentrations of betaine and serine occurred when the dietary methionine was raised from 0.3 to 1.0%. We observed increased concentrations of S-adenosylhomocysteine in livers of rats fed 1.5% methionine and of S-adenosylmethionine and methionine only when the diet contained 3.0% methionine. Methionine supplementation resulted in decreased hepatic levels of methyltetrahydrofolate-homocysteine methyltransferase and increased levels of methionine adenosyltransferase, betaine-homocysteine methyltransferase, and cystathionine synthase. We used these data to simulate the regulatory locus formed by the enzymes which metabolize homocysteine in livers of rats fed 0.3% methionine, 1.5% methionine, and 3.0% methionine. In comparison to the model for the 0.3% methionine diet group, the model for the 3.0% methionine animals demonstrates a 12-fold increase in the synthesis of cystathionine, a 150% increase in flow through the betaine reaction, and a 550% increase in total metabolism of homocysteine. The concentrations of substrates and other metabolites are significant determinants of this apparent adaptation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗