Dietary Sulfur-containing Amino Acids Research Articles

The role of mitochondrial bioenergy and system glutathione in deficiency of Coenzyme Q and Complex I

Cytokine Coenzyme Q10 (CoQ10) is an insoluble coenzyme that is a component of the electron transport chain and is involved in oxidative phosphorylation in mitochondria. By a decrease in CoQ10, the energy requirements of the cell are not fully covered: cell division slows down, and the processes of tissue renewal and regeneration are disrupted. In our work, we used a model of mice CoQ9 Knockin (R239X). In homozygous mutant mice, a strong decrease in CoQ7 protein and the accumulation of dimethoxyubiquinone are observed. An impairment of hydrogen sulfide metabolism was previously identified as a significant pathomechanism of primary Coenzyme Q deficiency. The experimental results showed that the disruption of sulfide and glutathione metabolism in Coq9R239X mice is directly dependent on CoQ levels. Therefore, changes in dietary sulfur-containing amino acids do not alter sulfide metabolism and the glutathione system in Coq9R239X mice. As our experiments have shown, an increase in total glutathione is observed only in symptomatic brain tissue. It can be assumed that this is due to oxidative stress in the symptomatic brain tissue, which is often found with mitochondrial dysfunction.

Supplemental Dietary Cystine Elevates Kidney Metallothionein in Rats by a Mechanism Involving Altered Zinc Metabolism

Dietary sulfur-containing amino acids influence zinc and copper status. This study was conducted to investigate the relationship between the status of these elements and tissue metailothionein in rats fed diets supplemented with sulfur-containing amino acids. In a series of experiments, a diet containing 100 g casein/kg diet was unsupplemented or supplemented with L-cystine (3–50 g/kg diet) or L-methionine (3 or 30 g/kg diet). Kidney concentrations of zinc and copper in rats fed the diet supplemented with high levels of cystine (25 or 50 g/kg) were significantly higher than those in rats fed the unsupplemented diet. Kidney concentrations of metallothionein and metallothionein mRNA were also significantly higher in rats fed cystine-supplemented diets. There was a correlation (r = 0.838, P < 0.01) between the levels of zinc and metallothionein in kidney of rats fed the diets with different levels of cystine and zinc. However, in the rats fed the diets with different levels of cystine and copper, the correlation was not as strong (r = 0.587, P < 0.01). The changes in kidney metallothionein concentration due to the addition of 3 or 30 g/kg cystine were associated with parallel changes in serum zinc concentration and in apparent absorption of zinc, but not in serum copper concentration or apparent absorption of copper. Addition of 3 or 30 g methionine/kg diet to the diet did not affect kidney concentrations of metallothionein or zinc. These results indicate that supplementation of cystine to the diet can induce kidney metallothionein through a mechanism involving altered zinc metabolism.

Additional supplementation of sulfur-containing amino acids in the diets improves the intestinal health of turbot fed high-lipid diets

An eight-week feeding trial was conducted to investigate the effects of diets supplemented with three sulfur-containing amino acids (SAA), namely, methionine, cysteine, and taurine, on the intestinal health status of juvenile turbot (Scophthalmus maximus) fed high-lipid diets. Four diets were formulated, namely, a high-lipid control diet (16% lipid, HL) and three SAA-supplemented diets, which were formulated by supplementing 1.5% methionine (HLM), 1.5% cysteine (HLC), and 1.5% taurine (HLT) into the HL control diet, respectively. Each diet was assigned to triplicate tanks, and each tank was stocked with 30 juvenile fish (appr. initial weight, 8 g). The histological and morphometric results showed that dietary SAA supplementation obviously improved the intestinal morphology and integrity, in particular as reflected by higher height of microvilli and mucosal folds. Dietary SAA supplementation, in particular cysteine, up-regulated the gene expression of mucin-2 and tight junction proteins (ZO-1, Tricellilun and JAM). Dietary SAA supplementation remarkably down-regulated the gene expression of apoptosis-related factors such as p38, JNK, and Bax, expression of pro-inflammatory factors (e.g., NF-κB, AP-1 IL-1β, IL-8, and TNF-α). SAA supplementation resulted in higher antioxidative abilities in the intestine. Additionally, dietary SAA supplementation largely altered the communities of intestinal microbiota. Compared with the HL group, higher relative abundance of potential beneficial bacteria, and lower relative abundance of opportunistic pathogens were observed in SAA-supplemented groups. Dietary taurine supplementation significantly increased the relative abundance of Ligilactobacillus (in particular Lactobacillus murinus) and Limosilactobacillus (especially Lactobacillus reuteri). In conclusion, dietary sulfur-containing amino acids supplementation have promising potential in ameliorating the intestinal inflammation of turbot fed high-lipid diets. Especially dietary cysteine and taurine supplementation have more positive effects on the communities of the intestinal microbiota of turbot.

Cumulative Consumption of Sulfur Amino Acids Intake and Incidence of Diabetes

ObjectivesIncreasing evidence in animal models and humans suggests that diets high in sulfur-containing amino acids (SAA) could be associated a greater risk for type 2 diabetes (T2D). However, data from longitudinal human studies linking dietary SAA intake with T2D is lacking. The present study aimed to examine the association between long-term dietary intake of SAA including total SAAs, methionine, and cysteine and incident T2D in participants of the Framingham Heart Study (FHS). MethodsAdult participants were selected from two prospective FHS cohorts: The Offspring Cohort (followed from 1991 to 2015, n = 3799) and the Third Generation Cohort (followed from 2002 to 2011, n = 4096). Individuals identified as diabetes patients before baseline, having missing diet or covariates data, or reported extreme daily energy intake were excluded. Energy-adjusted intake of dietary SAAs was calculated from responses to a 131-item food frequency questionnaire. Cox proportional hazards models were used to evaluate associations between intakes of SAAs (in quintiles) and risk of T2D in each cohort. A combined analysis was also performed pooling subjects from both cohorts. ResultsOverall, we documented 471 T2D events during 9–23 years of follow-up. In both cohorts, higher SAA intake was associated with a higher risk of T2D after adjustment for demographics, traditional risk factors and related nutrients. Comparing participants in the highest quintile with those in the lowest quintile of intake, adjusted hazard ratios (95% CI) were 1.98 (1.15–3.41) for total intake (P for trend = 0.04) in the Offspring cohort, and 4.37 (1.40–13.67) (P for trend = 0.01) in the Third Generation cohort. In the combination analysis of two cohorts, adjusted hazard ratios (95% CI) were 1.98 (1.23–3.21) for total intake, 2.21 (1.38–3.53) for methionine, and 1.79 (1.12–2.87) for cysteine (P for trends < 0.03). ConclusionsHigher long-term SAA intake was associated with higher risk for T2D in humans, suggesting that dietary patterns emphasizing low SAA intake are protective against development of T2D. Funding SourcesNo funding.

Urinary sulfate excretion and risk of late graft failure in renal transplant recipients - a prospective cohort study.

Hydrogen sulfide (H2S), produced from metabolism of dietary sulfur‐containing amino acids, is allegedly a renoprotective compound. Twenty‐four‐hour urinary sulfate excretion (USE) may reflect H2S bioavailability. We aimed to investigate the association of USE with graft failure in a large prospective cohort of renal transplant recipients (RTR). We included 704 stable RTR, recruited at least 1 year after transplantation. We applied log‐rank testing and Cox regression analyses to study association of USE, measured from baseline 24 h urine samples, with graft failure. Median age was 55 [45–63] years (57% male, eGFR was 45 ± 19 ml/min/1.73 m2). Median USE was 17.1 [13.1–21.1] mmol/24 h. Over median follow‐up of 5.3 [4.5–6.0] years, 84 RTR experienced graft failure. RTR in the lowest sex‐specific tertile of USE experienced a higher rate of graft failure during follow‐up than RTR in the middle and highest sex‐specific tertiles (18%, 13%, and 5%, respectively, log‐rank P < 0.001). In Cox regression analyses, USE was inversely associated with graft failure [HR per 10 mmol/24 h: 0.37 (0.24–0.55), P < 0.001]. The association remained independent of adjustment for potential confounders, including age, sex, eGFR, proteinuria, time between transplantation and baseline, BMI, smoking, and high sensitivity C‐reactive protein [HR per 10 mmol/24 h: 0.51 (0.31–0.82), P = 0.01]. In conclusion, this study demonstrates a significant inverse association of USE with graft failure in RTR, suggesting high H2S bioavailability as a novel, potentially modifiable factor for prevention of graft failure in RTR.

Dietary Sulfur-Containing Amino Acids Are Associated with Higher Prevalence of Overweight/Obesity in Northern Chinese Adults, an Internet-Based Cross-Sectional Study

Background/aims: Elevation of plasma sulfur-containing amino acids (SAAs) is generally associated with higher body mass index (BMI) and unfavorable lipid profiles. It is not known how dietary SAAs relate to these associations in humans. Methods: A convenient tool named internet-based dietary questionnaire for Chinese (IDQC) was used to estimate dietary SAAs intake. A total of 936 participants were randomly recruited and asked to complete the IDQC. Furthermore, 90 subjects were randomly selected to perform a subgroup study. The associations between dietary SAAs and prevalence of obesity, lipid profiles, and status of insulin resistance (IR), inflammation and oxidative stress were assessed. Results: Dietary total SAAs and cysteine of overweight/obese participants were significantly higher. Dietary total SAAs and cysteine were positively associated with BMI and waist circumference. Higher dietary total SAAs were associated with higher prevalence of overweight/obesity. Higher dietary total SAAs and cysteine also associated with higher serum triglyceride (total cholesterol), low density lipoprotein, fasting blood glucose, 2 h-postprandial glucose, and homeostasis model assessment of IR. In the subgroup study, positive associations between dietary SAAs and inflammation biomarkers were also observed. Conclusions: Dietary SAAs are associated with higher prevalence of overweight/obesity, unfavorable lipid profiles and status of IR, and inflammation.

Etiology of Konzo, epidemic spastic paraparesis associated with cyanogenic glycosides in cassava: Role of thiamine deficiency?

Konzo is a syndrome of symmetrical, non-progressive, non-remitting spastic paraparesis occurring in epidemic and endemic forms in several countries in Africa, invariably associated with monotonous consumption of inadequately processed bitter cassava roots (Manihot esculenta) with very minimal protein supplementation.Despite numerous epidemiological, clinical and biochemical studies by authors in several countries aimed at elucidating the etiological mechanisms of Konzo, the etiology remains unknown. High cyanide consumption with low dietary sulfur intake due to almost exclusive consumption of insufficiently processed bitter cassava roots was proposed as the cause of Konzo, but there has been no evidence of a causal association between cyanide consumption and Konzo.In this paper a new etiological mechanism of thiamine deficiency is presented, based on detailed review of the epidemiological, clinical and biochemical features of Konzo. It is postulated that in Konzo patients, a severe exacerbation of thiamine deficiency results from the inactivation of thiamine that occurs when, in the absence of dietary sulfur-containing amino acids; the sulfur in thiamine is utilized for the detoxification of cyanide consumed in improperly processed bitter cassava. Thiamine is known to be rendered inactive when the sulfur in its thiazole moiety is combined with hydrogen cyanide.This hypothesis may stimulate studies examining the role of thiamine in the etiology of Konzo, and may lead to the formulation of strategies for the prevention and treatment of this debilitating disease.

Higher Bioaccessibility of Iron and Zinc from Food Grains in the Presence of Garlic and Onion

Bioavailability of micronutrients iron and zinc is particularly low from plant foods. Hence there is a need to evolve a food-based strategy to improve the same to combat widespread deficiencies of these minerals in a population dependent on plant foods. Dietary sulfur-containing amino acids have been reported to improve the mineral status of experimental animals. Our objective was to examine whether sulfur compound-rich Allium spices have a similar potential of beneficially modulating the mineral bioavailability. In this context, we examined the influence of exogenously added garlic and onion on the bioaccessibility of iron and zinc from food grains. Two representative cereals and pulses each were studied in both raw and cooked condition employing two levels of garlic (0.25 and 0.5 g/10 g of grain) and onion (1.5 and 3 g/10 g of grain). The enhancing effect of these two spices on iron bioaccessibility was generally evidenced in the case of both the cereals (9.4-65.9% increase) and pulses (9.9-73.3% increase) in both raw and cooked conditions. The two spices similarly enhanced the bioaccessibility of zinc from the food grains, the extent of increase in cereals ranging from 10.4% to 159.4% and in pulses from 9.8% to 49.8%. Thus, both garlic and onion were evidenced here to have a promoting influence on the bioaccessibility of iron and zinc from food grains. This novel information has the potential application in evolving a food-based strategy to improve the bioavailability of trace minerals and hence contributes to the human health benefit.

Highlights From The Literature

Highlights From The Literature

Influence of dietary sulfur-containing amino acids on the bioavailability to rats of zinc in corn kernels

A whole-body radioassay method was used to assess effects of supplemental dietary amino acids on absorption by rats of zinc in two varieties of corn kernels labeled either intrinsically or extrinsically with 65Zn. Corn genotypes were a normal type (Nor-corn) with one row of cells in the aleurone layer of the kernel and a variety (Mal-corn) that had multiple rows of cells in the aleurone. In experiment 1, rats fed a basal diet containing 15% soy protein absorbed 64% of the 65Zn provided extrinsically in test meals. When provided test meals that contained intrinsically labeled Nor-corn or Mal-corn kernels, the rats absorbed 64 and 57% of the intrinsic 65Zn, respectively. In rats fed diets that contained supplemental lysine, methionine, or both lysine and methionine, absorption of extrinsic 65Zn averaged 69, 82 and 86% of the dose, respectively. In experiment 2, rats fed the basal diet absorbed 57 and 53% of the intrinsic 65Zn in Nor-corn and Mal-corn kernels, respectively, but rats fed supplemental methionine or cysteine absorbed 73% of the intrinsic 65Zn in either the Nor-corn or Mal-corn kernels. Supplemental methionine or cysteine fed to rats that were marginally zinc deficient enhanced the absorption of 65Zn provided in test meals in the form of either intrinsically labeled corn kernels or as 65Zn-labeled zinc sulfate.

Elevation of the Hepatic Level of Albumin mRNA in Rats Fed a Non-protein Diet Supplemented with Sulfur-containing Amino Acids and Threonine

A nitrogen-sparing action of sulfur-containing amino acids and threonine in rats fed a non-protein diet has been reported from our laboratory. The nutritional significance of dietary sulfur-containing amino acids and threonine on the expression of the albumin gene was investigated. An elevated level of serum albumin and its mRNA in liver was observed in rats fed a non-protein diet supplemented with sulfurcontaining amino acids and threonine, but the level of albumin mRNA of the group supplemented with cystine and threonine was much higher than that of the methionine and threonine supplemented group. Nuclear run-on assay showed an enhanced rate of albumin gene transcription in liver nuclei of rats fed the cystine and threonine supplemented diet. We showed the evidence that cystine is a more efficient amino acid than methionine to maintain the expression of the albumin gene at a high level in rats fed a nonprotein diet.

Effects of a high protein diet on bone formation and calcium metabolism in rats.

The effects of a high protein diet on bone formation and calcium (Ca) metabolism were evaluated in rats using an ectopic endochondral bone induction model. A control diet (18% casein) or a high protein diet (18% casein + 20% lactalbumin) was given to 50-day-old rats. Ten days after the feeding of the experimental diet, rats were intramuscularly implanted with demineralized bone powder (day 0). On day 14 and day 21, the implanted bone powder was harvested, and blood and urine samples were also obtained. Urinary Ca excretion was not increased on day 12-14; however, it was elevated on day 19-21 in rats fed the high protein diet compared with rats fed the control diet. The high protein diet remarkably stimulated urinary sulfate excretion in both sampling periods, which reflected dietary sulfur-containing amino acids contents. Also, rats fed the high protein diet exhibited a decrease in serum Ca concentrations. There was little difference in Ca contents and the activities of alkaline phosphatase and acid phosphatase in the implants between control group and high protein diet group on day 14 and day 21. Histological examination in the implanted demineralized bone powder on day 14 indicated only cartilage in rats fed the high protein diet in contrast to the occurrences of osteogenesis and remodeling in those fed the control diet. Retarded bone formation in rats fed the high protein diet might be owing to, in part at least, a restricted amount of Ca utilized at the stage of cartilage calcification.

Effects of Dietary Methionine, Cystine and Potassium Sulfate on Serum Cholesterol and Urinary Ascorbic Acid in Rats Fed PCB

Liver weight, liver and urinary ascorbic acid levels and serum cholesterol concentration were higher in rats fed polychlorinated biphenyls (PCB) than in controls. The influences of methionine, cystine and potassium sulfate on these metabolic responses were studied. Methionine or equivalent moles of cystine or potassium sulfate were added to a basal diet containing 10% soy protein isolate. The basal diet contained 0.3% of total sulfur-containing amino acids (S-AAs). When methionine was added to the basal diet, maximum gain in body weight was obtained with 0.5% of dietary S-AAs, while the highest values in serum cholesterol and urinary ascorbic acid were obtained with 0.8% of dietary S-AAs in rats fed PCB. Dietary addition of cystine had little effect on body weight gain. Nevertheless, in rat fed PCB, urinary ascorbic acid and serum cholesterol were significantly higher in rats fed the cystine-supplemented diet than in those fed the unsupplementd diet. Addition of potassium sulfate had no effect on body weight gain, urinary ascorbic acid or serum cholesterol. These results suggest that more S-AAs are required for the highest metabolic response to PCB than for maximum growth, and the higher requirement for S-AAs cannot be replaced by inorganic sulfate.

Effect of dietary protein quality on chlorobenzene metabolism and its toxicity in rats

The effect of dietary protein quality on chlorobenzene metabolism and its toxicity was studied. Male weanling Wistar rats were fed diets composed of purified whole egg protein (PEP), wheat gluten, or soybean protein isolate (SPI) at an 18% protein level. After being fed for 3 weeks, the rats were injected with chlorobenzene (1.0mmol/kg body weight) intraperitoneally. In the rats fed the SPI diet, chlorobenzene administration caused hepatic microscopic changes and the elevation of serum GOT and GPT activities. On the other hand, the rats fed the PEP or the gluten diet did not show these toxic symptoms. The hepatic glutathione levels and urinary 4-chlorophenylmercapturic acid excretion of the rats fed SPI diet were markedly lower than those of the other rats. It is considered that the hepatic glutathione level was not sufficient for the conversion of chlorobenzene administered to the mercapturic acid in the rats fed the SPI diet. These results indicate that chlorobenzene metabolism and its toxicity are modified by dietary protein quality, especially the level of dietary sulfur-containing amino acids.

Sulfur Amino Acid Nutrition during Molt in the White-Crowned Sparrow. 2. Nitrogen and Sulfur Balance in Birds Fed Graded Levels of the Sulfur-Containing Amino Acids

-In an effort to estimate a critical concentration of dietary sulfurcontaining amino acids (SAA) for molting birds, we measured nitrogen (N) and sulfur (S) balances before, during, and after postnuptial molt in five groups of White-crowned Sparrows (Zonotrichia leucophrys gambelii) fed isocaloric and isonitrogenous (17.4 kJ/g and 13.5% protein) diets in which SAA concentration ranged from 0.33 to 0.78%. These SAA concentrations approximate those found in natural diets and, as well, bracket the SAA requirements of poultry. Birds from all dietary groups showed positive N and S balances through six temporally equal stages of molt and in the nonmolting periods. Nitrogen retention differed significantly among molt stages but not among dietary groups. The grand average net N retention during molt (total N retention minus basal N retention) was 623 mg/ 25-g bird. Sulfur retention differed significantly among stages and among dietary groups. However, because group differences occurred both during molt and in nonmolt, the net S retention during molt (total S retention minus basal S retention) did not differ significantly among dietary groups. The grand average net S retention during molt was 85.4 mg/25-g bird. These results indicate that molting Whitecrowned Sparrows are typically able to meet the protein and SAA demands of molt through their food (the critical dietary SAA concentrations being less than those likely to be found in natural diets), thus precluding the need to deplete tissue proteins. Avian molt is a type of growth characterized primarily by protein accretion in the form of feathers, and secondarily by the regeneration of other epidermal structures (Spearman 1966, Payne 1972, Chilgren 1975). Despite its morphological restriction, this integumental growth can entail a deposition of a protein mass approaching, or even exceeding, one-fourth of the protein content of a bird's body (Mitchell et al. 1931, Newton 1968, Myrcha and Pinowski 1970, Gavrilov and Dolnik 1974, Chilgren 1977, Carey et al. 1978). Moreover, the cyst(e)ine content of the plumage is disproportionately large compared to its content in the mixed proteins of other tissues or foods (Nitsan et al. 1981, Murphy and King 1982a; cf. F.A.O. 1970, Scott et al. 1982). These observations have, for decades, led avian biologists to question the ability of birds to fulfill the protein demands, or more specifically the sulfur amino acid (SAA) demands, of molt through daily food intake alone. The availability of dietary SAA has often been invoked as a potential explanation for observed changes in body composition, feeding habits, or even energetics during molt (e.g., Hanson 1962, Newton 1968, Gavrilov and Dolnik 1974, Brake et al. 1979), on the assumptions that (1) endogenous SAA reserves will be used if exogenous sources are inadequate, (2) birds may choose foods on the basis of SAA content, or (3) food intake may be increased above caloric needs to fulfill SAA requirements. The results of the few empirical investigations that have been conducted on these subjects thus far are equivocal. Ackerson and Blish (1926) reported a disproportionate nitrogensparing effect of supplemental cystine in molting domestic fowl (Gallus gallus var. domesticus) that were fed otherwise N-free diets. Subsequent experiments (Ackerson et al. 1928) using a corn/casein diet and cystine supplements, however, failed to show a beneficial effect of these supplements on body weight, egg production, or the dynamics of molt in fowl. Similar investigations involving a laying ration and methionine supplementation also were ineffective in shortening the molting period or in increasing post-molt egg production in fowl (Taylor and Russell 1943). Likewise,

Tissue Nonprotein Sulfhydryl Content and Weight Gain of Rats as Affected by Dietary Methionine Level

The effect of dietary methionine level on tissue nonprotein sulfhydryl content (NPSH) and weight gain was systematically evaluated in young adult rats (∼360 g) fed amino acid diets. In 28-day feeding experiments, weight gain and liver and skeletal muscle NPSH increased, but blood NPSH decreased as dietary methionine rose from 0 to 0.8%. The requirement for weight maintenance (0.2% methionine) did not sustain maximum liver and skeletal muscle NPSH, whereas the requirement for maximum weight gain (0.6% methionine) did. Maximum skeletal muscle NPSH was attained by 0.4% methionine and maximum liver NPSH by 0.5% methionine. In another experiment, diets containing 0.4, 0.5, and 0.6% methionine were fed for 1, 8, 29, and 50 days. Liver and skeletal muscle NPSH were lower, whereas blood NPSH was higher with the 0.4% methionine diet. These differences in NPSH were significant at all times for liver, at 8 days for skeletal muscle, and at 29 days for blood. Weight gain did not differ significantly among the groups at any time. In all experiments, weight gain was similar with 0.4 and 0.5% methionine even though liver NPSH was 40–50% higher with 0.5% methionine. The data suggest that tissue NPSH may serve as a cysteine reservoir and spare dietary sulfur-containing amino acids during marginal intake. Also, weight gain may be an unreliable measure of sulfur-containing amino acid needs under some circumstances.

Evidence for an Impairment in the Conversion of Methionine to Cysteine in the Selenium-Deficient Chick

AbstractExperiments were conducted to determine the effects of dietary sulfur-containing amino acids on the etiology of nutritional pancreatic atrophy (NPA) in the Se-deficient chick. Supplementation of a crystalline amino acid diet containing 0.82% methionine with 0.4% L-cystine resulted in significant improvements in growth, efficiency of feed utilization and chick survival, whereas supplementation with 0.4% L-methionine had no effect. L-Cystine supplementation did not significantly affect plasma Se-dependent glutathione peroxidase activity, or prevent NPA. The addition of graded levels of L-cystine to a diet marginally adequate in methionine resulted in maximal gain in body weight and efficiency of feed utilization with 45 mmole half-cystine equivalents per kilogram. Supplementation of the same diet with equimolar amounts of L-methionine did not show significant improvements in these parameters unless the diet was also supplemented with Se. Plasma-free amino acid analyses showed significant reductions ...