Enzymes and metabolites of cysteine metabolism in nonhepatic tissues of rats show little response to changes in dietary protein or sulfur amino acid levels

In liver, cysteine dioxygenase (CDO), cysteinesulfinate decarboxylase (CSD), and gamma-glutamylcysteine synthetase (GCS) play important regulatory roles in the metabolism of cysteine to sulfate, taurine and glutathione. Because glutathione is released by the liver and degraded by peripheral tissues that express gamma-glutamyl transpeptidase, some peripheral tissues may be exposed to relatively high concentrations of cysteine. Rats were fed diets that contained low, moderate or high concentrations of protein or supplemental cysteine or methionine for 2 wk, and CDO, CSD and GCS activities, concentrations and mRNA levels and the concentrations of cysteine, taurine and glutathione were measured in liver, kidney, lung and brain. All three enzymes in liver responded to the differences in dietary protein or sulfur amino acid levels, but only CSD in kidney and none of the three enzymes in lung and brain responded. Renal CSD activity was twice as much in rats fed the low protein diet as in rats fed the other diets. Changes in renal CSD activity were correlated with changes in CSD concentration. Some significant differences in cysteine concentration in kidney and lung and glutathione and taurine concentrations in kidney were observed, with higher concentrations in rats fed higher levels of protein or sulfur amino acids. In liver, the changes in cysteine level were consistent with cysteine-mediated regulation of hepatic CDO activity, and changes in taurine level were consistent with predicted changes in cysteine catabolism due to the changes in cysteine concentration and CDO activity. Changes in renal and lung cysteine, taurine or glutathione concentrations were not associated with a similar pattern of change in CDO, CSD or GCS activity. Overall, the results confirm the importance of the liver in the maintenance of cysteine homeostasis.     

The effect of protein supplementation on lactate accumulation during submaximal and maximal exercise.

Eleven subjects performed a graded exercise test after 1 week of protein supplementation (PRO) or glucose polymer placebo (CON), randomly assigned in a double blind fashion. The exercise consisted of 3-min graded exercise bouts separated by 10 min of active recovery at zero pedal resistance. Subjects then performed a 30-sec Wingate test (WIN) to assess performance during supramaximal exercise. Blood samples were obtained in the last 15 sec of each exercise and recovery period. PRO resulted in a decrease in blood lactate following 120% VO2max and WIN, an increase in blood alanine at all time points, and lower postexercise muscle lactate and glycogen. Resting muscle GPT activity was 47% higher during the PRO trial. Mean power output during the WIN did not differ between PRO and CON. The WIN fatigue index was not significantly different between PRO and CON. The increased alanine may reflect increased transamination of pyruvate, thereby reducing the accumulation of lactate, which in turn had a marginal effect on performance during supramaximal exercise.     

Phosphatidylserine and caffeine attenuate postexercise mood disturbance and perception of fatigue in humans

Phosphatidylserine (PS) may attenuate the adverse effects of physical fatigue. Therefore, we investigated the effects of a multi-ingredient supplement containing 400 mg/d PS and 100 mg/d caffeine (supplement [SUP]) for 2 weeks on measures of cognitive function (CF), reaction time (RT), and mood (MD) following an acute exercise stress. It is hypothesized that PS will maintain preexercise CF and RT scores, while attenuating postexercise fatigue. Participants completed 2 acute bouts of resistance exercise (T1 and T2) separated by 2-week ingestion of SUP or control (CON). Outcome measures were assessed pre- and postexercise. When collapsed across groups, a significant decrease in RT performance was seen in the 60-second reaction drill from pre- to postexercise at T1. All other RT tests were similar from pre- to postexercise at T1. Reaction time was not significantly changed by PS. When collapsed across groups, a significant increase in performance of the serial subtraction test was seen. A significant increase (8.9% and 7.1%) in the number of correct answers and a significant decrease (8.0% and 7.5%) in time to answer were seen from pre- to postworkout at T1 and T2, respectively. A significant increase in total MD score from pre- to postworkout was observed for CON but not for PS at T2. Phosphatidylserine significantly attenuated pre- to postexercise perception of fatigue compared to CON. Ingestion of SUP for 14 days appears to attenuate postexercise MD scores and perception of fatigue, but does not affect CF or RT, in recreationally trained individuals.     

Effects of cysteine-containing compounds on biosynthesis of triacylglycerol and cholesterol and anti-oxidative protection in liver from mice consuming a high-fat diet

Effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-propyl cysteine (SPC) and cysteine on enzymes participating in biosynthesis of TAG and cholesterol, and antioxidant protection in liver from mice consuming a high-saturated fat diet was examined. The high-fat diet provided 70 % fat energy, in which saturated fat was 55 % of total fat. NAC, SEC, SPC or cysteine, each agent at 1 g/l, was directly added into the drinking water as a supplement for 4 weeks. Results showed high saturated fat significantly increased hepatic TAG and total cholesterol contents (P < 0.05) via enhancing the activity and mRNA expression of malic enzyme, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P < 0.05). The intake of NAC, SEC or SPC significantly decreased TAG and total cholesterol levels (P < 0.05) via lowering the activity and mRNA expression of these three lipogenic-related enzymes (P < 0.05). NAC, SEC or SPC treatment also significantly suppressed high saturated fat-induced hepatic mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 (P < 0.05). High saturated fat decreased hepatic content of glutathione, and the activity of catalase and glutathione peroxidase (P < 0.05). The intake of NAC, SEC or SPC significantly increased hepatic glutathione content (P < 0.05), restored the activity and mRNA expression of glutathione peroxidase, and alleviated the high saturated fat-induced oxidative stress (P < 0.05). These results support that NAC, SEC and SPC are potent agents for affecting hepatic biosynthesis of TAG and cholesterol, and protecting liver against high saturated fat-associated oxidative damage.     

Energy intake and appetite-related hormones following acute aerobic and resistance exercise

Previous research has shown that resistance and aerobic exercise have differing effects on perceived hunger and circulating levels of appetite-related hormones. However, the effect of resistance and aerobic exercise on actual energy intake has never been compared. This study investigated the effect of an acute bout of resistance exercise, compared with aerobic exercise, on subsequent energy intake and appetite-regulating hormones. Ten active men completed 3 trials in a counterbalanced design: 45 min of resistance exercise (RES; free and machine weights), aerobic exercise (AER; running), or a resting control trial (CON). Following exercise or CON, participants had access to a buffet-style array of breakfast foods and drinks to consume ad libitum. Plasma concentrations of a range of appetite-regulating hormones were measured throughout each trial. Despite significantly higher energy expenditure with AER compared with RES (p < 0.05), there was no difference in total energy intake from the postexercise meal between trials (p = 0.779). Pancreatic polypeptide was significantly higher prior to the meal after both RES and AER compared with CON. In contrast, active ghrelin was lower following RES compared with both CON and AER (p ≤ 0.05), while insulin was higher following RES compared with CON (p = 0.013). In summary, the differential response of appetite-regulating hormones to AER and RES does not appear to influence energy intake in the postexercise meal. However, given the greater energy expenditure associated with AER compared with RES, AER modes of exercise may be preferable for achieving short-term negative energy balance.     

Low vitamin a intake affects milk iron level and iron transporters in rat mammary gland and liver

Marginal vitamin A deficiency is common and can result in a secondary iron (Fe) deficiency. A positive correlation between maternal Fe status and milk Fe was observed in lactating women supplemented with both vitamin A and Fe but not with Fe alone, suggesting effects of vitamin A on mammary gland Fe transport. We hypothesized that low vitamin A intake during lactation elicits differential effects on mammary gland and liver Fe transport and storage proteins, thus affecting milk Fe concentration but not maternal Fe status. We fed rats a control (CON, 4 RE/g) or a marginal vitamin A diet (AD, 0.4 RE/g) through midlactation. Effects on plasma, milk, liver and mammary gland Fe and vitamin A concentrations, and divalent metal transporter-1 (DMT1), ferroportin (FPN), ferritin (Ft), and transferrin receptor (TfR) expression were determined. Dams fed AD were not vitamin A or Fe deficient. Milk and liver vitamin A and Fe and mammary gland Fe concentrations were lower in rats fed AD compared with rats fed CON. Liver TfR expression was higher, whereas mammary gland TfR expression was lower in rats fed AD compared with rats fed CON. Liver Ft was unaffected, whereas mammary gland Ft was lower in rats fed AD compared with rats fed CON. Liver and mammary gland DMT1 and FPN protein levels were lower in rats fed AD compared with rats fed CON. Our results indicate that the mammary gland and liver respond differently to marginal vitamin A intake during lactation and that milk Fe is significantly decreased due to effects on mammary gland Fe transporters, putting the nursing offspring at risk for Fe deficiency.     

The effects of postexercise feeding on saliva antimicrobial proteins

The purpose of this study was to determine the effects of a carbohydrate (CHO) and protein (PRO) drink consumed immediately after endurance exercise on saliva antimicrobial proteins known to be important for host defense. Eleven male runners ran for 2 hr at 75% VO2max on 2 occasions and immediately postexercise were provided, in randomized order, either a placebo solution (CON) or a CHO-PRO solution containing 1.2 g CHO/kg body mass (BM) and 0.4 g PRO/kg BM (CHO-PRO). The solutions were flavor and volume equivalent (12 ml/kg BM). Saliva flow rate, lysozyme, α-amylase, and secretory (S) IgA concentrations were determined from unstimulated saliva samples collected preexercise, immediately postexercise, and every 30 min until 180 min postexercise. CHO-PRO ingestion immediately postexercise resulted in a lower saliva flow rate than with CON at 30 and 60 min postexercise. Saliva lysozyme concentration increased immediately postexercise in both trials compared with preexercise (p< .05), and CHO-PRO ingestion immediately postexercise resulted in a higher saliva lysozyme concentration in the first hour of recovery than with CON (125% greater at 30 min, 94% greater at 60 min; p< .01). Saliva SIgA concentration decreased below preexercise concentrations 90-150 min postexercise (p< .001), with no effect of CHO-PRO. Saliva α-amylase activity was unaffected by exercise or CHO-PRO refeeding. CHO-PRO refeeding did not alter the secretion rates of any saliva variables during recovery. In conclusion, immediate refeeding with CHO-PRO evoked a greater saliva lysozyme concentration during the first hour of recovery after prolonged exercise than ingestion of placebo but had minimal impact on saliva α-amylase and SIgA responses.     

Long-term cysteine fortification impacts cysteine/glutathione homeostasis and food intake in ageing rats

Purpose

Healthy ageing is associated with higher levels of glutathione. The study aimed to determine whether long-term dietary fortification with cysteine increases cysteine and glutathione pools, thus alleviating age-associated low-grade inflammation and resulting in global physiological benefits.

Methods

The effect of a 14-week dietary fortification with cysteine was studied in non-inflamed (NI, healthy at baseline) and in spontaneously age-related low-grade inflamed (LGI, prefrail at baseline) 21-month-old rats. Fifty-seven NI rats and 14 LGI rats received cysteine-supplemented diet (4.0 g/kg of free cysteine added to the standard diet containing 2.8 g/kg cysteine). Fifty-six NI rats and 16 LGI rats received a control alanine-supplemented diet.

Results

Cysteine fortification in NI rats increased free cysteine (P < 0.0001) and glutathione (P < 0.03) in the liver and the small intestine. In LGI rats, cysteine fortification increased total non-protein cysteine (P < 0.0007) and free cysteine (P < 0.03) in plasma, and free cysteine (P < 0.02) and glutathione (P < 0.01) in liver. Food intake decreased over time in alanine-fed rats (r ² = 0.73, P = 0.0002), whereas it was constant in cysteine-fed rats (r ² = 0.02, P = 0.68). Cysteine fortification did not affect inflammatory markers, mortality, body weight loss, or tissue masses.

Conclusion

Doubling the dietary intake of cysteine in old rats increased cysteine and glutathione pools in selected tissues. Additionally, it alleviated the age-related decline in food intake. Further validation of these effects in the elderly population suffering from age-related anorexia would suggest a useful therapeutic approach to the problem.     

Gender and exercise influence on tissue antioxidant vitamin status in rats

Although gender differences in antioxidant status based largely on differing estrogen levels have been postulated, it is not known if other gender based differences in tissue antioxidants exist. This experiment examined whether gender based differences in tissue vitamin C and vitamin E concentration exist, and investigated the possibility of gender based differences in indices of tissue oxidative stress following an acute exercise bout. It was determined that female rats had significantly higher levels of vitamin E in liver and heart tissues than males and that males had significantly more vitamin C in the plantaris muscle than females. However, female rats also had less liver glutathione than males. Acute exercise resulted in significant and equal tissue oxidative stress in both genders as indicated by tissue glutathione status. With some exceptions, tissue vitamin C and vitamin E concentrations were generally unaffected by acute exercise in either gender. Hence, while some gender differences in tissue antioxidant status in rats are evident, these differences do not affect tissue indices of oxidative stress following acute exercise.     

Rat liver glutathione: possible role as a reservoir of cysteine.

Rat liver contains a high concentration (7-8mM) of reduced glutathione and its level changes rapidly when starving or feeding rats. We concluded that one of the functions of liver glutathione was to act as a reservoir of cysteine. When starved rats were fed a protein-free diet, the increase in liver glutathione was dependent on the amount of cysteine added to the diet. A cysteine-dependent increase of glutathione was also observed in rats fed a diet containing gelatin with cysteine, but the increase was relatively lowered compared with rats fed a protein-free diet containing the same amount of cysteine. This suppression of the increase in glutathione was observed much more clearly when the gelatin diet was fortified with tryptophan in addition to cysteine. In the presence of tryptophan, L-[35S]-cysteine in the diet appeared to be incorporated primarily into liver and serum proteins, and degradation of liver glutathione must also have been enhanced. Addition of excess cysteine to the diet masked the effects of gelatin and tryptophan, stimulated glutathione synthesis in the liver as well as incorporation of dietary cysteine into protein fractions. Prolonged starvation of rats or injection of dibutyryl-3',5'-cyclic AMP lowered the glutathione level,but the level did not decrease below 2 to 3 mM. These findings suggest that there may be at least two pools of glutathione. A labile fraction, constituting one-third to one-half the total liver glutathione, probably serves as a reservoir of cysteine which can be released by gamma-glutamyl-transferase when necessary.     

Skim milk as a recovery beverage after exercise is superior to a sports drink for reducing next-day postprandial blood glucose and increasing postprandial fat oxidation

We determined the effect of consuming low–glycemic index (LGI) skim milk compared to a high–glycemic index (HGI) sports drink following evening exercise on fat oxidation and blood lipids after a subsequent high-energy breakfast. We hypothesized that postexercise skim milk consumption, compared to sports drink, would increase fat oxidation and lower harmful blood lipid and glucose concentrations after a next-day high-energy breakfast. In this randomized counterbalanced crossover trial, 20 overweight-obese participants (body mass index ≥ 25 kg/m²) underwent 4 conditions: 90-minute exercise (50% Vo_2peak) followed by sports drink (EX-HGI), exercise followed by isoenergetic skim milk (EX-LGI), exercise followed by water (Exercise), and a control condition (Control). The amount of the sports drink or milk consumed postexercise was based on the energy used during exercise plus 10%. Blood lipids, glucose, and fat oxidation were assessed before and for 6 hours after a high-energy breakfast the next morning. Fat oxidation was highest for EX-LGI (6.7 ± 2.7 g/h) and lowest for EX-HGI (6.0 ± 1.8 g/h) (condition main effect; P = .042). Triglyceride concentration and total area under the curve were higher with EX-HGI than Exercise (1.7 ± 1.6 vs 1.3 ± 1.0 mmol/L, P = .037, and 11.7 ± 9.4 vs 8.6 ± 6.0 mmol L⁻¹ h, P = .005, respectively). Glucose concentration was lower with EX-LGI than EX-HGI (4.1 ± 1.1 vs 4.4 ± 1.1 mmol/L, P = .027). Homeostatic model assessment of insulin resistance was higher with EX-HGI than Control (2.32 ± 1.15 vs 1.86 ± 0.97, P = .005). In conclusion, evening postexercise skim milk consumption, compared with a high-GI sports drink, significantly reduced blood glucose and possibly increased fat oxidation after a high-energy breakfast the next morning.     

Effect of sprint interval exercise on postexercise metabolism and blood pressure in adolescents

The current study examined the effect of sprint interval exercise on postexercise oxygen consumption, respiratory-exchange ratio (RER), substrate oxidation, and blood pressure in adolescents. Participants were 10 normal-weight healthy youth (7 female), age 15-18 years. After overnight fasts, each participant undertook 2 trials in a random balanced order: (a) two 30-s bouts of sprint interval exercise on a cycle ergometer and (b) rested in the laboratory for an equivalent period. Time-matched measurements of oxygen consumption, RER, and blood pressure were made 90 min into recovery, and substrate oxidation were calculated over the time period. Total postexercise oxygen uptake was significantly higher in the exercise than control trial over the 90 min (mean [SD]: control 20.0 [6.0] L, exercise 24.8 [9.8] L; p=.030). After exercise, RER was elevated above control but then fell rapidly and was lower than control 30-60 min postexercise, and fat oxidation was significantly higher in the exercise than control trial 45-60 min postexercise. However, total fat oxidation did not differ between trials (control 4.5 [2.5] g, exercise 5.4 [2.7] g; p=.247). Post hoc tests revealed that systolic blood pressure was significantly lower than in control at 90 min postexercise (control 104 [10] mm Hg, exercise 99 [10] mm Hg; p<.05). These data indicate that acute sprint interval exercise leads to short-term increases in oxygen uptake and reduced blood pressure in youth. The authors suggest that health outcomes in response to sprint interval training be examined in children.     

Ontogenic changes in hepatic glutathione and metallothionein in rats and the effect of a low-sulphur-containing diet

Metallothionein contains about 30% cysteine and is a major protein in newborn rat liver. This protein and glutathione constitute two major intracellular cysteine pools in newborn rat liver. When pregnant rats were fed on a soya-bean-protein diet, low in sulphur amino acids, the hepatic glutathione levels of the dams were decreased. However, this did not affect the levels of glutathione or metallothionein in the pups. The activity of the glutathione-degrading enzyme gamma-glutamyltransferase (EC 2.3.2.2) in the livers of pups was maximum at birth and gradually decreased with age when the hepatic glutathione was transported to the kidney. In the pups born from dams fed on soya-bean-protein diet the decline in the hepatic enzyme activity was delayed, suggesting a continued degradation of glutathione in the liver. These results suggest that even with a maternal nutritional deficiency of sulphur amino acids, the transfer of cysteine to the fetus is not impaired. However, the hepatic intra-organ degradation of glutathione is continued in these pups for a prolonged period after birth compared with pups born from control mothers. The increased degradation of glutathione in the liver may be essential to meet the requirement of cysteine in pups born from dams fed on the soya-bean-protein diet.     

摄入不同量蛋白质对运动大鼠肝脏脂质过氧化作用的影响

采用Ｗｉｓｔｅｒ雄性大鼠，分组饲以７％、１７％、２７％蛋白质水平的饲料，观察运动对大鼠脂质过氧化作用的影响。结果表明：运动可改变肝脏脂质过氧化物的含量，运动后肝脏谷胱甘肽过氧化物酶活性增高，还原型谷胱甘肽含量下降，各组中以１７％蛋白质摄入水平大鼠运动耐力最强。据此可知，衰竭运动可增强脂质过氧化作用，运动对７％蛋白质摄入水平大鼠的影响最大，１７％蛋白质摄入水平可有效地抵御脂质过氧化作用，２７％组未显出这种优势。     

Glutathione turnover is increased during the acute phase of sepsis in rats

Glutathione metabolism during infection has been poorly documented. Glutathione concentrations and synthesis rates were studied in infected rats (2 d after infection) and in pair-fed controls. Glutathione synthesis rates were determined in liver, spleen, lung, small and large intestine, skeletal muscle, heart and blood by a 4-h or 6-h (15)N cysteine infusion. The activities of four hepatic enzymes involved in glutathione metabolism were also determined. Glutathione synthesis rates were significantly greater in liver (+465%), spleen (+388%), large intestine (+109%), lung (+100%), muscle (+91%) and heart (+80%) of infected rats compared with pair-fed controls. Glutathione concentrations were also greater in these tissues but were unaffected in small intestine and lower in blood. In keeping with the stimulation of liver glutathione synthesis, the activities of liver gamma-glutamyl-cysteine synthetase and glutathione reductase were significantly greater in liver of infected rats than of pair-fed rats. From the present study, we estimate that glutathione synthesis accounts for at least 40% of the enhanced cysteine utilization during infection. This increased utilization may be the primary cause of an enhanced cysteine requirement in infection.     

Variation of cysteine level by chlorobenzene-induced pertubation of glutathione metabolism in rat liver

Effects of chlorobenzene-induced alteration in glutathione levels on cysteine metabolism in rat liver were investigated. Male Wistar rats were intraperitoneally injected with chlorobenzene (0.2, 0.5, 1.0 or 2.0 mmol/kg body weight). Both hepatic glutathione and cysteine levels were dose-dependently decreased by the chlorobenzene 6 h after the injection. However, at 24 h, the glutathione in the rats with chlorobenzene increased significantly as compared to that in the rats without chlorobenzene. Concomitant to the elevation in glutathione levels, hepatic glutathione synthesis activities were increased by the chlorobenzene by 68-111%. On the other hand, no significant difference between the rats with and without chlorobenzene was observed as regards cysteine levels at 24 h. Hepatic glutamate, glycine, methionine and serine levels were unaltered but hepatic taurine levels were significantly decreased by the chlorobenzene at both 6 and 24 h. Chlorobenzene administration had no effect on hepatic cystathionine synthase and cystathionase activities. These results indicate that a transient loss of hepatic glutathione, caused by the administration of chlorobenzene, resulted in an acceleration of glutathione synthesis and an increase of cysteine demand in the liver.     

Five cysteine-containing compounds delay diabetic deterioration in Balb/cA mice

The effects of n-acetyl cysteine (NAC), s-allyl cysteine (SAC), s-ethyl cysteine, s-methyl cysteine and s-propyl cysteine (SPC) activity on Balb/cA mice against diabetic complications were examined. These complications included hyperglycemia, hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. To induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive days. Five cysteine-containing compounds at 1 g/L were added to the drinking water. After intake of the 5 cysteine-containing agents for 4 wk, body weight loss, plasma concentrations of glucose and insulin, and fibronectin levels were improved (P < 0.05) in diabetic mice. The administration of these agents restored the glutathione level (P < 0.05), reduced the loss of catalase and glutathione peroxidase activities in kidney and liver (P < 0.05), and decreased glucose-induced lipid oxidation, as assessed by malondialdehyde formation (P < 0.05). In all diabetic mice, the intake of these agents reduced triglyceride levels in plasma and liver (P < 0.05); however, only NAC, SAC and SPC treatments reduced cholesterol level in liver (P < 0.05). These cysteine-containing agents elevated the activity of 2 fibrinolytic factors, protein C and antithrombin III (P < 0.05). The overexpression of interleukin-6 and tumor necrosis factor-alpha in diabetic mice was suppressed by the intake of the 5 cysteine-containing agents (P < 0.05). Via their antioxidant activities, the 5 compounds effectively improved glycemic control, delayed oxidation damage, downregulated inflammatory cytokines, and enhanced anticoagulant activity in diabetic mice. These data support the multiple roles of these agents as potential protective agents for delaying diabetic deterioration.     

Effects of ��-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats

α-Lipoic acid and L-carnosine are powerful antioxidants and are often used as a health supplement and as an ergogenic aid. The objective of this study was to investigate the effects of α-lipoic acid and/or L-carnosine supplementation on antioxidant activity in serum, skin, and liver of rats and blood lipid profiles for 6 weeks. Four treatment groups received diets containing regular rat chow diet (control, CON), 0.5% α-lipoic acid (ALA), 0.25% α-lipoic acid + 0.25% L-carnosine (ALA + LC), or 0.5% L-carnosine (LC). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and lipid peroxidation products, malondialdehyde (MDA) concentrations, were analyzed in serum, skin, and liver. Blood lipid profiles were measured, including triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). Skin and liver SOD activities of the ALA and LC groups were higher than those of the CON group (P < 0.05), but serum SOD activity was higher only in the LC group compared to that in the CON group (P < 0.05). Additionally, only liver GSH-Px activity in the LC group was higher than that of the CON and the other groups. Serum and skin MDA levels in the ALA and LC groups were lower than those in the CON group (P < 0.05). Serum TG and TC in the ALA and ALA + LC groups were lower than those in the CON and LC groups (P < 0.05). The HDL-C level in the LC group was higher than that in any other group (P < 0.05). LDL-C level was lower in the ALA + LC and LC groups than that in the CON group (P < 0.05). Thus, α-lipoic acid and L-carnosine supplementation increased antioxidant activity, decreased lipid peroxidation in the serum, liver, and skin of rats and positively modified blood lipid profiles.     

Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women

Cysteine synthesis from homocysteine is catalyzed by two pyridoxal 5'-phosphate (PLP)-dependent enzymes. This suggests that vitamin B-6 status might affect cysteine and glutathione homeostasis, but it is unclear whether this occurs in humans. We assessed the effects of vitamin B-6 status on static and kinetic parameters of cysteine and glutathione metabolism in healthy female (n=5) and male (n=4) volunteers (20-30 y) before and after 4 wk of dietary vitamin B-6 restriction (<0.5 mg vitamin B-6/d). Rates of reactions related to cysteine metabolism were measured from blood sampled during primed, constant infusions of [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(2)]cysteine that were conducted after an overnight fast at baseline and after the dietary protocol. Vitamin B-6 restriction reduced the concentration of PLP (55.1+/- 8.3 vs. 22.6+/-1.3 nmol/L; P=0.004) and increased concentrations of cystathionine (124%; P<0.001) and total glutathione (38%; P<0.008) in plasma. Concentrations of plasma homocysteine, cysteine, cysteinylglycine, and C-reactive protein (an indicator of systemic inflammation) were not affected by dietary vitamin B-6 restriction. The rate of cysteine synthesis via transsulfuration was below detection limits in this protocol. Neither the fractional synthesis rate of cystathionine nor whole-body cysteine flux was affected by vitamin B-6 restriction. These data indicate that glutathione homeostasis is altered by dietary vitamin B-6 deficiency and appears to be unrelated to cysteine flux under conditions of minimal amino acid intake as evaluated in this study.     

Propargylglycine infusion effects on tissue glutathione levels, plasma amino acid concentrations and tissue morphology in parenterally-fed growing rats

Amino acid solutions currently used for total parenteral nutrition (TPN) contain little cysteine or cystine. Some premature human infants have low liver activities of gamma-cystathionase and presumably require preformed cysteine or cystine. Growing animals tend to have higher liver gamma-cystathionase activity, which makes them unsuitable as models to study effects of CSH precursors. Because propargylglycine (PPG) inhibits gamma-cystathionase specifically, rats infused with PPG as part of a TPN regimen were evaluated as a potential model. Two groups of rats (120-160 g) were infused for 15 d with TPN regimens, one without and one with PPG (40 mumols/d). A third group received the TPN-control regimen, with methionine added at toxic levels. Propargylglycine treatment significantly decreased plasma cystine and taurine concentrations and significantly increased plasma cystathionine concentration without affecting methionine concentration. Propargylglycine treatment significantly decreased brain, muscle, liver, intestine and stomach glutathione concentration without affecting erythrocyte or heart glutathione concentrations. Electron microscopic examination showed no abnormalities in heart and kidney of PPG-treated rats. Hepatocyte glycogen was lower in TPN-fed controls than in orally fed rats and was further reduced in TPN-PPG-fed animals. Growing rats infused with low doses of PPG show promise as an animal model to study a number of important issues concerning human sulfur amino acid metabolism.