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G Cederblad

Publications and source records attributed to G Cederblad.

At least 19 recordsLinked to original sources
PubMed1992

Effects of fat availability on acetyl-CoA and acetylcarnitine metabolism in rat skeletal muscle.

This study was designed to examine the effects of stimulation and fat availability on the contents of acetyl coenzyme A (acetyl-CoA), free CoA (CoASH), acetylcarnitine, and free carnitine in the oxidative fiber types of rat skeletal muscle. Hindlimb muscles were perfused with no exogenous free fatty acids (FFA) or high FFA (0.93 +/- 0.03 mM) for 10 min at rest and during isometric, tetanic stimulation. Soleus (SOL) and red gastrocnemius (RG) muscles were sampled prior to perfusion and following rest perfusion and 1 and 5 min of stimulation. The SOL muscle contains predominantly slow oxidative (SO) fibers and the RG contains 56% fast oxidative-glycolytic (FOG) and 35% SO fibers. O2 uptake and tetanic tension production were similar in the fat-free and high FFA treatments. Rest perfusion with high FFA increased acetyl-CoA from 14.6 +/- 1.0 to 20.1 +/- 2.5 nmol/g dry muscle (dm) and acetylcarnitine from 0.12 +/- 0.01 to 0.78 +/- 0.18 mumol/g dm in the RG, while fat-free perfusion had no effect. The SOL results were similar as high FFA increased acetyl-CoA from 7.7 +/- 1.0 to 14.2 +/- 3.1 nmol/g dm and acetylcarnitine from 0.14 +/- 0.02 to 0.49 +/- 0.09 mumol/g dm. Stimulation increased acetyl-CoA and acetylcarnitine to values above rest in SOL and RG in both treatments and removed all fat-free and high-fat differences. The decreases in CoASH and free carnitine were reciprocal to the increases in acetyl-CoA and acetylcarnitine at all time points in both muscles such that total CoA and carnitine were constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗
PubMed1992

Caffeine ingestion and muscle metabolism during prolonged exercise in humans.

We examined the effects of a high-caffeine dose on endurance performance and muscle acetyl group metabolism during prolonged exercise. Eight subjects cycled to exhaustion at approximately 80% maximal oxygen uptake (VO2max) 1 h after ingestion of 9 mg/kg body wt dextrose (Pl) or caffeine (Caf). In the Pl trial, muscle biopsies were taken at rest (1 h postingestion) and at 15 min and exhaustion during exercise. The Caf trial followed the same protocol 1 wk later, with an additional biopsy at the time corresponding to Pl exhaustion. The subjects cycled significantly longer during the Caf trial (96.2 +/- 8.8 min) than in the Pl trial (75.8 +/- 4.8 min). Net glycogenolysis during the initial 15 min of cycling was reduced in the Caf vs. Pl trial (4.7 +/- 1.5 vs. 10.6 +/- 1.3 mmol.kg dry muscle-1.min-1; P less than 0.05). Muscle citrate concentration was increased at rest with Caf (0.59 +/- 0.07 vs. 0.37 +/- 0.05 mmol/kg dry muscle; P less than 0.05) but increased to similar values in both trials during cycling. Caf elevated the acetyl-CoA/CoA-SH ratio at rest (0.316 +/- 0.046 vs. 0.201 +/- 0.023; P less than 0.05) but had no effect on the increases in muscle acetyl-CoA and acetylcarnitine during exercise. The results indicate that Caf before exercise decreased muscle glycogenolysis by approximately 55% over the first 15 min of exercise at approximately 80% VO2max. This "spared glycogen" was available late in exercise and coincided with a prolonged time to exhaustion. Increased utilization of intramuscular triacylglycerol and/or extramuscular free fatty acids after caffeine ingestion may inhibit carbohydrate use at rest and early during exercise via elevations in muscle citrate and the acetyl-CoA/CoA-SH ratio. Muscle acetyl-CoA and acetylcarnitine were maintained above resting contents even at exhaustion when muscle glycogen was depleted.

Acetyl Coenzyme A↗
PubMed1992

PDC activity and acetyl group accumulation in skeletal muscle during prolonged exercise.

Seven subjects cycled to exhaustion [58 +/- 7 (SE) min] at approximately 75% of their maximal oxygen uptake (VO2max). Needle biopsy samples were taken from the quadriceps femoris muscle at rest, after 3, 10, and 40 min of exercise, at exhaustion, and after 10 min of recovery. After 3 min of exercise, a nearly complete transformation of the pyruvate dehydrogenase complex (PDC) into active form had occurred and was maintained throughout the exercise period. The total in vitro activated PDC was unchanged during exercise. The muscle concentration of acetyl-CoA increased from a resting value of 8.4 +/- 1.0 to 31.6 +/- 3.3 mumol/kg dry wt at exhaustion and that of acetylcarnitine from 2.9 +/- 0.7 to 15.6 +/- 1.6 mmol/kg dry wt. This was accompanied by corresponding decreases in reduced CoA (CoASH) from 45.3 +/- 3.1 to 25.9 +/- 3.1 mumol/kg dry wt and in free carnitine from 18.8 +/- 0.7 to 5.7 +/- 0.5 mmol/kg dry wt. Acetyl group accumulation, in the form of acetyl-CoA and acetylcarnitine, was maintained throughout exercise to exhaustion while the glycogen content decreased by 90%. This suggests that availability of acetyl groups was not limiting to exercise performance despite the nearly total depletion of the glycogen store. The increased acetyl-CoA-to-CoASH ratio during exercise caused inhibition of neither the PDC transformation nor the calculated catalytic activity of active PDC.

Acetyl Coenzyme A↗
PubMed1991

A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue.

A radioactive assay for the determination of pyruvate dehydrogenase complex activity in muscle tissue has been developed. The assay measures the rate of acetyl-CoA formation from pyruvate in a reaction mixture containing NAD+ and CoASH. The acetyl-CoA is determined as [14C]citrate after condensation with [14C]-oxaloacetate by citrate synthase. The method is specific and sensitive to the picomole range of acetyl-CoA formed. In eleven normal subjects, the active form of pyruvate dehydrogenase (PDCa) in resting human skeletal muscle samples obtained using the needle biopsy technique was 0.44 +/- 0.16 (SD) mumol acetyl-CoA.min-1.g-1 wet wt. Total pyruvate dehydrogenase complex (PDCt) activity was determined after activation by pretreating the muscle homogenate with Ca2+, Mg2+, dichloroacetate, glucose, and hexokinase. The mean value for PDCt was 1.69 +/- 0.32 mumol acetyl-CoA.min-1.g-1 wet wt, n = 11. The precision of the method was determined by analyzing 4-5 samples of the same muscle piece. The coefficient of variation for PDCa was 8% and for PDCt 5%.

Acetyl Coenzyme A↗
PubMed1991

Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise.

The changes in the muscle contents of CoASH and carnitine and their acetylated forms, lactate and the active form of pyruvate dehydrogenase complex were studied during incremental dynamic exercise. Eight subjects exercised for 3-4 minutes on a bicycle ergometer at work loads corresponding to 30, 60 and 90% of their VO2max. Muscle samples were obtained by percutaneous needle biopsy technique at rest, at the end of each work period and after 10 minutes of recovery. During the incremental exercise test there was a continuous increase in muscle lactate, from a basal value of 4.5 mmol kg-1 dry weight to 83 mmol kg-1 at the end of the final period. The active form of pyruvate dehydrogenase complex increased from 0.37 mmol acetyl-CoA formed per minute per kilogram wet weight at rest to 0.80 at 30% VO2max, 1.28 and 1.25 at 60 and 90% VO2max, respectively. Both acetyl-CoA and acetylcarnitine increased at the two highest work loads. The increase of acetyl-CoA was from 12.5 mumol kg-1 dry weight at rest to 27.3 after the highest work load and for acetylcarnitine from 6.0 mmol kg-1 dry weight to 15.2. The CoASH and free carnitine contents fell correspondingly. There was a close relationship between acetyl-CoA and acetylcarnitine accumulation in muscle during exercise, with a binding of approximately 500 mol acetyl groups to carnitine for each mole of acetyl-CoA accumulated. The results imply that the carnitine store in muscle functions as a buffer for excess formation of acetyl groups from pyruvate catalyzed by the pyruvate dehydrogenase complex.

Acetyl Coenzyme A↗
PubMed1990

Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle.

Radioisotopic assays for the determination of acetyl-CoA, CoASH, and acetylcarnitine have been modified for application to the amount of human muscle tissue that can be obtained by needle biopsy. In the last step common to all three methods, acetyl-CoA is condensed with [14C]oxaloacetate by citrate synthase to give [14C]-citrate. For determination of CoASH, CoASH is reacted with acetylphosphate in a reaction catalyzed by phosphotransacetylase to yield acetyl-CoA. In the assay for acetylcarnitine, acetylcarnitine is reacted with CoASH in a reaction catalyzed by carnitine acetyltransferase to form acetyl-CoA. Inclusion of new simple steps in the acetylcarnitine assay and conditions affecting the reliability of all three methods are also described. Acetylcarnitine and free carnitine levels in human rectus abdominis muscle were 3.0 +/- 1.5 (SD) and 13.5 +/- 4.0 mumol/g dry wt, respectively. Values for acetyl-CoA and CoASH were about 500-fold lower, 6.7 +/- 1.8 and 21 +/- 8.9 nmol/g dry wt, respectively. A strong correlation between acetylcarnitine (y) and short-chain acylcarnitine (x), determined as the difference between total and free carnitine, was found in biopsies from the vastus lateralis muscle obtained during intense muscular effort, y = 1.0x + 0.5; r = 0.976.

Acetyl Coenzyme A↗
PubMed1990

Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition.

Total and free carnitine and acylcarnitine concentrations were analyzed in whole blood and plasma in 12 children with a mean age of 68.4 +/- 42.9 months who had received carnitine-free total parenteral nutrition (TPN) for an average of 4 years. The purpose of the study was to see if the children had become carnitine deficient and, if so, whether this correlated with poor lipid clearance. Compared to controls, the TPN-dependent children had significantly decreased concentrations of total and free carnitine in blood (26.6 +/- 9.4 (SD) mumols/L vs. 43.3 +/- 9.1 mumols/L, p less than 0.001, and 17.1 +/- 7.7 mumols/L vs. 35.2 +/- 8.1 mumols/L, p less than 0.001, respectively). Similar results were found in plasma (total carnitine of 19.0 +/- 8.0 mumols/L vs. 41.9 +/- 5.2 mumols/L, p less than 0.001, and free carnitine of 15.7 +/- 7.3 mumols/L vs. 36.1 +/- 5.2 mumols/L, p less than 0.001, respectively). The acylcarnitine concentration in plasma was decreased in the TPN children (3.3 +/- 1.5 mumols/L vs. 5.8 +/- 3.0 mumols/L, p less than 0.01) compared to controls. Despite the low carnitine concentrations, serum triglyceride levels and serum free fatty acid levels were within the normal range. There was no correlation between carnitine concentrations in plasma and serum triglyceride and free fatty acid levels. Our data show that children receiving carnitine-free TPN for many years developed markedly decreased concentrations of carnitine in blood and plasma. However, no adverse effects of the low carnitine levels were found on triglyceride and free fatty acid metabolism under stable conditions.

Carnitine↗
PubMed1990

Parenteral nutrition in preterm neonates with and without carnitine supplementation.

The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found.

Alanine↗
PubMed1990

Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse.

Treadmill exercise of 2-min duration and increasing intensity resulted in increased formation of acetyl-CoA and acetylcarnitine in working muscle of Thoroughbred horses. At high work intensities a plateau was reached for both acetyl-CoA (approximately 50 mumols/kg dry muscle) and acetylcarnitine (approximately 20 mmol/kg dry muscle). Postexercise concentrations were significantly (P less than 0.001) correlated; [acetylcarnitine] = 349.[acetyl-CoA] + 2.4. The results indicate that approximately 350 mumols acetylcarnitine were accumulated for every 1 mumol acetyl-CoA. Under the conditions of exercise used it is probable that most of the acetyl-CoA formed is generated through the intramitochondrial decarboxylation of pyruvate. The acetyl groups of acetyl-CoA are apparently redistributed throughout the whole cell through formation of acetylcarnitine, which readily transverses the mitochondrial membrane. Despite the redistribution, however, the close correlation between acetylcarnitine and acetyl-CoA would indicate that equilibrium was maintained and that neither acetylcarnitine transferase nor carnitine/acetylcarnitine translocase were rate limiting. There is some question as to whether the changes observed relate directly to exercise itself or to the state in muscle 10 s or more after exercise.

Acetyl Coenzyme A↗
PubMed1978

Effect of thyroxine treatment on carnitine levels in mice.

The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.

Animals↗
PubMed1978

Improved continuous-flow (SMAC) determination of serum albumin.

The albumin values determined by the bromcresol green methods do not compare well with values by more specific methods for albumin determination. The discrepancies have been related to, among other things, acute-phase reactants and are especially pronounced in the lower albumin range. These disadvantages are also inherent in a routine continuous-flow method for albumin (SMAC). The bromcresol green method has been improved considerably by shortening the reaction time before the absorbance is measured, as is described here. The modified method yields values that better agree with those by more specific methods and an influence of acute-phase reactants is no longer observed.

Autoanalysis↗
PubMed1977

Physical training in man. Skeletal muscle metabolism in relation to muscle morphology and running ability.

The metabolic and morphologic adaptation to physical training in skeletal muscle tissue of eleven middle-aged, physically untrained men was studied. Muscle biopsies were taken from the vastus lateralis before, after 8 weeks and after 6 months of physical training for analysis of metabolic and morphologic variables. Glucose tolerance test indicated increased insulin sensitivity after 6 months of physical training. The activities of glycogen phosphorylase, hexokinase and glucose-6-P-dehydrogenase were increased but other enzymes involved in glycogen turnover and glycolysis were unchanged after 6 months of physical traning. The activities of citrate synthase and cytochrome-c-oxidase, representing the oxidative capacity were significantly increased already after 8 weeks of physical training. The incorporation rate of palmitate-carbon into CO2 and triglycerides increased, and the incorporation rate of leucine-carbon into CO2 decreased with 6 months of physical training. The fiber diameter of both Type 1- and Type 2-fibers increased, while the mitochondrial volume increased predominantly in Type 2-fibers. Significant correlations were found between metabolic, physiologic and morphologic variables before and after physical training. The results indicate an increased oxidative capacity, mainly located to Type 2-fibers, and an increased utilization of fatty acids in response to this type of physical training.

Carnitine↗
PubMed1977

Carnitine concentration in skeletal muscle tissue from patients with diabetes mellitus.

L-Carnitine concentration was determined in vastus lateralis and abdominal rectus muscle tissue from 15 patients with diabetes mellitus and 66 controls. Nine of the diabetics were treated with diet and hypoglycemic drugs only and six with insulin. The carnitine concentration was determined enzymatically with labeled [I-14C] acetyl-coenzyme-A as a substrate and given per weight of non-collagen protein. The concentration in muscle tissue did not differ significantly between patients and controls. Patients with insulin-treated diabetes had the same concentration of carnitine in muscle tissue as those treated with hypoglycemic drugs. The drastic decreases in carnitine muscle concentration and in carnitine body pool seen in alloxan-diabetic rats are not observed in skeletal muscle of diabetic humans.

Acetyl Coenzyme A↗
PubMed1977

Variations in blood coagulation, fibrinolysis, platelet function and various plasma proteins during the menstrual cycle.

The variations in the number of platelets, platelet retention, blood coagulation, fibrinolysis and various plasma proteins were studied during the menstrual cycle in 30 normal women. Blood samples were taken on 6 occasions; day 1, 2, and 3 of menstruation, day 5-9 (follicular phase), day 12-16 (around ovulation), and day 19-23 (luteal phase), respectively. The concentration of fibrinogen was lower during menstruation than in the luteal phase. Factor II-VII-X and platelet retention were lowest and the recalcification time was shortest during the menstruation. The number of platelets was highest in the ovulatory phase. The fibrinolytic activity was higher in the luteal phase and during the menstruation than in the follicular phase. The results might indicate an intrauterine clotting during the menstruation. The close correlations between the variations of most of the plasma proteins indicate the presence of some general not identified factor which is probably not the variation in the intravascular water content.

Adult↗
PubMed1977

Coagulation factors and other plasma proteins during abstinence after heavy alcohol consumption in chronic alcoholics.

Coagulation factors and other plasma proteins were studied in 19 male chronic alcoholics during the first abstinence week after a period of heavy alcohol consumption. In spite of a decade of chronic alcoholism and a daily alcohol consumption before admission of more than twice the 'normal' alcohol-metabolizing capacity, the data indicated a well-preserved protein-synthesizing capacity. In fact, the mean levels of some liver-synthesized proteins were above the upper reference limits. Minor changes within the reference ranges during the abstinence suggested a declining acute inflammatory reaction after cessation of intoxication.

Adult↗
PubMed1977

Application of a method for correcting an observed regression between change and initial value for the bias caused by random errors in the initial value.

When studying the correlation between the change of a variable during treatment and the value before treatment, random errors (errors of measurement as well as intra-individual biological variation) may yield seriously biased results. In the present work a method to adjust for this bias is presented. The method was applied to data from blood coagulation factor and plasma protein analyses in chronic alcoholics before and after one week of abstinence. It was found that many of the significant correlations were lost when the data were adjusted.

Adult↗