Carnitine Pool Research Articles

Carnitine metabolism during exercise

Carnitine is an important cofactor for normal cellular metabolism. Optimal utilization of fuel substrates for ATP generation by skeletal muscle during exercise is dependent on adequate carnitine stores. During short periods of exercise the skeletal muscle carnitine pool is largely segregated from extracellular carnitine. In normal human subjects, only minimal changes in the muscle carnitine pool are observed during exercise at work loads below the lactate threshold. In contrast, at work-loads above the lactate threshold the muscle total carnitine is redistributed from carnitine to acetylcarnitine, with the acetylcarnitine content correlated with the muscle acetyl-CoA and lactate contents. In contrast, in patients with peripheral arterial disease, an accumulation of acylcarnitines is observed at all work loads. Patients with chronic renal failure who are on hemodialysis demonstrate a poor exercise capability which is correlated with a decrease in muscle carnitine content. Carnitine supplementation has been shown to improve exercise tolerance in both peripheral arterial disease and hemodialysis patients. Further work is needed to define the mechanism by which exogenous carnitine improves exercise performance in order to better define potential patient populations for theraphy and to facilitate optimal dosing regimens.

Effect of development and nutritional state on the uptake, metabolism and release of free and acetyl- l-carnitine by the rodent small intestine

Intestinal carnitine levels and the incorporation and release of exogenous, [ 14C]carnitine were compared in intestine from adult rat and guinea pig. Total carnitine levels were 4-fold higher in rat as compared to guinea pig intestine. Retention of label was also 4-fold greater, 4 h after placing carnitine (7 nmol) in the lumen. Carnitine was detected in rat chow (64 nmol/g) but not in guinea pig chow. Intestinal carnitine was reduced 2-fold in rats fed a carnitine-free diet for 2 weeks, suggesting the importance of dietary carnitine in determining intestinal carnitine levels. Two conditions where fatty acid oxidation is increased (fasting and suckling) resulted in elevated carnitine levels and retention. In the 3-day fasted guinea pig, intestinal carnitine increased by 40% and retention of a lumenal dose of [ 14C]carnitine increased about 7-fold after 4 h. During suckling, carnitine levels peaked after 3 days (792 nmol/g) and decreased to near adult levels after 7 days (108 nmol/g). Retention of a lumenal dose of carnitine was greater after 4 h in 1-day old neonatal, than in adult intestine (82% vs. 7% of a 7 nmol dose, respectively). This reflects, in part, the larger intestinal carnitine pool on day 1 (352 nmol/g) than on day 29 (91 nmol/g). The calculated efflux of total intestinal carnitine after 4 h was similar for adults and neonates (72 vs. 58 nmol/g) suggesting that efflux relative to pool size was greater in the adult than in the neonate. Uptake of [ 14C]acetylcarnitine was similar to [ 14C]carnitine in 1-day old animals, but was retained to a lesser extent (36% vs. 82%, respectively) after 4 h. The calculated efflux of total intestinal carnitine when acetylcarnitine was the substrate was about 4-fold that when carnitine was the substrate. Incorporation of [ 14C]carnitine into enterocytes isolated from 3-day old animals was 4-fold greater than into enterocytes isolated from adults (152 vs. 36 pmol/mg protein after 60 min). Active transport of carnitine into enterocytes from neonates, but not from adults is suggested, since labeled free intracellular carnitine reached 4-fold the calculated equilibrium value in neonatal enterocytes, but did not exceed the equilibrium value in adult enterocytes.

Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy

Abnormal carnitine distribution in muscle was found in 22 of 77 patients (29%), with mitochondrial myopathy. Furthermore, total (TC) and free (FC) carnitine levels in muscle were lower in patients than in controls (P < 0.01). Muscle long-chain acylcarnitines (LCAC) were significantly increased in these patients (P < 0.01). Muscle carnitine deficiency was found in 31.5% of patients with lipid storage myopathy (LSM) and in 25.6% of patients with ragged-red fibers (RRF). Therefore, carnitine deficiency can be found in patients with mitochondrial myopathy even in the absence of LSM. Muscle levels of TC and FC were lower in patients with respiratory chain defects than in those with normal respiratory chain (P < 0.01). In contrast, LCAC levels were significantly increased (P < 0.05). Carnitine levels did not differ significantly, among patients with different respiratory-chain defects. Consequently, these patients, owing to their biochemical block, reduce progressively the muscle carnitine pool and subsequent LCAC rise, due to long-chain fatty acid (LCFA) accumulation.

Carnitine measurements in liver, muscle tissue, and blood in normal subjects

We determined carnitine concentrations in blood and in liver and abdominal muscle biopsy specimens in 13 men and 16 women undergoing elective surgery (mostly gallbladder removal). The data suggest that the carnitine pools of plasma and erythrocytes are different. The erythrocytes show a higher acylcarnitine concentration than does plasma (P < 0.001). Several reference bases for values in tissues have been used--dry weight, noncollagen protein (NCP), and DNA--because these may be differently influenced by disease. In liver specimens, the quotient NCP (g)/DNA (g) was significantly higher in men, 54.4 +/- 6.3 (mean +/- SD), than in women, 47.7 +/- 7.0 (P < 0.01). Liver total carnitine content in relation to DNA was significantly higher in men than in women: 0.29 +/- 0.06 vs 0.22 +/- 0.08 mmol/g DNA (P < 0.01). Free carnitine content was significantly higher in men than in women independently of the reference base, e.g., 3.7 +/- 1.0 mumol/g NCP for men vs 2.9 +/- 1.0 for women (P < 0.05). No difference was found between the sexes in the abdominal muscle carnitine content, 20.6 +/- 6.7 mumol/g NCP for men vs 17.9 +/- 5.0 for women. Our study establishes control ranges, thereby providing an important basis for studies of patients with abnormal carnitine metabolism.

Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)

Carnitine metabolism during exercise in patients on chronic hemodialysis

Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age-matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high-intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic release of carnitine: effect of increased concentration by clofibrate treatment.

The release of carnitine is an important metabolic function of the liver. In the present study, we have investigated the effect of increased carnitine concentration on the hepatic release of carnitine. Hepatic carnitine concentration was increased in rats by clofibrate treatment. Release of carnitine was investigated as its efflux from perfused liver and its secretion into bile. A significantly smaller proportion of the hepatic pool of carnitine was released into the perfusion medium when carnitine concentration was increased by clofibrate treatment. However, the amount of carnitine released (nmol/g liver) was comparable to that of control rats. Increased carnitine concentration by clofibrate treatment also did not affect the rate of biliary secretion of carnitine. In control rats, nearly 50% of the released carnitine, in both the perfusion medium and bile, was acylcarnitine whereas in clofibrate-treated rats 35% of the released carnitine was acylcarnitine. Release into the perfusion medium was the major route for the hepatic export of carnitine. We conclude that when hepatic carnitine concentration is increased by clofibrate treatment, a smaller proportion of the hepatic carnitine pool is released, but the amount of carnitine released (nmol/g liver) is not greatly different than that from control animals.

Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis

Glucose homeostasis and fatty acid metabolism are abnormal in patients with cirrhosis. To assess the metabolic response to starvation in an animal model of cirrhosis, glycogen and fuel metabolism were characterized in rats with CCl4-induced cirrhosis studied 2 wk after 10 weekly doses of CCl4. Plasma concentrations of glucose and beta-hydroxybutyrate were not different between fed CCl4-treated and control rats, but plasma nonesterified fatty acid concentrations were higher in cirrhotic animals (0.25 +/- 0.01 vs. 0.39 +/- 0.04 mmol/L; p less than 0.05). After 12 hr of starvation, the plasma nonesterified fatty acid concentration had reached 0.58 +/- 0.04 mmol/L in CCl4-treated rats, compared with 0.38 +/- 0.04 mmol/L in control rats (p less than 0.05). The redistribution of the hepatic carnitine pool toward acylcarnitines, which is characteristic of starvation, was complete after fasting for 12 hr in the CCl4-treated rats, compared with the 24 hr required in control rats. In fed cirrhotic rats, liver glycogen content per gram liver was decreased by 64% compared with control rats (30.0 +/- 5.1 vs. 10.8 +/- 1.1 mg/gm liver wet wt; p less than 0.05). After 12-hr fasting, hepatic glycogen content had fallen to 14.3 +/- 3.9 and 4.8 +/- 0.4 mg/gm liver wet wt (p less than 0.05) in control and cirrhotic animals, respectively. To further characterize the status of glycogen metabolism in cirrhotic livers, activities of glycogen synthase and glycogen phosphorylase were determined. Hepatic active and total glycogen phosphorylase activities normalized to hepatocellular content were unaffected by CCl4 treatment, whereas total glycogen synthase activity was increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Valproic Acid on Plasma Carnitine Levels

Plasma total, free, and acyl carnitine levels were determined in four groups of children: (1) those treated with valproic acid as monotherapy (n = 43), (2) those treated with valproic acid plus other antiepileptics as polytherapy (n = 91), (3) those treated with other antiepileptic drugs alone (n = 43), and (4) normal patients (n = 89). The mean free carnitine level was significantly lower in both the valproic acid monotherapy (29.9 mumol/L) and polytherapy (21.4 mumol/L) groups compared with normal subjects (36.8 mumol/L); it was also significantly lower than that in patients treated with other antiepileptic drugs (36.7 mumol/L). Comparison of valproic acid polytherapy and monotherapy yielded significantly lower free carnitine levels in the polytherapy group. The ratios of acyl to free carnitine for monotherapy (0.41) and polytherapy (0.45) were significantly higher than that in the normal group (0.25). This study indicates that a general decrease in the carnitine pool should be anticipated in patients taking valproic acid polytherapy and, to a lesser degree, monotherapy. Carnitine levels in the group taking other drugs did not differ from normal.

Effect of exogenous carnitine on carnitine homeostasis in the rat

The interaction of exogenous carnitine with whole body carnitine homeostasis was characterized in the rat. Carnitine was administered in pharmacologic doses (0-33.3 mumols/100 g body weight) by bolus, intravenous injection, and plasma, urine, liver, skeletal muscle and heart content of carnitine and acylcarnitines quantitated over a 48 h period. Pre-injection urinary carnitine excretion was circadian as excretion rates were increased 2-fold during the lights-off cycle as compared with the lights-on cycle. Following carnitine administration, there was an increase in urinary total carnitine excretion which accounted for approx. 60% of the administered carnitine at doses above 8.3 mumols/100 g body weight. Urinary acylcarnitine excretion was increased following carnitine administration in a dose-dependent fashion. During the 24 h following administration of 16.7 mumols [14C]carnitine/100 g body weight, urinary carnitine specific activity averaged only 72 +/- 4% of the injection solution specific activity. This dilution of the [14C]carnitine specific activity suggests that endogenous carnitine contributed to the increased net urinary carnitine excretion following carnitine administration. 5 min after administration of 16.7 mumol carnitine/100 g body weight approx. 80% of the injected carnitine was in the extracellular fluid compartment and 5% in the liver. Plasma, liver and soleus total carnitine contents were increased 6 h after administration of 16.7 mumols carnitine/100 g body weight. 6 h post-administration, 37% of the dose was recovered in the urine, 12% remained in the extracellular compartment, 9% was in the liver and 22% was distributed in the skeletal muscle. In liver and plasma, short chain acylcarnitine content was increased 5 min and 6 h post injection as compared with controls. Plasma, liver, skeletal muscle and heart carnitine contents were not different from control levels 48 h after carnitine administration. The results demonstrate that single, bolus administration of carnitine is effective in increasing urinary acylcarnitine elimination. While liver carnitine content is doubled for at least 6 h following carnitine administration, skeletal muscle and heart carnitine pools are only modestly perturbed following a single intravenous carnitine dose. The dilution of [14C]carnitine specific activity in the urine of treated animals suggests that tissue-blood carnitine or acylcarnitine exchange systems contribute to overall carnitine homeostasis following carnitine administration.

Lack of effect of oral L-carnitine treatment on lipid metabolism and cardiac function in chronically diabetic rats

L-Carnitine is necessary for the transfer of long-chain fatty acids into the mitochondrial matrix where energy production occurs. In the absence of L-carnitine, the accumulation of free fatty acids and related intermediates could produce myocardial subcellular alterations and cardiac dysfunction. Diabetic hearts have a deficiency in the total carnitine pool and develop cardiac dysfunction. This suggested that carnitine therapy may ameliorate alteration in cardiac contractile performance seen during diabetes. In this study, heart function was studied in streptozotocin diabetic rats given L-carnitine orally. Oral L-carnitine treatment (50-250 mg.kg-1.day-1) of 1- and 3-week diabetic rats increased plasma free and total carnitine and decreased plasma acyl carnitine levels. In both groups, myocardial total carnitine levels were increased. However, L-carnitine (200 mg.kg-1.day-1) treatment of diabetic rats for 6 weeks had no effect on plasma carnitine levels. Similarly, plasma lipids remained elevated whereas cardiac function was still depressed. These studies suggest that in the chronically diabetic rat, the route of administration of L-carnitine is an important factor in determining an effect.

Changes in muscle free carnitine and acetylcarnitine with increasing work intensity in the Thoroughbred horse

Treadmill exercise in Thoroughbred horses of 2 min duration and increasing intensity resulted in increased formation and accumulation of acetylcarnitine in the working middle gluteal muscle. At high work intensities a plateau in acetylcarnitine formation was reached corresponding to approximately 70% of the total carnitine pool (approx. 30 mmol.kg-1 dry muscle). Formation of acetylcarnitine was mirrored by an equal fall in the free carnitine content, which stabilised, at the highest work intensities, at around 8 mmol.kg-1 dry muscle. Acetylcarnitine and carnitine reached their point of maximum change at a work intensity just below that resulting in the rapid production and accumulation of lactate and glycerol 3-phosphate. It is possible that the formation of acetylcarnitine is important in the regulation of the intramitochondrial acetyl CoA/CoA ratio; equally these changes may represent a blocking mechanism aimed at preventing the transfer of unwanted free fatty acids (as acylcarnitines) into the mitochondria at work intensities where they could contribute little to energy production.

Muscle carnitine pools in cancer patients

Muscle and plasma concentrations of free and acylated carnitine (short-chain acylcarnitine and long-chain acylcarnitine) were determined by employing an optimized radiochemical-enzymatic assay in 14 healthy volunteers and in 10 patients with oesophageal carcinoma prior to elective operation. No significant correlations between total carnitine and its subfractions in muscle and plasma were observed and no sex differences were apparent. The estimated total carnitine pool in the patients (75.0 ± 27 mmol) was significantly reduced compared to controls (130 ± 24.3 mmol). The reduction was still present when expressed per kg muscle tissue (3.5 ± 1.0 mmol versus 4.5 ± 0.7 mmol) in order to consider age related decreased muscle mass in the patients. The muscular ratio of acylcarnitines to free carnitine was higher in the patients (0.23 ± 0.10) than in healthy subjects (0.15 ± 0.07), whereas the corresponding plasma quotient in the patients (0.22 ± 0.09) was lowered compared to controls (0.30 ± 0.10), indicating that instead of glucose, oxidation of fatty acids can be maintained, resulting in a preservation of the glycogen stores and thus an energy-conserving metabolic adaptation as a response to prolonged energy deficit.

Butyrobetaine availability in liver is a regulatory factor for carnitine biosynthesis in rat

Urinary excretion of total carnitine in 48-h fasted rats dropped to 0.30 +/- 0.01 mumol/day from 2.23 +/- 0.4 mumol/day found in fed, control animals (mean +/- SEM). Despite this marked retention, the total carnitine content of the whole body remained constant, about 83 mumol, predicting a slow-down in biosynthesis. The conversion of butyrobetaine into carnitine takes place only in the liver in rats. 48 h of starvation caused a decrease in the liver butyrobetaine level from 11.6 +/- 1.19 nmol/g to 9.30 +/- 1.19 nmol/g, which in whole livers corresponds to a decrease from 138 nmol to 61.3 nmol. The conversion rate of butyrobetaine into carnitine was studied with radiolabelled butyrobetaine. 30 min after injection of [3H]butyrobetaine the carnitine pool in the liver of fasted rats was labelled to about the same extent as that in fed rats, but from a butyrobetaine pool with higher specific radioactivity. Therefore, the conversion rate of butyrobetaine into carnitine was reduced. The newly formed carnitine found in the whole body of fasted rats was estimated to be 59% of controls. We conclude that the biosynthesis of carnitine in fasted rats slows down, for which a decreased availability of butyrobetaine in the liver is responsible. Urinary excretion of butyrobetaine in the fasted group decreased to 74.1 nmol/day from the 222-nmol/day control value while the butyrobetaine content of whole body did not significantly decrease (2.85 mumol vs. 3.04 mumol). Urinary excretion of trimethyllysine was also depressed.

Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state.

Carnitine metabolism has been previously shown to change with exercise in normal subjects, and in patients with ischemic muscle diseases. To characterize carnitine metabolism further during exercise, six normal male subjects performed constant-load exercise on a bicycle ergometer on two separate occasions. Low-intensity exercise was performed for 60 min at a work load equal to 50% of the lactate threshold, and high-intensity exercise was performed for 30 min at a work load between the lactate threshold and maximal work capacity for the individual. Low-intensity exercise was not associated with a change in muscle (vastus lateralis) carnitine metabolism. In contrast, from rest to 10 min of high-intensity exercise, muscle short-chain acylcarnitine content increased 5.5-fold while free carnitine content decreased 66%, and muscle total carnitine content decreased by 19% (all P less than 0.01). These changes in skeletal muscle carnitine metabolism were present at the completion of 30 min of high-intensity exercise, and persisted through a 60-min recovery period. With 30 min of high-intensity exercise, plasma short-chain and long-chain acylcarnitine concentrations increased by 46% and 23%, respectively. Neither exercise state was associated with a change in the urine excretion rates of free carnitine or acylcarnitines. Thus, alterations in skeletal muscle carnitine metabolism, characterized by an increase in acylcarnitines and a decrease in free and total carnitine, are dependent on the work load and, therefore, the metabolic state associated with the exercise, and are poorly reflected in the plasma and urine carnitine pools.

Ester composition of carnitine in the perfusate of liver and in the plasma of donor rats.

When the carnitine pool of fed rats was labelled with tritium, in non-recirculating perfusate of their liver 44% of acid-soluble 3H activity was identified as free carnitine and 47% as short-chain acylcarnitine. Of the latter component acetylcarnitine accounted for 30% and propionylcarnitine for 10% of total acid-soluble. In plasma the contribution of short-chain acylcarnitines to total carnitine in fed, fasted and diabetic rats was 15.6%, 43.1% and 48.0%, respectively. Recirculating perfusion of livers from the same animals revealed that livers from fed rats released short-chain acylcarnitines as much as 56.2% of total and this proportion did not increase further in the other two groups. At the same time, ketone bodies in the perfusate increased gradually in the fed, fasted and diabetic group, paralleling the plasma ketone levels. Although liver supplies the organism with carnitine the increment of plasma short-chain acylcarnitines seen in ketosis is not a result of some extra output by the liver.

The effects of post-exercise glucose and alanine ingestion on plasma carnitine and ketosis in humans.

1. Several studies have hypothesized that alanine decreases plasma ketone body levels by increasing availability of oxaloacetate, thus allowing acetyl groups to enter the tricarboxylic acid cycle and releasing co-enzyme A (CoA). 2. Four, fasted adult males exercised at 50% of their maximal oxygen consumption for 1.5 h, then ingested 100 g of either glucose or alanine 2 h into recovery. 3. Post-exercise ketosis had developed at 2 h into recovery, as shown by a significantly elevated concentration of beta-hydroxybutyrate in the plasma. At this time plasma free fatty acids were elevated above resting levels while plasma free carnitine concentrations had fallen below resting values. 4. After either alanine or glucose ingestion beta-hydroxybutyrate concentrations fell to the same extent. After the alanine load free carnitine increased above that seen in the glucose trial. Following either alanine or glucose ingestion free fatty acid levels fell; they remained at resting levels in the alanine trial but decreased below rest in the glucose trial. 5. We assume that plasma carnitine concentrations largely reflect the hepatic carnitine pools; therefore, elevations in the plasma free carnitine are probably the result of an increased utilization of acetyl CoA. The significant elevation in plasma free carnitine concentration found after alanine ingestion is consistent with the hypothesis that alanine increases the oxidation of acetyl CoA by providing oxaloacetate for the tricarboxylic acid cycle.

In vivo and in vitro intervention with l-carnitine prevents abnormal energy metabolism in isolated diabetic rat heart: Chemical and phosphorus-31 NMR evidence

The beneficial effects of in vivo injections (200 mg/kg, twice daily) or in vitro perfusion (5.0 mM) of L-carnitine on an intrinsic abnormality in energy metabolism was investigated in isolated, perfused diabetic rat heart. Hearts were aerobically perfused for 60 min with elevated fatty acid substrate to simulate diabetic conditions. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed a temporal decline in myocardial ATP levels (to approx 82%) during perfusion of diabetic hearts, but not in control hearts. This reduction was prevented by prior treatment in vivo with L-carnitine or by providing L-carnitine acutely in the perfusion medium. Chemical analysis of tissue extracts indicated that L-carnitine injections were effective in replenishing the decrease in total myocardial carnitine content which was present in diabetic hearts and in preventing the accumulation of long chain fatty acyl CoA. Perfusion with L-carnitine also attenuated the elevation of long chain fatty acyl CoA in diabetic hearts. This study gives additional support to the hypothesis that decreases in ATP which occur in the isolated, perfused diabetic heart are correlated with a concomitant elevation in long chain fatty acyl CoA, a known inhibitor of adenine nucleotide translocase. In the presence of elevated exogenous fatty acids, a primary deficiency in the total myocardial carnitine pool would result in elevations in tissue concentrations of long chain fatty acyl CoA since carnitine is a required carrier for transport of fatty acids into mitochondria. Replenishment of the carnitine in vivo was shown to be sufficient to prevent subsequent alteration in long chain fatty acyl CoA and ATP in isolated perfused diabetic hearts despite the burden of elevated fatty acid substrates.

Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane and it is derived from the diet and from endogenous synthesis from lysine and methionine. Of the body's carnitine pool, about 98% is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% ± 1.8 (mean ± SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% ± 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 ± 4.0 μmol/g dry weight (mean ± SD) for the surgical patients and 20.8 ± 5.0 μmol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3–5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition.

Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Carnitine is derived from the diet and from endogenous synthesis from lysine and methionine. About 98% of the body's carnitine pool is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% ± 1.8 (mean ± SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% ± 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 ± 4.0 μmol/g dry weight (mean ± SD) for the surgical patients and 20.8 ± 5.0 μmol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3–5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition.