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PubMed1975

Androgen-dependent accumulation of carnitine by rat epididymis after injection of [3H]butyrobetaine in vivo.

After i.m. injection of [3H]butyrobetaine into rats, the accumulation of carnitine into the epididymis, prostate gland, seminal vesicles, testis and heart was studied. The concentration of radiolabeled carnitine into the cauda epididymis increased linearly with time up to 72 h after the injection of the precursor, while its level in the prostate and seminal vesicles decreased rapidly. Very low levels of carnitine were found in the testis. Castration reduced the carnitine accumulation by cauda epididymis to 6% of the control levels while treatment of castrated animals with testosterone propionate (500 mug/day) partly restored the carnitine uptake. Similar treatment with 17beta-oestradiol valerate or 17alpha-hydroxyprogesterone had no effect. Surprisingly, cyproterone acetate (5 mg/day) also significantly stimulated carnitine accumulation by the epididymis to a level above that of the castrated controls. Simultaneous injection of both cyproterone acetate and testosterone propionate to castrated animals caused an additive effect of these steroids. This indicated that cyproterone acetate in this system is working as a weak androgen. Treatment of rats with 17beta-oestradiol valerate also reduced carnitine accumulation by the cauda epididymis. This is due to suppression of pituiatry gonadotrophin secretion, since concommitant treatment with testosterone propionate (500 mug/day) caused a normalization of the carnitine uptake. Treatment of intact rats with cyproterone acetate significantly reduced the epididymal weight, but not the carnitine accumulation. 17alpha-Hydroxyprogesterone treatment had no effect either on the epididymal weight or the accumulation of the carnitine. Unilateral orchiectomy reduced the carnitine accumulation by the cauda epididymis to about 40% of that occurring in the non-operated control side. This indicates that the luminal contact between the testis and epididymis or the luminal content of the epididymis itself is of importance for the androgen-dependent metabolic process occurring in the cauda epididymis. Castration or hormone treatment did not change the conversion of butyrobetaine to carnitine, or the carnitine uptake by heart. Carnitine uptake by the testis after [3H]butyrobetaine injection was rather low and this would exclude the possibility of synthesis of carnitine in the testis as a source of epididymal carnitine. Carnitine only accumulated in the cauda epididymis in vivo 4 to 96 h after injection of [3H]butyrobetaine. The presence of radioactively labeled butyrobetaine or methylcholine was not detected.

Animals↗
PubMed1979

Uptake and esterification of circulating carnitine by aorta and heart in rabbits in vivo.

Disappearance of intravenously injected DL-[methyl-14C]carnitine from the bloodstream and its uptake and esterification by heart and aorta were studied in rabbits fed atherogenic or non-atherogenic control diets. The disappearance rate of [14C]carnitine from the bloodstream was approximately 2-fold greater in animals fed the control diet than in those fed the atherogenic diets. No evidence was found for carnitine esterification in the blood. Circulating [14C]carnitine was taken up and esterified in both the heart and aorta of all animals regardless of diet; however, on comparing dpm/mg lipid-free dry weight, uptake of [14C]carnitine and accumulation of [14C]carnitine esters by the heart was greater (6-fold and 12-fold, respectively) than by the aorta. Analysis of defined arterial segments indicated that aortas in animals fed the atherogenic diet contained greater [14C]carnitine activity (4- to 8-fold) and greater acetyl-[14C]carnitine activity (4-fold) when compared to aortas of control animals; uptake of plasma [14C]carnitine and accumulation of acyl-[14C]carnitine compounds by the heart was independent of diet. Butyryl-[14C]carnitine, although not detected in aortas from animals fed the non-atherogenic or atherogenic diet for only 7 weeks, was detected in aortas from animals fed the atherogenic diet 17 weeks. Butyryl-[14C]carnitine was detected in heart tissue regardless of the animals' dietary regime. The increased uptake of circulating [14C]carnitine and its accumulation as both free and esterfied carnitine in atherosclerotic aortas occurred before the development of extensive macroscopic atherosclerotic lesions; this response of the aorta to atherogenic stimuli was not a general tissue response in that the heart did not respond similarly. Since blood carnitine is found predominantly in the plasma fraction, it is likely that these results refect the uptake and metabolism of plasma carnitine in vivo.

Animals↗
PubMed1978

Variation in tissue carnitine concentrations with age and sex in the rat.

Diabetes, starvation and various hormonal treatments are known to alter drastically carnitine concentrations in the body. Before the mechanisms controlling carnitine metabolism could be determined, it was necessary to establish normal carnitine concentrations in both sexes at different ages. Carnitine was assayed in plasma, liver, heart and skeletal muscle of rats from birth to weaning. The plasma carnitine increased rapidly during the first 2 days after birth. Carnitine in both heart and skeletal muscle increased, whereas liver concentrations declined during the first week of life. A carnitine-free diet containing sufficient precursors for carnitine biosynthesis was fed to weanling rats. Groups of ten male and ten female rats were killed each week for 10 consecutive weeks. Carnitine was determined in plasma, liver, heart, skeletal muscle, urine and epididymis in the male. There was no difference in carnitine concentrations between the sexes at weaning. Plasma, heart and muscle concentrations were higher in adult male rats than in adult females. However, liver carnitine and urinary carnitine concentrations were higher in adult female than in adult male rats. The epididymal carnitine concentration increased very rapidly during 50 to 70 days of age and the differences in carnitine concentrations between the sexes also became apparent during this time. Thus both the age and the sex of the human subject or experimental animal must be considered when investigating carnitine metabolism.

Age Factors↗
PubMed1978

Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle.

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.

Amino Acids↗
PubMed1978

Altered tissue carnitine levels in animals with hereditary muscular dystrophy.

Low levels of muscle carnitine have been found in patients with Duchenne dystrophy, a case possibly of Becker dystrophy, and limb-girdle syndrome as well as in patients with the recently described muscle carnitine deficiency syndrome. Tissues of the mouse, hamster, and chicken were analyzed to determine whether tissue carnitine levels were altered in the animal models of muscular dystrophy. Significantly higher levels of carnitine were found in dystrophic mouse muscle, but carnitine levels in plasma, liver and heart were normal. Histological changes in the skeletal muscle of dystrophic hamsters were relatively mild, and both skeletal muscle and plasma levels were normal. The liver carnitine level was higher than normal levels. The dystrophic hamster also had an inherited cardiomyopathy, and interestingly its heart carnitine level was much lower than normal. The red muscle of the normal chicken contained 5 times the level of carnitine found in white muscle. The dystrophic chicken had higher than normal levels of carnitine in the white muscle, but normal levels in the red muscle. Although all 3 animal models of muscular dystrophy studied have altered levels of carnitine in some tissue, none of the animal models had the same pattern of altered tissue carnitine levels seen in human patients.

Animals↗
PubMed1979

Muscle carnitine deficiency. Genetic heterogeneity.

Two types of lipid storage myopathy have been associated with decreased content of carnitine in muscle. In "muscle carnitine deficiency", carnitine concentration is normal in serum, but reduced in muscle. In "systemic carnitine deficiency", apparently due to imparied synthesis of carnitine in the liver, carnitine content is low in both serum and muscle. We studied a woman with a corticosteroid-responsive, probably autosomal recessive, lipid storage myopathy. Carnitine therapy was ineffective and carnitine failed to correct the impaired fatty acid oxidation in muscle homogenates, in contrast to a previous case. Carnitine transport into skeletal muscle was normal. These observations suggest that ll cases of "muscle carnitine deficiency are not the same.

Adult↗
PubMed1979

Familial carnitine deficiency. A fatal case and subclinical state in a sister.

A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked.

Adenosine Triphosphatases↗
PubMed1978

[14C]palmitate uptake in isolated rat liver mitochondria: effects of fasting, diabetes mellitus, and inhibitors of carnitine acyltransferase.

The rapid association of Na-[16-(14)C]palmitate with isolated rat liver mitochondria was measured by an oil separation method. This association was time and temperature-dependent and was absolutely dependent on the presence of exogenous ATP and CoASH and partially dependent on exogenous carnitine. Carnitine dependence was enhanced at lower concentrations of [(14)C]palmitate. At 6.5 micro M [(14)C]palmitate (molar ratio of palmitate to albumin equal to 0.54), the rate of association was linear for 20 sec and was increased more than 100% in the presence of carnitine. Carnitine-dependent association was inhibited by 2-bromopalmitate, an inhibitor of carnitine acyltransferase I, but not by (+)-octanoylcarnitine, a presumed inhibitor of carnitine acyltransferase II. The association of [(14)C]palmitate with mitochondria was enhanced from 190 to 330% in mitochondria isolated from fasted animals and from 160 to 230% in mitochondria isolated from diabetic, ketotic animals as compared to control animals. The enhanced association with mitochondria from fasted animals was inhibited by 2-bromopalmitate. These studies demonstrate a method of evaluating fatty acid association with mitochondria which, because of its dependence on carnitine and carnitine acyltransferase I activity, most likely represents true uptake into mitochondria. Furthermore, these studies indicate that the carnitine-dependent uptake of fatty acids into mitochondria is enhanced in the two ketotic states evaluated and that the carnitine acyltransferase system may be a regulatory site in ketone body production.

Acyltransferases↗
PubMed1978

[Interrelationships between carnitine metabolism and fatty acid assimilation in Pseudomonas putida (author's transl)].

The carnitine metabolism and some relations to the fatty acid metabolism were studied in Pseudomonas putida by means of control of growth, analysis of metabolites, and determination of enzyme activites. The strain grew on gamma-butyrobetaine, D,L- and L-carnitine, glycinebetaine, choline, D,L-norcarnitine, D,L-gamma-amino-beta-hydroxybutyrate, and D,L-beta-hydroxybuty-rate. Although the strain used straight-chain fatty acids of 2-16 C-atoms, it was only able to grow on O-acyl-L-carnitines of 10 or more C-atoms in the acyl-group. Addition of carnitine stimulated the growth on long-chain fatty acis. The formation of trimethylamine increased, if L-carnitine or gamma-butyrobetaine were the only carbon sources, and decreased, if these trimethylammonium compounds were carbon as well as nitrgen sources. L-Carnitine induced the carnitine dehydrogenase as well as the beta-hydroxybutyrate dehydrogenase, gamma-Butyrobetaine as carbon and nitrogen source induced the carnitine dehydrogenase, too. In the crude extract the specific activiteis of beta-hydroxybutyrate dehydrogenase were 0.7 or 1.6 mumoles.min-1.mg-1 after growth on L-carnitine and D,L-beta-hydroxybutyrate, respectively. The synthesis of both enzymes was repressed by glycinebetaine, glucose and long-chain fatty acis. Dependent on the nitrogen source L-carnitine was catabolized via two different pathways.

Animals↗
PubMedDate not supplied

Accumulation of carnitine in rat epididymis after injection of [3H]butyrobetaine in vivo: quantitative aspects, and the effects of androgens and antiandrogens.

After i.m. injection of [3H]butyrobetaine into intact and castrated rats, the specific activity of plasma carnitine remained nearly constant over 24--96 h and epididymal uptake of carnitine was constant per unit time up to 72 h. The uptake ratio of intact to castrated rats was high at 48, 72 and 96 h after injection. Administration of estradiol valerate over 20 days reduced carnitine uptake in epididymis. This reduction was dose-dependent when estrogen was administered i.m. at 0.33--10 microgram/day levels. A maximum reduction of 90% was obtained with the 10 microgram dose. A dose increase from 33 to 100 microgram/day caused no further reduction. Norspiroxenone (2--10 mg/day) and SK 7670 (1.5 and 7.5 mg/day) were less effective than estradiol valerate (10 microgram/day) in suppressing carnitine uptake in epididymis. Epididymal carnitine uptake in estradiol valerate treated rats (33 microgram/day for 20 days) increased in a time- and dose-dependent manner under testosterone propionate treatment (50, 250, 1250 microgram/day). Carnitine uptake increased to 80% of the nonsuppressed levels when testosterone propionate was adminsitered over a 6-day period at 1250 microgram/day. Dihydrotestosterone increased epididymal carnitine uptake to the same extent as testosterone propionate. delta4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol (50 microgram/day) were less effective, stimulating uptake to only 15% and 40% respectively of the testosterone propionate (250 microgram/day) stimulated levels. Changes in epididymal carnitine uptake evoked by various experimental procedures were closely paralleled by weight changes in the ventral prostate. This response resemblance indicates a similarity between the androgen sensitivity of the prostate gland and that of the carnitine uptake system in epididymis. The dose-dependent effect of estrogen on the accumulation of epididymal carnitine, together with the marked responses induced in this system by manipulation of its androgen status, support a possible use for the system as an assay for androgen or antiandrogen potency in vivo.

Androgen Antagonists↗
PubMed1978

Active transport of carnitine into skeletal muscle.

Skeletal muscle carnitine concentration exceeds plasma carnitine concentration. To determine whether this concentration gradient is maintained by active transport we studied rat soleus and extensor digitorum longus muscles. Observations consistent with the existence of an active transport mechanism were that the soleus accumulated carnitine linearly for 3 hours of incubation to exceed a distribution ratio of 1; the temperature coefficient for carnitine accumulation between 33 degrees C and 43 degrees C was 2.0; anaerobic incubation reduced carnitine accumulation by 30 percent; and the rate of carnitine accumulation was saturated at high substrate concentrations and competitively inhibited by gamma-butyrobetaine. The Km for carnitine of the carnitine transport mechanism of the soleus muscle was 0.259 mM and of the extensor digitorum longus muscle, 0.585 mM. The greater affinity of the soleus transport mechanism may explain the difference in carnitine transport by red and white muscle in intact animals. A defect in active transport of carnitine may be involved in the pathogenesis of some human myopathies characterized by excessive lipid storage and in diphtheritic cardiomyopathy.

Animals↗
PubMed1979

Hepatic ketogenesis and muscle carnitine deficiency.

The levels of plasma free carnitine and ketone bodies have been found to fluctuate inversely in fasting individuals without muscle disease. Circulating short-chain acyl-carnitines paralleled beta-hydroxybutyrate levels. A patient with lipid storage myopathy and muscle carnitine deficiency, and his two daughters, developed exaggerated ketogenesis on fasting. The content of total carnitines in the patient's liver was normal, but free carnitine was reduced to 50 percent, and total esterified carnitines were four times greater than the mean value for the controls. The decreased muscle carnitine content in this case may have resulted from chronic hepatic ketogenesis, draining muscle carnitine. Alternatively, decreased muscle carnitine content may have initiated hepatic ketogenesis.

Acetoacetates↗
PubMed1979

Effects of carnitine in ischemic and fatty acid supplemented swine hearts.

FREE FATTY ACIDS (FFA) IN EXCESS FFA: albumin molar ratios have been determined to additionally compromise mechanical performance in ischemic hearts. Carnitine, an intracellular carrier of FFA and an agent which is lost to the heart during ischemia, has been postulated to in part restore function with its replacement. To test whether its benefits are also operative in a setting of excess FFA, these studies were performed. In the main protocol, four groups of perfused swine hearts (n = 45) were compared during 50 min of control flow (179.7 ml/min) and 40 min of global ischemia (106.1 ml/min). Initial base-line serum FFA:albumin molar ratios and carnitine levels in all groups were 1.3:1 and 8.5 nmol/ml, respectively. In two of these groups FFA:albumin ratios were increased to 5.9:1 with constant infusions of Intralipid. In two alternate groups (one with and one without extra FFA supplements) dl-carnitine was supplied, sufficient to increase serum levels nearly 200-fold. Ischemia per se in 14 hearts significantly decreased several parameters of global and regional mechanical function including left ventricular (LV) and mean aortic pressures, LV isovolumetric pressure development (max dp/dt), LV epicardial motion, and LV work, together with concomitant decreases in myocardial oxygen consumption. Elevated FFA in 12 hearts rendered similarly ischemic further decreased mechanical function (LV pressure: -20.8%, P < 0.05; mean aortic pressure -26.9%, P < 0.05; LV max dp/dt: -39%, P < 0.05; regional LV shortening: -51.1%, P < 0.05; and LV work: -50.3%, P < 0.05) as compared with nonsupplemented hearts. dl-Carnitine treatments in nine hearts, not supplemented with extra FFA were without apparent effect in improving overall hemodynamic performance. However, dl-carnitine in 10 high FFA-ischemic hearts effected several improvements as compared with the untreated group: LV pressure was increased 25.6%, P < 0.025; mean aortic pressure: +43.5%, P < 0.05; LV max dp/dt: +41.5%, P < 0.05; regional LV shortening: +241.3%, P < 0.001; and LV work: +76.2%, P < 0.05 at comparable levels of myocardial oxygen consumption. In a separate protocol, the effects of stereospecificity were also studied by comparing l- with dl-carnitine in globally perfused, palmitate-supplemented hearts (five hearts in each treatment group). At similar conditions of flow and serum FFA, changes in mechanical function were comparable, except for a tendency to perform greater LV work at reduced flows in the l-carnitine-treated hearts. Thus, it was demonstrated that carnitine in ischemic hearts is capable of preserving mechanical function under conditions of excess FFA, presumably by modifying the toxic effects of FFA intermediates. The major therapeutic actions appeared to derive from the l-isomer of carnitine.

Adenosine Triphosphate↗
PubMed1978

Effect of a lipid load on blood and urinary carnitine in man.

Blood and urine carnitine contents have been determined in patients before and after a lipid load and in patients on haemodialysis. Oral and intravenous lipid administration significantly depressed blood carnitine content and after 500 ml intravenous Intralipid urinary carnitine excretion fell by 43%. Blood carnitine was reduced by 50% by haemodialysis and returned to the pre-dialysis value within 20 h in 5 out of 8 patients. It is concluded that the blood carnitine level is normally controlled over a narrow range. The fall in blood carnitine concentration and urine excretion which follows a lipid load indicate a limiting role for carnitine in lipid utilization in man, and suggest that carnitine supplements could be of value during parenteral nutrition with fats.

Administration, Oral↗
PubMed1978

Effect of fasting on free and esterified carnitine levels in human serum and urine: correlation with serum levels of free fatty acids and beta-hydroxybutyrate.

Serum levels of free L-carnitine, acylcarnitines, creatinine, beta-hydroxybutyrate, free fatty acids, cholesterol, triglycerides, and glucose were determined in healthy volunteers during a 24-36-hr fast. The effect of oral administration of free L-carnitine (1 g/person) on these parameters was studied. Urinary excretion of carnitine and creatinine was monitored throughout. Serum and urine levels of free carnitine and its renal clearance decreased during the fast. However, the serum concentration and urinary excretion of acylcarnitines increased during the same interval. Following the ingestion of free L-carnitine, both serum and urinary levels of free L-carnitine rose. Within 6 hr of ingestion, 10% of the administered dose could be accounted for by urinary excretion. No significant effect on the other serum constituents under study was seen following the oral L-carnitine dose. A significant negative correlation was found between serum levels of free L-carnitine and beta-hydroxybutyrate and free fatty acids (r equal -0.567, p less than 0.001 and r equal -0.607, p less than 0.001, respectively) during the fast.

Acetylcarnitine↗
PubMed1979

Uptake of 3H-L-carnitine by isolated rat epididymal tubules.

The uptake of radiolabeled L-carnitine has been studied in isolated epididymal tubules from the rat. The uptake of 3H-L-carnitine increases with a temperature coefficient KT of 0.22 nmol carnitine.mg protein-1 in the intermal 22--31 degrees and with a low uptake at 4 degrees C. The uptake of radiolabeled carnitine (as percent) is reduced at high concentrations of L-carnitine, by deoxycarnitine but not by D-carnitine. This uptake mechanism is especially active in the distal caput and corpus segments of the epididymis. Thus, an uptake mechanism for carnitine is present in the epididymal cells which besides the carnitine uptake in spermatozoa is responsible for the dramatic increase in carnitine concentration in cauda epididymis.

Animals↗
PubMed1979

[Clinical, morphological and biochemical studies on muscle carnitine deficiency (author's transl)].

This report deals with two sisters who died with eight, respectively ten weeks under the signs of respiratory failure caused by progressive muscular weakness. Only an elevated cerebrospinal fluid protein was suspicious of an additional disturbance of the central nervous system. Muscle biopsy revealed a vacuolar myopathy. Histochemistry showed lipid storage, increased mitochondrial enzyme activity, and to a lower degree, glycogen accumulation especially in type I muscle fibers. Electron microscopy confirmed elevated lipid content in combination with increased, enlarged and abnormally structured mitochondria. Biochemical studies on muscle biopsy, in comparison with normal children, showed a significant decrease of carnitine content and an increased activity of carnitine palmityltransferase. Retrospectively from a clinical point of view this disease is suggestive of "systemic carnitine deficiency", even if some symptoms (hepatomegaly, cardiomyopathy) were not present and serum- and liver carnitine was not measured because the children died before the diagnosis of muscle carnitine deficiency was confirmed. The clinical picture of these two fatal cases is compared with another observation of muscle caritine deficiency. This child shows only a mild course of muscle disorder, but very similar morphological changes in muscle biopsy. Biochemically, there was a clear decrease in muscular carnitine, while the serum levels were in the normal range. The activity of muscular carnitine palmityltransferase was also normal.

Biopsy↗
PubMed1978

Carnitine-acylcarnitine translocase. Inhibition by alpha-cyano-4-hydroxycinnamate and evidence for separate identity from the pyruvate transporting system of mitochondria.

Some of the known inhibitors of pyruvate transport inhibited the activity of carnitine-acylcarnitine translocase. Their order of effectiveness with millimolar concentration required for 50% inhibition given in parentheses, was: Compound UK-5099 (alpha-cyano-beta-(1-phenylindol-3-yl)acrylate) (0.1); alpha-cyano-4-hydroxycinnamate (0.17); alpha-cyano-3-hydroxycinnamate (1); alpha-cyanocinnamate (1); alpha-fluorocinnamate (7); transcinnamate (10); p-hydroxycinnamate (10); phenylpyruvate (22); p-hydroxyphenylpyruvate (25). Kinetically, the alpha-cyano-4-hydroxycinnamate inhibition was mixed and the p-hydroxyphenylpyruvate inhibition was noncompetitive with respect to external (-)-carnitine. The alpha-cyano-4-hydroxycinnamate inhibition was reversible and resulted from its ability to act as a thiol reagent. In general, alpha-cyanocinnamate and its derivatives inhibit carnitine transport at concentrations 100 to 5000 times as high as those known to pyruvate transport. At millimolar concentrations, alpha-cyano-4-hydroxycinnamate inhibited the mitochondrial transport of molecules other than carnitine as well as the activity of carnitine acyltransferases. Pyruvate and carnitine did not complete for transport into and out of mitochondria. These results establish that transmitochondrial transport mechanisms for carnitine and pyruvate involve different carriers.

Acyltransferases↗