Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

Abstract

Objective. To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies.Methods. Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed.Results. Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes.Conclusion. Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.Idiopathic inflammatory myopathies are a heterogeneous group of chronic inflammatory muscle disorders characterized by proximal muscle weakness, increased serum concentrations of creatine kjnase (CK), typical clectromyographic (EMG) changes, and mononuclear cell infiltration, with necrosis and regeneration of myocytes seen on muscle biopsy (1). Carnitine (p- hydroxy-y-trimethylammonium butyrate) is an intracellular constituent with essential metabolic functions, mainly for skeletal muscle, which uses fatty acids for its energy needs. In plasma and tissues, carnitine is present in free and esterified forms. Long-chain acylcarnitines and short-chain acylcarnitines result from the esterification of free carnitine with acyl-and acetyl-coenzyme A (CoA) groups. Carnitine regulates the transport of fatty acids across the inner mitochondrial membrane and modulates the intracellular acy1CoA:free CoA ratio (2,3) (Figure 1). It also enhances P-oxidation of longchain fatty acids, stimulates the respiratory chain, and interacts with membrane phospholipids (2-7). Thus, carnitine insufficiency could produce wide metabolic derangement and impairment of muscle function.In patients with primary mitochondrial myopathies (5,8,9) or zidovudine-induced mitochondrial myopathy (lo), muscle carnitine insufficiency is associated with mitochondrial dysfunction. We have previously reported histochemical signs of mitochondrial proliferation and respiratory chain defects in patients with inflammatory myopathies. It was proposed that these and perhaps other metabolic derangements could contribute to muscle weakness (11). To further explore other relevant metabolic alterations in patients with inflammatory myopathies, we have now studied the levels of free carnitine and carnitine esters in muscle from 13 patients. PATIENTS AND METHODSThirteen consecutive patients who were seen at the Hospital Doce de Octubre and for whom muscle biopsy specimens were available were studied. The group consisted of 7 women and 6 men, with a mean age at biopsy of 43 years (range 16-72 years). All met the Bohan and Pcter criteria for the diagnosis of polymyositis (PM) or dermatomyositis (DM) (12). Clinically, all had proxi...

L- and DL-carnitine induce tetanic fade in rat neuromuscular preparation

“…Since it is an important metabolic substance, carnitine facilitates burning of fatty acids as well as the mitochondrial transport of long-chain fatty acids, which, in turn, are important for ß-oxidation (11)(12)(13). Carnitine is structurally similar to choline, a substrate for acetylcholine synthesis (14,15), and has been used as a supplemental agent to increase performance in cardiovascular and renal diseases (16,17) and in lipid storage myopathies associated with muscle fatigue and low carnitine content in skeletal muscle (18)(19)(20). Carnitine is found in L-and Disomeric forms, but only its L-isomeric form has been described as active (5)(6)(7)(8)(9)(10).…”

Genetic risk factors associated with lipid‐lowering drug‐induced myopathies

“…20 The mechanisms of lipid-lowering drug-induced myotoxicity are unknown although there has been considerable speculation in this regard. 3,4,46 Few reports exist regarding associations with inherited 5,11,29 and acquired metabolic myopathies 2 or with peripheral neuropathies. 17,40 We suggest that a substantially larger number of individuals than expected in the general population with lipid-lowering drug-induced myopathies will have underlying metabolic myopathies triggered by the drugs.…”