title: The effect of propionyl L-carnitine on skeletal muscle metabolism in renal failure.
abstract: The effect of propionyl L-carnitine on skeletal muscle metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31P magnetic resonance spectroscopy we examined calf muscle metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g.p.o. daily. Resting phosphocreatine/ATP (4.41 +/- 0.20 [SEM]) decreased to normal control levels on PLC (3.98 +/- 0.14; controls 4.00 +/- 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic metabolism of muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Qmax) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/min after PLC; controls 49 +/- 3 mM/min). Qmax correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative capacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those patients (n = 6) with [Hb] > 10 g/dl. [Hb] was rate limiting to oxidative metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.
authors.affiliation: MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Thompson
authors.forename: A B
authors.initials: AB
authors.lastname: Irish
authors.forename: G J
authors.initials: GJ
authors.lastname: Kemp
authors.forename: D J
authors.initials: DJ
authors.lastname: Taylor
authors.forename: G K
authors.initials: GK
authors.lastname: Radda
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000740:Anemia / Q000209:etiology / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000627:therapeutic use; D015444:Exercise / Q000502:physiology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010725:Phosphocreatine / Q000096:biosynthesis; D006435:Renal Dialysis
chemical_list: D006454:Hemoglobins; D010725:Phosphocreatine; C003223:propionylcarnitine; D000255:Adenosine Triphosphate; D002331:Carnitine