ABSTRACT
Carnitine homeostasis and the kidney-normal physiology .................... 80 Changes in carnitine homeostasis in renal failure ....................................... 82 Carnitine as a biomarker in patients on hemodialysis ............................... 85 Effect of carnitine supplementation on carnitine homeostasis in patients on hemodialysis ................................................................................ 85 Therapeutic use of carnitine in patients on hemodialysis .......................... 87 Conclusions ....................................................................................................... 90 Disclosures ........................................................................................................ 91 References .......................................................................................................... 91
Carnitine homeostasis and the kidney-normal physiology Carnitine homeostasis is complex. Carnitine is derived from both dietary sources and endogenous biosynthesis. There is no catabolism of carnitine in mammalian cells, but it is reversibly converted to acylcarnitines in reactions catalyzed by a family of carnitine acyltransferases [4, 5] (Figure 6.1). The pool of acylcarnitines will consist of a spectrum of specific compounds defined by the fatty acyl moiety attached to carnitine (for example, acetylcarnitine, propionylcarnitine, etc.). Thus, the carnitine content in a biological compartment is described by the concentrations of carnitine, each individual acylcarnitine (when not otherwise specified, “acylcarnitine concentration” refers to the sum of all individual acylcarnitine concentrations), total carnitine (the sum of carnitine and all acylcarnitines), and the distribution of the total carnitine between carnitine and acylcarnitines. The distribution of the carnitine pool between carnitine and
Figure 6.1 The reversible transfer of fatty acyl groups from coenzyme A to carnitine. The reaction shown is catalyzed by a family of carnitine acyltransferases [5] and is readily reversible conserving the energy of acyl group activation. In most tissues the reaction appears to operate near equilibrium as the distribution of acyl groups in the coenzyme A and carnitine pools is similar. This concordant redistribution of the carnitine and coenzyme A (CoA) pools is seen in human skeletal muscle during high-intensity exercise (acetlycarnitine increases from 28% to 70%, calculated as percent of the sum of carnitine + acetylcarnitine, while acetyl-CoA increases from 25% to 51%, calculated as percent of the sum of coenzyme A + acetylcarnitine, in the transition from rest to exercise at 90% of VO2max). (Data adapted from Constantin-Teodosiu et al., Acta Physiol Scand 1991;143:367-72.)
acylcarnitines is important, as the acyltransferase reaction appears to operate near equilibrium in most mammalian tissues. As a result, the distribution of a tissue’s carnitine pool reflects the status of the metabolically critical coenzyme A (CoA) pool. Thus, when a metabolic transition occurs leading to increased concentration of an acyl-CoA, the corresponding acylcarnitine will also accumulate at the expense of carnitine (Figure 6.1). This reaction is particularly important under conditions of metabolic dysfunction where generation of the acylcarnitine can lower the concentration of a potentially toxic acyl-CoA and make CoA available for other reactions [5-7].
