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EFFECTS OF INTRAVENOUSLY INFUSED CARNITINE ON BRANCHED-CHAIN AMINO ACID METABOLISM IN FASTED AND PARENTERALLY-FED RATS. J.A. Vazquez, H.S. Paul, and S.A. Adibi. Montefiore Hospital and University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A.

Our studies as well as those of others have shown that addition of carnitine to the in- cubation medium stimulates the oxidation of branched-chain amino acids (BCAA) and their ketoanalogues (BCKA) by tissue preparations. Despite a wide interest in the metabolic effects of carnitine, the physiological relevance of the above observation has not yet been investiqated. In the present experiments we have used a primed continuous infusion of [1-14C]leucine to investigate the effect of intravenously administered carnitine (34 umol/lOO q/h) on parameters of BCAA metabolism in vivo in rats. Rats were either fasted for 3 days or parenterally-fed for 7 days.

Carnitine infusion was without a significant effect on plasma concentrations of BCAA and BCKA, whole body rate of leucine oxidation, leucine turnover, and leucine incorporation into liver and muscle proteins of either fasted or fed rats. For example, whole body rates of leucine oxidation with and without carnitine in parenterally-fed rats were 2.2 + 0.3 vs 2.3 + 0.3 ~mol/lOO g/h (mean + SEM, 7 rats), respectively. In view of the importance of BCAA in protein metabolism, we also investigated the effect of carnitine infusion on nitrogen balance and protein content of the liver and muscle. Again, carni- tine infusion was without a significant effect on these parameters of protein metabolism in either starved or fed rats. Lastly, we investigated the effect of carnitine infusion on its concentration in plasma, liver, muscle, and urine. Despite a 2 to 3-fold increase in plasma carnitine level, tissue concentrations of carnitine and its acyl-derivatives were not significantly affected by carnitine infusion either in fasted or in fed rats. Of the amount of carnitine infused, 91% was lost in the urine of fasted rats and 87% in the urine of fed rats. We conclude that under our experimental conditions intravenous carnitine infusion does not affect metabolism cf protein in general, and that of BCAA in particular. This lack of effect may be related to failure to enrich tissue pools of car- nitine or to the fact that endogenous carnitine is sufficient to maintain BCAA oxidation.

IMPROVES CARNITINE-SUPPLEMENTATION DISTURBED LIPID-METABOLISM IN UREMIC CHILDREN? A.GlGggler(l), M.Bulla(Z), M.Frosch(2), E.Kuwertz-BrGking(2), P.Ftirst(l); (1) Inst. Biol. Chem. & Nutr., Univ. Hohenheim; (2) Dept. Ped. Nephrol., Univ. Miinster, FRG.

Chronic renal failure is often associated with h perlipidemia, factor for atherosclerosis. The essential role o :

which represents a risk carnitine (C) in lipid metabolism is

now well documented and a S.C. "lipid-lowering" effect is claimed following iv or oral supplementation in various pathological conditions.

The aim of the study was to evaluate lipid and C-metabolism in 7 hemodialyzed children (age; 5-17 years) before therapy (to), after 5-month supplementation with L-C (5mg/kg BW iv after each dialysis treatment) (tl) and 2 months after discontinuation of C-treatment (t2).

Plasma levels TC" (PM)

t0 (n=7) tl (n=7) t2 (n=5) controls (r&O) 45.4 + 14.8 126.3 f 31.1* 77.8 * 15.0 49.8 & 10.0

AC/FC 1.07 + 0.25 0.69 + 0.19* 0.84 i: 0.30 0.31 + 0.20 Triglycerides (TG) (mg/dl) 284 ? 120 208 ? 129 291 + 187 77 -t 16 HOL-cholesterol (mg/dI) 37.6 +_ 5.1 44.3 +_ 6.0* 44.6 +- 6.7 54.0 +_ 2.3 mean f SD; l P 5 0.05 compared to to; ' = total carnitine; = acylated to free carnitine

The pronounced increase in plasma-TC-level during supplementation was paralleled by an apparent decrease in TG and a rise in HDL-cholesterol as well as with a lowering in the pathological ratio of ACIFC. The quotient of total cholesterol and HDL-cholesterol - a risk indicator for atherosclerosis - was reduced at tl compared tot0 (4.4k1.4 vs. 5.& 1.9; p<O.O5). These beneficial effects were especially discernible in 5 patients with type IV hyperlipoproteinemia. After discontinuation of C-treatment (t2) plasma-TG-levels and the ratio AC/FC tended towards the pathological values seen before treatment (to).

In conclusion, L-carnitine-supplementation improves disturbed lipid-metabolism in uremic children and might thereby exert a favourable influence on the high risk for cardio- vascular disease in these patients.

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