+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

Journal of Clinical Investigation 73(3): 857-867

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 005780615

Download citation: RISBibTeXText

PMID: 6707204

Related references

Effect of carnitine deprivation on carnitine homeostasis and energy metabolism in mice with systemic carnitine deficiency. Annals of Nutrition and Metabolism 52(2): 136-144, 2008

Up-regulation of carnitine transporters helps maintain tissue carnitine levels in carnitine deficiency induced by pivalic acid. Pharmaceutical Research 18(4): 439-445, 2001

Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. European Journal of Nutrition 51(1): 1-18, 2012

Gene-dose effect on carnitine transport activity in embryonic fibroblasts of JVS mice as a model of human carnitine transporter deficiency. Biochemical Pharmacology. 55(10): 1729-1732, 10, 1998

Kinetic compartmental analysis of carnitine metabolism in the dog. Archives of Biochemistry and Biophysics 220(1): 60-70, 1983

Kinetic compartmental analysis of carnitine metabolism in the dog. Federation Proceedings 41(3): ABSTRACT 1561, 1982

Carnitine levels in skeletal muscle, blood, and urine in patients with primary carnitine deficiency during intermission of L-carnitine supplementation. Jimd Reports 20: 103-111, 2015

Effects of dietary L-carnitine and protein level on plasma carnitine, energy and carnitine balance, and carnitine biosynthesis of 20 kg pigs. Asian Australasian Journal of Animal Sciences 13(11): 1568-1575, 2000

Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers. Clinical and Investigative Medicine. Medecine Clinique et Experimentale 32(1): E13-E19, 2009

Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Human Molecular Genetics 8(4): 655-660, 1999

Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatric Research 28(3): 247-255, 1990

In vitro analysis of hepatic carnitine biosynthesis in human systemic carnitine deficiency. Clinica Chimica Acta 106(3): 295-300, 1980

Nearly fatal lipid laden myopathy with myo globinuria and myo deficiency of carnitine prednisone failure but dramatic improvement with carnitine and cultured muscle dependence on carnitine. Neurology 30(4): 368, 1980

Enhancement of mitochondrial carnitine and carnitine acyl carnitine translocase mediated transport of fatty acids into liver mitochondria under ketogenic conditions. Journal of Biological Chemistry 254(12): 5423-5429, 1979

Carnitine metabolism and human carnitine deficiency. Nutrition 9(3): 246-254, 1993