EurekaMag.com logo
+ Site Statistics
References:
52,654,530
Abstracts:
29,560,856
PMIDs:
28,072,755
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Studies on carnitine metabolism of various disorders accompanied by hyperammonemia



Studies on carnitine metabolism of various disorders accompanied by hyperammonemia



Sapporo Medical Journal 60(4): 339-350



Recently, the carnitine status of various disorders accompanied by hyperammonemia has been studied, and carnitine deficiency syndromes, secondary to a variety of genetic disorders have been found. The author measured the serum and tissue carnitine levels of various disorders accompanied by hyperammonemia. In patients with ornithine transcarbamylase (OTC) and carbamylphosphate synthetase (CPS-I) deficiencies, free carnitine levels in the serum were decreased and acylcarnitine levels were increased. These findings were also observed in liver tissues. However, the serum and hepatic carnitine concentrations of congenital hyperammonemic patients with other cytosolic enzyme deficencies of the urea cycle were within normal limits. Carnitine levels in the serum and liver tissues of some patients with OTC deficiency decreased gradually with age. In the patient with CPS-I deficiency, the man blood ammonia levels decreased significantly, accompanied by an increase in serum and urine free carnitine levels after oral administration of L-carnitine (10mg/kg/day). The serum free carnitine levels of patients receiving sodium valproate (VPA) therapy decreased and their acylcarnitine free carnitine ratios increased. There existed a definite correlation between serum free carnitine and blood ammonia. Primary cultured rat hepatocytes were used to study the effect of VPA on the levels of ammonia and urea synthesis in culture medium. The addition of VPA to the culture medium resulted in an increase of ammonia and a decrease of urea synthesis. The carnitine content of hepatocytes and citrulline synthesis by hepatocytes were also decreased following VPA addition, but OTC and CPS-I activities were unchanged. When L-carnitine was added with VPA to the medium, the levels of ammonia decreased and ureas synthesis increased. These observations indicate tht VPA-induced hyperammonemia is caused by inhibition of citrulline synthesis followed by hepatic carnitine deficiency, and suggest that L-carnitine may be effective in preventing VPA-induced hyperammonemia. In the future studies, the carnitine status in congenital hyperammonemia and VPA therapy should be investigated, since oral administration of L-carnitine may be effective in patients with secondary carnitine deficiency.

(PDF emailed within 1 workday: $29.90)

Accession: 007831275

Download citation: RISBibTeXText



Related references

Carnitine therapy and metabolism in the disorders of propionyl coenzyme a metabolism studies using proton nmr spectroscopy. Clinica Chimica Acta 204(1-3): 263-278, 1991

Hyperammonemia related to carnitine metabolism with particular emphasis on ornithine transcarbamylase deficiency. Enzyme 38(1-4): 251-255, 1987

Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy. Journal of Pediatrics 109(1): 131-134, 1986

The Effect of Carnitine Supplementation on Hyperammonemia and Carnitine Deficiency Treated with Valproic Acid in a Psychiatric Setting. Innovations in Clinical Neuroscience 12(9-10): 18-24, 2015

Carnitine acyl carnitine translocase deficiency; An important cause of hyperammonemia. Pediatric Research 45(4 PART 2): 135A, April, 1999

Pharmaceutical composition comprising carnitine or alkanoyl L-carnitine, for the prevention and treatment of diseases brought about by lipid metabolism disorders. Official Gazette of the United States Patent & Trademark Office Patents 1245(3), Apr 17, 2001

Urinary excretion of l-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of l-carnitine. Pediatric Research 18(12): 1325-1328, 1984

Pharmaceutical composition comprising L-carnitine or an alkanoyl L-carnitine in combination with a polyunsaturated fatty acid of the omega-3 series for the prevention and the treatment of lipid metabolism disorders. Official Gazette of the United States Patent & Trademark Office Patents 1210(3): 2631, May 19, 1998

L-Carnitine insufficiency in disorders of organic acid metabolism: response to L-carnitine by patients with methylmalonic aciduria and 3-hydroxy-3-methylglutaric aciduria. Journal of Inherited Metabolic Disease 7 Suppl 2: 109-110, 1984

Carnitine therapy and metabolism in the disorders of propionyl-CoA metabolism studied using 1H-NMR spectroscopy. Clinica Chimica Acta 204(1-3): 263-278, 1991

L carnitine and hyperammonemia. Goldberg, D M , E De La Morena And M Werner (Ed ) Advances in Clinical Enzymology, Vol 4 Carnitine, Enzymes And Isoenzymes in Disease; 1st European Congress on Clinical Enzymology, San Lorenzo De El Escorial, Spain, June 24-28, 1985 Viii+189p S Karger Ag: Basel, Switzerland; New York, New York, Usa Illus 111-117, 1986

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

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, 1984

Valproate-associated hyperammonemia and DL-carnitine supplement. Kobe Journal of Medical Sciences 33(3): 81-87, 1987