Enzymology of the carnitine biosynthesis pathway

Abstract

SummaryThe water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides their capacity to take up carnitine from the diet or extracellular medium through plasma membrane transporters. This review discusses the current knowledge on carnitine homeostasis with special emphasis on the enzymology of the four steps of the carnitine biosynthesis pathway.

Metabolite Profiling of Bendamustine in Urine of Cancer Patients after Administration of [14C]Bendamustine

“…The high-resolution mass of the conjugate of Met17 (161.1046 Da) led to a proposed elemental composition of C 7 H 15 NO 3 (161.1046 Da; ⌬ppm ϭ Ϫ2.48), a molecular formula corresponding with that of carnitine. This quarternary ammonium compound can be endogenously formed and is required for transport of long-chain fatty acids across intracellular membranes, which is facilitated by oxidation of the fatty acids into acylcarnitines (Strijbis et al, 2010). The suggestion of Met17 being a carnitine conjugate of bendamustine is supported by the most abundant product ion at m/z 424.1624, because the loss of 59.0729 Da (loss of trimethylamine) is characteristic for carnitine and acylcarnitine conjugates (Minkler et al, 2005).…”

The Molecular and Metabolic Influence of Long Term Agmatine Consumption

“…Car biosynthesis is very limited or absent in muscle (24). Therefore, the AGM-induced increase in the muscle Car level in the HFD ϩ AGM group (Table 2) must be mediated via increased Car import.…”

“…Impact on Genes Responsible for Carnitine Biosynthesis and Transport-Car is synthesized mainly in the liver and kidney from trimethyllysine (TML) released during proteolysis (24). In an attempt to reveal the cause of the AGM-induced increase in body Car, we determined the expression of the primary genes responsible for Car biosynthesis in the liver and kidney.…”

“…A separate series of incubations was carried out in medium as described (23) to determine the activity of ␥-butyrobetaine dioxygenase (␥-BBD), the enzyme that catalyzes the last step of Car synthesis (23,24). Incubations at 37 ºC were stopped after 30 min by addition of 1 ml of methanol.…”

A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism

“…OCTN2 deficiency is characterized by excessive urinary loss of carnitine, leading to systemic deficiency with associated skeletal myopathy, cardiomyopathy, fatty liver, and hypoglycemia. Although the possibility of a primary systemic carnitine deficiency caused by a defect in carnitine biosynthesis was postulated long ago, no primary disorders of carnitine biosynthesis have been described until now (7).…”