Oleoyl-phe metabolism

Stable Identifier
R-HSA-9673163
Type
Pathway
Species
Homo sapiens
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Extracellular PM20D1 (N-fatty-acyl-amino acid synthase/hydrolase PM20D1) catalyzes the reversible condensation of L-phenylalanine (L-phe) and oleate ((9Z)-octadecenoate) to form oleoyl-phe (N-(9Z-octadecenoyl)-L-phenylalanine) and water. In addition to the condensation of phe with oleate ((9Z)-octadecenoate) annotated here, purified human PM20D1 protein in vitro can catalyze the condensation of leucine and isoleucine with oleate and with other long-chain unsaturated fatty acids including arachidonate, with lower efficiencies. Although the reverse (hydrolysis) direction of this reaction is thermodynamically favored, expression of PM20D1 protein in mice or in cultured cells was associated with elevated levels of oleoyl-phe in serum and culture media, respectively. Treatment of cultured mouse brown adipose tissue adipocytes and of isolated mitochondria with oleoyl-phe induced uncoupled respiration independently of UCP1 (uncoupling protein 1). Photolabeling studies of isolated mitochondria identified the ADP/ATP symporters SLC25A4 and SLC25A5 as possible targets of oleoyl-phe. Consistent with these observations, expression of PM20D1 and elevated blood levels of oleoyl-phe in mice were associated with increased energy expenditure and improved glucose homeostasis. These results suggest a physiological role for PM20D1 and its condensation reaction product in thermogenesis and raise the possibility that oleoyl-phe and related molecules might have a clinical role in treatment of obesity (Long et al. 2016).

Literature References
PubMed ID Title Journal Year
27374330 The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria

Long, JZ, Svensson, KJ, Bateman, LA, Lin, H, Kamenecka, T, Lokurkar, IA, Lou, J, Rao, RR, Chang, MR, Jedrychowski, MP, Paulo, JA, Gygi, SP, Griffin, PR, Nomura, DK, Spiegelman, BM

Cell 2016
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