Publications

• Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases.

  Eichmann T.O., Kumari M., Haas J.T., Farese R.V. Jr., Zimmermann R., Lass A., Zechner R.

  Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty aci ... >> More

  Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. The selectivity of ATGL broadens to the sn-1 position upon stimulation of the enzyme by its co-activator CGI-58. sn-1,3 DAG is the preferred substrate for the consecutive hydrolysis by hormone-sensitive lipase. Interestingly, diacylglycerol-O-acyltransferase 2, present at the endoplasmic reticulum and on lipid droplets, preferentially esterifies sn-1,3 DAG. This suggests that ATGL and diacylglycerol-O-acyltransferase 2 act coordinately in the hydrolysis/re-esterification cycle of TAGs on lipid droplets. Because ATGL preferentially generates sn-1,3 and sn-2,3, it suggests that TAG-derived DAG cannot directly enter phospholipid synthesis or activate protein kinase C without prior isomerization. << Less

  J. Biol. Chem. 287:41446-41457(2012) [PubMed] [EuropePMC]

  This publication is cited by 31 other entries.

• Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase.

  Gao J., Simon M.

  Retinoic acid influences epidermal morphology and function through its ability to control transcription. Because the circulation presents the epidermis with micromolar amounts of retinol that can be converted to retinoic acid, regulating retinol access is imperative. In keratinocytes the majority ... >> More

  Retinoic acid influences epidermal morphology and function through its ability to control transcription. Because the circulation presents the epidermis with micromolar amounts of retinol that can be converted to retinoic acid, regulating retinol access is imperative. In keratinocytes the majority of retinol is sequestered as long chain fatty acid esters. Although much has been learned about the major esterifying enzyme, little is known about the hydrolase that accesses retinol from its storage depot. Murine carboxylesterases and hormone sensitive lipase have been shown to have this activity. We found that their in vitro sensitivity to bis-p-nitrophenyl phosphate (BNPP), however, was not shared by the epidermal hydrolase activity. We therefore produced and screened two keratinocyte cDNA expression libraries and identified a previously sequenced gene (GS2) as a keratinocyte retinyl ester (RE) hydrolase insensitive to BNPP. The enzyme also catalyzes fattyacyl CoA-dependent and -independent retinol esterification. The hydrolysis reaction is greater at neutral pH, whereas the esterification reaction is greater at acidic pH. These activities are consistent with the increased RE content that accompanies epidermal maturation. In addition, this enzyme utilizes triolein as substrate and generates diacylglyceride and free fatty acid. << Less

  J. Invest. Dermatol. 124:1259-1266(2005) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• A comparative study of human GS2, its paralogues, and its rat orthologue.

  Gao J.G., Simon M.

  We have previously shown that human GS2 (hGS2) catalyzes keratinocyte retinylester and triglyceride hydrolysis. hGS2 and its rat orthologue, rGS2, are 80% homologous and share a proline insertion at residue 56 and a C-terminal truncation compared to the hGS2 paralogues. Both changes are required f ... >> More

  We have previously shown that human GS2 (hGS2) catalyzes keratinocyte retinylester and triglyceride hydrolysis. hGS2 and its rat orthologue, rGS2, are 80% homologous and share a proline insertion at residue 56 and a C-terminal truncation compared to the hGS2 paralogues. Both changes are required for hGS2 function. However, the catalytic capabilities of hGS2 are more similar to the paralogue, TTS-2.2, than to rGS2. Only hGS2 and hTTS-2.2 transfer fatty acid from triglyceride to retinol, hydrolyze retinylesters, and generate 1,3-diacylglycerol from triglycerides. Rat-human chimeras containing either the N- or C-terminus of rGS2 are without activity and single substitutions of rat for human residues cause activity loss. The differences between orthologues suggest that GS2 has a unique function in humans or has a function that is fulfilled by other enzymes in rodents. Since retinoid and triglyceride metabolites are transcription factor ligands, we expect that these enzymes will coordinately regulate epidermal homeostasis. << Less

  Biochem. Biophys. Res. Commun. 360:501-506(2007) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.