Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

My Ngan Duong; Maria Psaltis; Daniel J. Rader; Dawn Marchadier; Philip J. Barter; Kerry Anne Rye

doi:10.1021/bi034990n

Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

My Ngan Duong, Maria Psaltis, Daniel J. Rader, Dawn Marchadier, Philip J. Barter, Kerry Anne Rye

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Hepatic lipase (HL) and endothelial lipase (EL) are both members of the triglyceride lipase gene family. HL hydrolyzes phospholipids and triglycerides in triglyceride-rich lipoproteins and high-density lipoproteins (HDL). EL hydrolyzes HDL phospholipids and has low triglyceride lipase activity. The aim of this study was to determine if HL and EL hydrolyze different HDL phospholipids and whether HDL phospholipid composition regulates the interaction of EL and HL with the particle surface. Spherical, reconstituted HDL (rHDL) containing either 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC), 1-palmitoyl-2-arachidonylphosphatidylcholine (PAPC), or 1-palmitoyl-2-docosahexanoylphosphatidylcholine (PDPC) as the only phospholipid, apolipoprotein A-I as the only apolipoprotein, and either cholesteryl esters (CE) only or mixtures of CE and triolein (TO) in their core were prepared. The rHDL were similar in size and had comparable core lipid/apoA-I molar ratios. The CE-containing rHDL were used to determine the kinetics of HL- and EL-mediated phospholipid hydrolysis. For HL the V_max of phospholipid hydrolysis for (POPC)rHDL > (PLPC)rHDL ∼ (PDPC)rHDL > (PAPC)rHDL, while the K_m(app) for (POPC) rHDL > (PDPC)rHDL > (PLPC)rHDL > (PAPC)rHDL. For EL the V_max for (PDPC)rHDL > (PAPC)rHDL > (PLPC)rHDL ∼ (POPC)rHDL, while the K_m(app) for (PAPC)rHDL ∼ (PLPC)rHDL > (POPC)rHDL > (PDPC)rHDL. The kinetics of EL- and HL-mediated TO hydrolysis was determined using rHDL that contained TO in their core. For HL the V_max of TO hydrolysis for (PLPC)rHDL > (POPC)rHDL > (PAPC)rHDL > (PDPC)rHDL, while the K_m(app) for (PLPC)rHDL > (POPC)rHDL ∼ (PAPC)rHDL > (PDPC)rHDL. For EL the V_max and K_m(app) for (PAPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (POPC)rHDL. These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids.

Original language	English
Pages (from-to)	13778-13785
Number of pages	8
Journal	Biochemistry
Volume	42
Issue number	46
DOIs	https://doi.org/10.1021/bi034990n
Publication status	Published or Issued - 25 Nov 2003
Externally published	Yes

ASJC Scopus subject areas

Biochemistry

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10.1021/bi034990n

Cite this

@article{31f382af43114a81a104398e76fdcc71,

title = "Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids",

abstract = "Hepatic lipase (HL) and endothelial lipase (EL) are both members of the triglyceride lipase gene family. HL hydrolyzes phospholipids and triglycerides in triglyceride-rich lipoproteins and high-density lipoproteins (HDL). EL hydrolyzes HDL phospholipids and has low triglyceride lipase activity. The aim of this study was to determine if HL and EL hydrolyze different HDL phospholipids and whether HDL phospholipid composition regulates the interaction of EL and HL with the particle surface. Spherical, reconstituted HDL (rHDL) containing either 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC), 1-palmitoyl-2-arachidonylphosphatidylcholine (PAPC), or 1-palmitoyl-2-docosahexanoylphosphatidylcholine (PDPC) as the only phospholipid, apolipoprotein A-I as the only apolipoprotein, and either cholesteryl esters (CE) only or mixtures of CE and triolein (TO) in their core were prepared. The rHDL were similar in size and had comparable core lipid/apoA-I molar ratios. The CE-containing rHDL were used to determine the kinetics of HL- and EL-mediated phospholipid hydrolysis. For HL the Vmax of phospholipid hydrolysis for (POPC)rHDL > (PLPC)rHDL ∼ (PDPC)rHDL > (PAPC)rHDL, while the Km(app) for (POPC) rHDL > (PDPC)rHDL > (PLPC)rHDL > (PAPC)rHDL. For EL the Vmax for (PDPC)rHDL > (PAPC)rHDL > (PLPC)rHDL ∼ (POPC)rHDL, while the Km(app) for (PAPC)rHDL ∼ (PLPC)rHDL > (POPC)rHDL > (PDPC)rHDL. The kinetics of EL- and HL-mediated TO hydrolysis was determined using rHDL that contained TO in their core. For HL the Vmax of TO hydrolysis for (PLPC)rHDL > (POPC)rHDL > (PAPC)rHDL > (PDPC)rHDL, while the Km(app) for (PLPC)rHDL > (POPC)rHDL ∼ (PAPC)rHDL > (PDPC)rHDL. For EL the Vmax and Km(app) for (PAPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (POPC)rHDL. These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids.",

author = "Duong, {My Ngan} and Maria Psaltis and Rader, {Daniel J.} and Dawn Marchadier and Barter, {Philip J.} and Rye, {Kerry Anne}",

year = "2003",

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day = "25",

doi = "10.1021/bi034990n",

language = "English",

volume = "42",

pages = "13778--13785",

journal = "Biochemistry",

issn = "0006-2960",

publisher = "American Chemical Society",

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T1 - Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

AU - Duong, My Ngan

AU - Psaltis, Maria

AU - Rader, Daniel J.

AU - Marchadier, Dawn

AU - Barter, Philip J.

AU - Rye, Kerry Anne

PY - 2003/11/25

Y1 - 2003/11/25

N2 - Hepatic lipase (HL) and endothelial lipase (EL) are both members of the triglyceride lipase gene family. HL hydrolyzes phospholipids and triglycerides in triglyceride-rich lipoproteins and high-density lipoproteins (HDL). EL hydrolyzes HDL phospholipids and has low triglyceride lipase activity. The aim of this study was to determine if HL and EL hydrolyze different HDL phospholipids and whether HDL phospholipid composition regulates the interaction of EL and HL with the particle surface. Spherical, reconstituted HDL (rHDL) containing either 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC), 1-palmitoyl-2-arachidonylphosphatidylcholine (PAPC), or 1-palmitoyl-2-docosahexanoylphosphatidylcholine (PDPC) as the only phospholipid, apolipoprotein A-I as the only apolipoprotein, and either cholesteryl esters (CE) only or mixtures of CE and triolein (TO) in their core were prepared. The rHDL were similar in size and had comparable core lipid/apoA-I molar ratios. The CE-containing rHDL were used to determine the kinetics of HL- and EL-mediated phospholipid hydrolysis. For HL the Vmax of phospholipid hydrolysis for (POPC)rHDL > (PLPC)rHDL ∼ (PDPC)rHDL > (PAPC)rHDL, while the Km(app) for (POPC) rHDL > (PDPC)rHDL > (PLPC)rHDL > (PAPC)rHDL. For EL the Vmax for (PDPC)rHDL > (PAPC)rHDL > (PLPC)rHDL ∼ (POPC)rHDL, while the Km(app) for (PAPC)rHDL ∼ (PLPC)rHDL > (POPC)rHDL > (PDPC)rHDL. The kinetics of EL- and HL-mediated TO hydrolysis was determined using rHDL that contained TO in their core. For HL the Vmax of TO hydrolysis for (PLPC)rHDL > (POPC)rHDL > (PAPC)rHDL > (PDPC)rHDL, while the Km(app) for (PLPC)rHDL > (POPC)rHDL ∼ (PAPC)rHDL > (PDPC)rHDL. For EL the Vmax and Km(app) for (PAPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (POPC)rHDL. These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids.

AB - Hepatic lipase (HL) and endothelial lipase (EL) are both members of the triglyceride lipase gene family. HL hydrolyzes phospholipids and triglycerides in triglyceride-rich lipoproteins and high-density lipoproteins (HDL). EL hydrolyzes HDL phospholipids and has low triglyceride lipase activity. The aim of this study was to determine if HL and EL hydrolyze different HDL phospholipids and whether HDL phospholipid composition regulates the interaction of EL and HL with the particle surface. Spherical, reconstituted HDL (rHDL) containing either 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-linoleoylphosphatidylcholine (PLPC), 1-palmitoyl-2-arachidonylphosphatidylcholine (PAPC), or 1-palmitoyl-2-docosahexanoylphosphatidylcholine (PDPC) as the only phospholipid, apolipoprotein A-I as the only apolipoprotein, and either cholesteryl esters (CE) only or mixtures of CE and triolein (TO) in their core were prepared. The rHDL were similar in size and had comparable core lipid/apoA-I molar ratios. The CE-containing rHDL were used to determine the kinetics of HL- and EL-mediated phospholipid hydrolysis. For HL the Vmax of phospholipid hydrolysis for (POPC)rHDL > (PLPC)rHDL ∼ (PDPC)rHDL > (PAPC)rHDL, while the Km(app) for (POPC) rHDL > (PDPC)rHDL > (PLPC)rHDL > (PAPC)rHDL. For EL the Vmax for (PDPC)rHDL > (PAPC)rHDL > (PLPC)rHDL ∼ (POPC)rHDL, while the Km(app) for (PAPC)rHDL ∼ (PLPC)rHDL > (POPC)rHDL > (PDPC)rHDL. The kinetics of EL- and HL-mediated TO hydrolysis was determined using rHDL that contained TO in their core. For HL the Vmax of TO hydrolysis for (PLPC)rHDL > (POPC)rHDL > (PAPC)rHDL > (PDPC)rHDL, while the Km(app) for (PLPC)rHDL > (POPC)rHDL ∼ (PAPC)rHDL > (PDPC)rHDL. For EL the Vmax and Km(app) for (PAPC)rHDL > (PDPC)rHDL > (PLPC)rHDL > (POPC)rHDL. These results establish that EL and HL have different substrate specificities for rHDL phospholipids and that their interactions with the rHDL surface are regulated by phospholipids.

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DO - 10.1021/bi034990n

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JO - Biochemistry

JF - Biochemistry

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ER -

Evidence That Hepatic Lipase and Endothelial Lipase Have Different Substrate Specificities for High-Density Lipoprotein Phospholipids

Abstract

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