Introduction

History

Lipoprotein Lipase (LPL) enzyme was identified more than 60 years ago. Dr. Edward Korn isolated and named LPL in 1950 when he was able to extract the enzyme from a rat heart. Despite biochemists and physiologists intensely studying this enzyme, it wasn’t until recently that LPL’s detailed structure was determined due to LPL’s hydrolase domain susceptibility to unfolding. LMF1 and GPIHBP1 were discovered to be required for proper folding and enzymatic activity of LPL. LMF1 is a chaperone protein that is responsible for proper folding and secretion of LPL. Through the use of X-ray Crystallography it was also discovered that LPL is a monomer rather than the previously believed homodimer.

Function

LPL is located within the interstitial space independently and remains stranded there if not acted upon by GPIHBP1. GPIHBP1 then captures LPL in the interstitial spaces and shuttles it across endothelial cells into the capillary lumen. Once in the capillaries, the LPL-GPIHBP1 complex catalyzes the breakdown of triglycerides in the blood. In doing so, it prevents high levels of triglycerides in the plasma to provide nutrients for vital tissues.

Significance

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Structure

Overall Structure

LPL

N-terminus of LPL

Calcium Ion Coordination

Active Site

Mechanism

C-terminus of LPL

GPIHBP1

Disease

Mutations

D201V

M404R

Relevance

Hypertriglycerademia

Drug Relevance