Bile salt-activated lipase

 

Bile salt-activated lipase (BAL) is one of two lipases secreted from the vertebrate pancreas into the intestine for the digestion of fat. It also catalyses vitamin absorption. It acts in concert with pancreatic lipase and colipase for the complete digestion of dietary triglycerides.

In a few mammals, BAL is also present in the milk to facilitate fat absorption in infants. Because of its wide range of substrate reactivities, BAL has been documented with several different names, including pancreatic carboxylester lipase, pancreatic cholesterol esterase, triacylglycerol lipase and lysophospholipase. There is evidence to support the importance of BAL for the absorption of cholesterol, vitamin A and triacylglycerol. The hydrolytic activity of BAL on naturally occurring lipids requires the presence of bile salt.

 

Reference Protein and Structure

Sequence
P30122 UniProt (3.1.1.3, 3.1.1.6, 3.1.1.13) IPR033560 (Sequence Homologues) (PDB Homologues)
Biological species
Bos taurus (Cattle) Uniprot
PDB
1aql - CRYSTAL STRUCTURE OF BOVINE BILE-SALT ACTIVATED LIPASE COMPLEXED WITH TAUROCHOLATE (2.8 Å) PDBe PDBsum 1aql
Catalytic CATH Domains
3.40.50.1820 CATHdb (see all for 1aql)
Click To Show Structure

Enzyme Reaction (EC:3.1.1.13)

cholesteryl ester
CHEBI:17002ChEBI
+
water
CHEBI:15377ChEBI
→
cholesterol
CHEBI:16113ChEBI
+
fatty acid anion
CHEBI:28868ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: Acylcholesterol lipase, Cholesterase, Cholesterol ester hydrolase, Cholesterol esterase, Cholesteryl ester hydrolase, Cholesteryl ester synthase, Cholesteryl esterase, Sterol ester hydrolase, Triterpenol esterase, Cholesterol ester synthase,

Enzyme Mechanism

Introduction

BAL utilises a Ser/His/Asp catalytic triad to hydrolyse an ester bond by nucleophilic substitution. The reaction has two stages: in the first, an enzyme-substrate bond is formed and in the second it is hydrolysed by water.

Catalytic Residues Roles

UniProt PDB* (1aql)
His453 His435A Deprotonates serine to activate it as a nucleophile. proton shuttle (general acid/base)
Ser212 Ser194A Carries out a nucleophilic attack on the substrate. covalent catalysis
Asp338 Asp320A Stabilises charges on His435, activating it as a general acid/base. activator, electrostatic stabiliser
Ala126 (main-N), Ala213 (main-N), Gly125 (main-N) Ala108A (main-N), Ala195A (main-N), Gly107A (main-N) Forms part of the oxyanion hole to stabilise the negatively charged transition state. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Wang X et al. (1997), Structure, 5, 1209-1218. The crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism. DOI:10.1016/s0969-2126(97)00271-2. PMID:9331420.
  2. Saele Ø et al. (2010), Comp Biochem Physiol A Mol Integr Physiol, 157, 252-259. Characterization and expression of digestive neutral lipases during ontogeny of Atlantic cod (Gadus morhua). DOI:10.1016/j.cbpa.2010.07.003. PMID:20624477.
  3. Aubert-Jousset E et al. (2004), J Biol Chem, 279, 39697-39704. Site-directed Mutagenesis of the Distal Basic Cluster of Pancreatic Bile Salt-dependent Lipase. DOI:10.1074/jbc.m407646200. PMID:15265857.

Step 1.

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Catalytic Residues Roles

Residue Roles
Ser194A covalent catalysis
His435A proton shuttle (general acid/base)
Asp320A electrostatic stabiliser, activator
Gly107A (main-N) electrostatic stabiliser
Ala108A (main-N) electrostatic stabiliser
Ala195A (main-N) electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Stuart Lucas, Craig Porter, Gemma L. Holliday