In vitro lipolysis by human pancreatic lipase is specifically abolished by its inactive forms.
In human adults, the enzymatic hydrolysis of dietary fat along the digestive tract is sequentially catalyzed by two main enzymes, human gastric lipase (HGL) and human pancreatic lipase (HPL). Both a chemically inhibited form of HPL as well as an inactive HPL mutant with a glycine residue substituted for its catalytic serine were found to be strong inactivators of HPL activity. In the presence of bile salts, this inhibition was clearly due to competition for colipase. We established that the chemically inhibited HPL, probably in its open conformation, had a much greater affinity for colipase than the closed native form of HPL. These inhibitory effects are quite substantial, because a 0.2-M excess of the chemically inhibited HPL form relative to HPL reduced the catalytic lipolytic activity by 50% in the presence of an equimolar amount of colipase.
Miled
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N
Laboratoire de Lipolyse Enzymatique, IBSM, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseilles Cedex 20, France.
Berti-Dupuis
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L
Riviere
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M
Carrière
F
F
Verger
R
R
D000873:Anthracenes; D001647:Bile Acids and Salts; D003089:Colipases / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004793:Enzyme Reactivators / Q000494:pharmacology; D005456:Fluorescent Dyes; D005998:Glycine / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008066:Lipolysis; D009154:Mutation; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology*; D010189:Pancreatic Juice / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000235:genetics
D000873:Anthracenes; D001647:Bile Acids and Salts; D003089:Colipases; D004791:Enzyme Inhibitors; D004793:Enzyme Reactivators; D005456:Fluorescent Dyes; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D012694:Serine; C049062:1-aminoanthracene; D008049:Lipase; C075987:pancreatic lipase-related protein 1; D005998:Glycine