Effect of colipase on adsorption and activity of rat pancreatic lipase on emulsified tributyrin in the presence of bile salt

Vandermeers, André; Vandermeers‐Piret, Marie‐Claire; Rathé, Jean; Christophe, Jean

doi:10.1016/0014-5793(75)80779-4

Cited by 66 publications

(29 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bile salts desorb lipase from such interfaces thus affecting an inhibition of the enzyme due to physical separation from the substrate [ 1,3] . The inhibition is reversed by colipase [4] -a polypeptide cofactor -which makes possible the binding of lipase to the substrate interface in the presence of bile salts [1, 3,5]. The complete system; lipase/colipase/biIe salt/substrate, has an important physiological role and displays several interesting physico-chemical interactions of protein-protein and protein-detergent nature.…”

Section: Introductionmentioning

confidence: 99%

“…The complete system; lipase/colipase/biIe salt/substrate, has an important physiological role and displays several interesting physico-chemical interactions of protein-protein and protein-detergent nature. Colipase has previously been found to bind to the lipasesubstrate interface [ 1,3] even in the presence of bile salts guiding the enzyme to its active site. The present results, however, indicate that detkrgents will displace also colipase from interfaces and that a certain specificity is obviously related to the structure of the detergent and the quality of the interface.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Binding of pancreatic colipase to interfaces; effects of detergents

Borgström¹

1976

FEBS Letters

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Binding of pancreatic colipase to interfaces; effects of detergents

Borgström¹

1976

FEBS Letters

View full text Add to dashboard Cite

“…Lipase adsorption is a fundamental process because the enzyme catalyzes a heterogeneous reaction that involves an interfacial activation step. To counteract the inhibitory effect of bile salts, the pancreas secretes a small protein, colipase (molecular mass, 10 kDa), which anchors lipase to the bile salt-coated water-lipid interface in their presence (2,3). Thus, lipolysis results from the combined effect of pancreatic lipase, colipase, and bile salts.…”

mentioning

confidence: 99%

“…3). 3 Although such bridging contact should be conserved in the human natural complex, it has been broken in the human-porcine complex presumably because of the more favorable double interaction of Asp 390 with Arg 44 (Fig. 3) .…”

mentioning

confidence: 99%

Lipase Activation by Nonionic Detergents

Hermoso

Pignol

Kerfélec

et al. 1996

Journal of Biological Chemistry

210

View full text Add to dashboard Cite

The crystal structure of the ternary porcine lipasecolipase-tetra ethylene glycol monooctyl ether (TGME) complex has been determined at 2.8 Å resolution. The crystals belong to the cubic space group F23 with a ‫؍‬ 289.1 Å and display a strong pseudo-symmetry corresponding to a P23 lattice. Unexpectedly, the crystalline two-domain lipase is found in its open configuration. This indicates that in the presence of colipase, pure micelles of the nonionic detergent TGME are able to activate the enzyme; a process that includes the movement of an N-terminal domain loop (the flap). The effects of TGME and colipase have been confirmed by chemical modification of the active site serine residue using diisopropyl p-nitrophenylphosphate (E600). In addition, the presence of a TGME molecule tightly bound to the active site pocket shows that TGME acts as a substrate analog, thus possibly explaining the inhibitory effect of this nonionic detergent on emulsified substrate hydrolysis at submicellar concentrations. A comparison of the lipase-colipase interactions between our porcine complex and the human-porcine complex (van Tilbeurgh, H., Egloff, M.-P., Martinez, C., Rugani, N., Verger, R., and Cambillau, C. (1993) Nature 362, 814 -820) indicates that except for one salt bridge interaction, they are conserved. Analysis of the superimposed complexes shows a 5.4°rotation on the relative position of the N-terminal domains excepting the flap that moves in a concerted fashion with the C-terminal domain. This flexibility may be important for the binding of the complex to the water-lipid interface.Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) plays a key role in dietary fat absorption in the intestine. It converts insoluble long chain triglycerides into more polar molecules that are able to cross the brush border membrane of enterocytes as mixed micelles with bile salts. Besides their role in triglyceride digestion through lipid emulsification and intestinal fat absorption, bile salts exert a strong inhibitory effect by preventing lipase adsorption through coating of the water-lipid interface (1). Lipase adsorption is a fundamental process because the enzyme catalyzes a heterogeneous reaction that involves an interfacial activation step. To counteract the inhibitory effect of bile salts, the pancreas secretes a small protein, colipase (molecular mass, 10 kDa), which anchors lipase to the bile salt-coated water-lipid interface in their presence (2, 3). Thus, lipolysis results from the combined effect of pancreatic lipase, colipase, and bile salts.Pancreatic lipase is a single polypeptide chain of 50 kDa. This protein has been characterized in several species, and the amino acid sequences of the enzyme from pig, man, horse, rabbit, rat, guinea pig, and coypu (4 -10) have been reported. In addition, related lipases (type 1 and 2) have been found in dog, rat man, guinea pig, and coypu (11-16) by screening pancreatic cDNA libraries. The localization and role of these related lipases is not clear.Crystal structures of the human ...

show abstract

“…By calorimetric studies it was shown that pancreatic lipase and colipase form a 1 : 1 complex [2]. The inhibitory effect of bile salt was explained as a physical displacement of lipase from the substrate interface [3] and the reactivating effect of colipase was due to its adsorption to the triglyceride/water interface which occurs in spite of the presence of bile salt thereby enabling the coadsorption of lipase [3,4]. This idea of colipase acting by first penetrating the lipid film and then serving as an anchor for lipase into the film was recently confirmed using the monolayer technique for preparation of the substrate [5].…”

Section: Introductionmentioning

confidence: 99%

Chemical modification of pancreatic lipase Effect on the colipase‐reactivated and the ‘true’ lipase activity

Erlanson¹

1977

FEBS Letters

View full text Add to dashboard Cite

Effect of colipase on adsorption and activity of rat pancreatic lipase on emulsified tributyrin in the presence of bile salt

Cited by 66 publications

References 8 publications

Binding of pancreatic colipase to interfaces; effects of detergents

Binding of pancreatic colipase to interfaces; effects of detergents

Lipase Activation by Nonionic Detergents

Chemical modification of pancreatic lipase Effect on the colipase‐reactivated and the ‘true’ lipase activity

Contact Info

Product

Resources

About