Human gastric lipase

Bernbäck, Stefan; Bläckberg, Lars

doi:10.1111/j.1432-1033.1989.tb14855.x

Cited by 19 publications

(3 citation statements)

References 22 publications

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“…This suggests that, despite proteolysis, capacity to hydrolyse substrates is retained in smaller fragments, whereas recognition and hydrolysis of the phospholipid emulsified lipid substrates depends on a more intact HSL molecule. Analyses of both lipoprotein lipase (LPL) [43] and gastric lipase (GL) [44] during proteolysis, have similarly shown that lipase activity is affected more than esterase activity during proteolysis. The fact that TO activity declines more rapidly than CO and MOME activities, can be explained by differences in substrate accessibility at the interface of the different lipid emulsions.…”

Section: Limited Proteolysis and Denaturationmentioning

confidence: 99%

Domain-structure analysis of recombinant rat hormone-sensitive lipase

Østerlund

Danielsson

Degerman

et al. 1996

Biochemical Journal

144

166

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Hormone-sensitive lipase (HSL) plays a key role in lipid metabolism and overall energy homoeostasis, by controlling the release of fatty acids from stored triglycerides in adipose tissue. Lipases and esterases form a protein superfamily with a common structural fold, called the alpha/beta-hydrolase fold, and a catalytic triad of serine, aspartic or glutamic acid and histidine. Previous alignments between HSL and lipase 2 of Moraxella TA144 have been extended to cover a much larger part of the HSL sequence. From these extended alignments, possible sites for the catalytic triad and alpha/beta-hydrolase fold are suggested. Furthermore, it is proposed that HSL contains a structural domain with catalytic capacity and a regulatory module attached, as well as a structural N-terminal domain unique to this enzyme. In order to test the proposed domain structure, rat HSL was overexpressed and purified to homogeneity using a baculovirus/insect-cell expression system. The purification, resulting in > 99% purity, involved detergent solubilization followed by anion-exchange chromatography and hydrophobic-interaction chromatography. The purified recombinant enzyme was identical to rat adipose-tissue HSL with regard to specific activity, substrate specificity and ability to serve as a substrate for cAMP-dependent protein kinase. The recombinant HSL was subjected to denaturation by guanidine hydrochloride and limited proteolysis. These treatments resulted in more extensive loss of activity against phospholipid-stabilized lipid substrates than against water-soluble substrates, suggesting that the hydrolytic activity can be separated from recognition of lipid substrates. These data support the concept that HSL has at least two major domains.

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Section: Limited Proteolysis and Denaturationmentioning

confidence: 99%

Domain-structure analysis of recombinant rat hormone-sensitive lipase

Østerlund

Danielsson

Degerman

et al. 1996

Biochemical Journal

144

166

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“…The binding mechanism of gastric lipase to emulsified TAG is not completely elucidated, but involves conformational changes in a lid domain that controls access to the active site upon lid opening (40,41). The N-terminal tetrapeptide has also been shown to be important for binding to long chain TAG emulsions (42). This probably involves the N-terminal hydrophobic residues (Leu-Phe) that are part of the interfacial recognition site, and also the presence of a charged residue (Lys4), that is involved in the stabilisation of the lid domain via a salt bridge with Glu225 present in the lid (41).…”

Section: Human Gastric Lipasementioning

confidence: 99%

Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption

2018

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Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to 'pre-process' lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

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“…A dog recombinant lipase, rGL, was produced to test this concept153 and was developed by the French company Meristem Therapeutics SA, Clermont-Ferrand (Merispase), that went out of business in September 2008. This approach is problematic for several reasons: gastric lipase specific activity is about 10 times lower than that of pancreatic lipase (measured on tributyrin);51 it is highly sensitive to trypsin proteolysis;154 and endogenous secretion of gastric lipase can be increased in patients with pancreatic insufficiency28 because of possible nutritional adaptation 98,155. However, gastric lipase supplements may still be a viable option.…”

Section: Future Developments For An Optimal Therapymentioning

confidence: 99%

Enzyme replacement therapy for pancreatic insufficiency: present and future

Fieker¹,

Philpott²,

Armand³

2011

CEG

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Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.

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Human gastric lipase

Cited by 19 publications

References 22 publications

Domain-structure analysis of recombinant rat hormone-sensitive lipase

Domain-structure analysis of recombinant rat hormone-sensitive lipase

Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption

Enzyme replacement therapy for pancreatic insufficiency: present and future

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