Biochemistry, Lipase

Article Author:
Yasaman Pirahanchi
Article Editor:
Sandeep Sharma
Updated:
2/2/2019 2:33:36 PM
PubMed Link:
Biochemistry, Lipase

Introduction

Lipase is an enzyme that breaks down triglycerides into free fatty acids and glycerol. Lipases are present in pancreatic secretions and are responsible for fat digestion. There are many different types of lipases; for example, hepatic lipases are in the liver, hormone-sensitive lipases are in adipocytes, lipoprotein lipase is in the vascular endothelial surface, and pancreatic lipase in the small intestine. Understanding lipase is crucial for understanding the pathophysiology of fat necrosis and is clinically significant in the understanding of acute and chronic pancreatitis. The role of lipase is also crucial in the mechanism of some medications indicated for lowering cholesterol. This review will explore the function, pathophysiology, and clinical significance of the lipase enzyme.[1]

Molecular

The lipase group of enzymes is built on alpha and beta hydrolase folds. They work by employing chymotrypsin-like hydrolysis, which uses a histidine base, a serine nucleophile, and aspartic acid.

Function

Lipase is an enzyme that breaks down triglycerides into free fatty acids and glycerol. Lipases are present in pancreatic secretions and are responsible for fat digestion. Lipases are enzymes that play a crucial role in lipid transport. There are many different types of lipases; hepatic lipases are in the liver, hormone-sensitive lipases are in adipocytes, lipoprotein lipase is in the vascular endothelial surface, and pancreatic lipase is in the small intestine, each serving individual functions. Hepatic lipase in the liver is responsible for degrading the triglycerides that remain in intermediate density lipoprotein (IDL). Hormone-sensitive lipase is found within fat tissue and is responsible for degrading the triglycerides that are stored within adipocytes. Lipoprotein lipase is found on the vascular endothelial surface and is responsible for degrading triglycerides that circulating from chylomicrons and VLDLs. Pancreatic lipase is found within the small intestine and is responsible for degrading dietary triglycerides. [2]

Hepatic lipase plays a crucial role in the formation and delivery of low-density lipoprotein(LDL). LDL is formed by the modification of intermediate density lipoprotein in the peripheral tissue and liver by hepatic lipase. These LDL particles are taken up, or endocytosed, via receptor-mediated endocytosis by target cell tissue. LDL serves to ultimately transport cholesterol from the liver to peripheral tissue.[3]

Pathophysiology

Fat necrosis occurs enzymatically and non-enzymatically. In acute pancreatitis, saponification of peripancreatic fat occurs. During traumatic events, such as physical injury in breast tissue, non-enzymatic fat necrosis takes place. This is due to the damage to fat cells causing the release of lipase, leading to triglyceride breakdown, and causing the release of fatty acids. These fatty acids are charged negatively and once released in the bloodstream, bind to positively charged calcium ions. This process of salt formation between negatively charged fatty acids and positively charged calcium ions is called saponification.[4]

Histologically, saponified cells appear as dead fat cells outlining the tissue, which do not contain peripheral nuclei. Saponification of the fatty acid and calcium ion combined on hematoxylin and eosin staining appears dark blue. [5]

Clinical Significance

High levels of serum lipase may be indicative of pancreatitis. In the case of acute pancreatitis, diagnosis is based on results with two of the three criteria. The criteria used for diagnosis include acute epigastric pain radiating to the back, increased serum amylase, or increased lipase levels which are up to three times the upper limit of normal serum lipase levels. The latter is a more specific diagnostic marker than amylase or imaging with CT or MRI. Acute pancreatitis is due to autodigestion of pancreas by pancreatic enzymes, causing surrounding edema around the pancreas. Causes of this pathology include excessive ethanol use, gallstones, trauma, mumps, steroids, autoimmune disease, hypertriglyceridemia with levels above 1000 mg/dL, hypercalcemia, ERCP, Scorpion sting, or drugs such as nucleoside reverse transcriptase inhibitors, protease inhibitors, or sulfa drugs. Acute pancreatitis can lead to complications including pseudocyst, in which the pancreatic lining is composed of granulation tissue rather than epithelium, necrosis, abscess, infection, hemorrhage, hypocalcemia precipitation of calcium soaps, or organ failure including acute respiratory distress syndrome, shock, or renal failure.[6]

Elevated serum levels of lipase and amylase may or may not also be present in chronic pancreatitis, in contrast to acute pancreatitis where serum lipase is almost always elevated. Chronic pancreatitis is due to chronic inflammation, calcification, and atrophy of the pancreas. The primary causes of this pathology include chronic alcohol abuse in adults and genetic predisposition such as cystic fibrosis in children. It can also be due to idiopathic causes. Complications of chronic pancreatitis include deficiency of pancreatic enzymes and pseudocysts. Pancreatic insufficiency usually occurs when there is less than ten percent of pancreatic function remaining, due to a deficiency in pancreatic enzymes contained within the pancreas to digest fats such as lipase. This pancreatic enzyme deficiency leads to clinical manifestations of steatorrhea, as fat is not absorbed properly in the small intestine and it is instead excreted. Because of this inability to absorb fats properly, this can also clinically manifest as fat-soluble vitamin deficiency of vitamins A, D, E, and K. Pancreatic insufficiency can also lead to diabetes mellitus, due to lack of sufficient insulin release from pancreatic tissue. [7]   

Clinically, orlistat is a medication used for weight loss that acts on lipase. Specifically, this medication inhibits pancreatic and gastric lipases. This inhibition of lipase leads to reduced breakdown and absorption of dietary fats. This can lead to side effects as a consequence of decreased absorption of fats, such as decreased absorption of fat-soluble vitamins A, D, E, and K. Side effects also include abdominal pain, frequent bowel movements or bowel urgency, and flatulence.[8]

Some cholesterol-lowering medications act on lipases. Fibrates, such as bezafibrate, gemfibrozil, and fenofibrate, work by activating Peroxisome proliferator-activated receptor alpha(PPAR-alpha), and upregulating lipoprotein lipase, which leads to a decrease in serum triglyceride levels along with induction of increased synthesis of HDL. Fibrates are clinically indicated primarily for lowering triglycerides. Side effects of fibrates include cholesterol gallstones, rhabdomyolysis, especially if used with statins, and increased LDL.[9]

Niacin, or vitamin B3, is another cholesterol-lowering medication that acts on lipase. Specifically, lipase acts to inhibit hormone-sensitive lipase, which leads to inhibition of VLDL synthesis in the liver. Niacin is clinically indicated primarily for increasing HDL levels. Side effects erythema and flushing of the upper body, increased glucose levels, increased uric acid levels, acanthosis nigricans, and pruritus.[10]


References

[1] Cerk IK,Wechselberger L,Oberer M, Adipose Triglyceride Lipase Regulation: An Overview. Current protein     [PubMed PMID: 28925902]
[2] Waldmann E,Parhofer KG, Apheresis for severe hypercholesterolaemia and elevated lipoprotein(a). Pathology. 2019 Jan 2;     [PubMed PMID: 30611543]
[3] Lotta LA,Stewart ID,Sharp SJ,Day FR,Burgess S,Luan J,Bowker N,Cai L,Li C,Wittemans LBL,Kerrison ND,Khaw KT,McCarthy MI,O'Rahilly S,Scott RA,Savage DB,Perry JRB,Langenberg C,Wareham NJ, Association of Genetically Enhanced Lipoprotein Lipase-Mediated Lipolysis and Low-Density Lipoprotein Cholesterol-Lowering Alleles With Risk of Coronary Disease and Type 2 Diabetes. JAMA cardiology. 2018 Oct 1;     [PubMed PMID: 30326043]
[4] Aloysius TA,Carvajal AK,Slizyte R,Skorve J,Berge RK,Bjørndal B, Chicken Protein Hydrolysates Have Anti-Inflammatory Effects on High-Fat Diet Induced Obesity in Mice. Medicines (Basel, Switzerland). 2018 Dec 28;     [PubMed PMID: 30597839]
[5] Prieto Vidal N,Adeseun Adigun O,Pham TH,Mumtaz A,Manful C,Callahan G,Stewart P,Keough D,Thomas RH, The Effects of Cold Saponification on the Unsaponified Fatty Acid Composition and Sensory Perception of Commercial Natural Herbal Soaps. Molecules (Basel, Switzerland). 2018 Sep 14;     [PubMed PMID: 30223479]
[6] Ismail OZ,Bhayana V, Lipase or amylase for the diagnosis of acute pancreatitis? Clinical biochemistry. 2017 Dec;     [PubMed PMID: 28720341]
[7] Oh HC,Kwon CI,El Hajj II,Easler JJ,Watkins J,Fogel EL,McHenry L,Sherman S,Zimmerman MK,Lehman GA, Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis. Gut and liver. 2017 Nov 15;     [PubMed PMID: 29081212]
[8] Pamuk B,Yilmaz H,Kebapçilar L,Kirbiyik H,Alacacio─člu A,Bozkaya G,Pamuk G,Demirpence M, The effect of orlistat and weight loss diet on plasma ghrelin and obestatin. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2018;     [PubMed PMID: 30595703]
[9] Inácio MD,Rafacho A,de Paula Camaforte NA,Teixeira P,Vareda PMP,Violato NM,Bosqueiro JR, Prevention of Elevation in Plasma Triacylglycerol with High-Dose Bezafibrate Treatment Abolishes Insulin Resistance and Attenuates Glucose Intolerance Induced by Short-Term Treatment with Dexamethasone in Rats. International journal of endocrinology. 2018;     [PubMed PMID: 30532777]
[10] Gupta KK,Ali S,Sanghera RS, Pharmacological Options in Atherosclerosis: A Review of the Existing Evidence. Cardiology and therapy. 2018 Dec 12;     [PubMed PMID: 30543029]