Hormone-sensitive lipase
Encyclopedia
Hormone-sensitive lipase (HSL) also previously known as cholesteryl ester hydrolase (CEH) is an enzyme
that, in humans, is encoded by the LIPE gene
.
HSL is an intracellular neutral lipase
that is capable of hydrolyzing a variety of ester
s. The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl ester
s to free cholesterol
for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglyceride
s to free fatty acid
s.
and diglyceride
. It is also known as triglyceride lipase, while the enzyme that cleaves the second fatty acid in the triglyceride is known as diglyceride lipase, and the third enzyme that cleaves the final fatty acid is called monoglyceride lipase. Only the initial enzyme is affected by hormones, hence its hormone-sensitive lipase name. The diglyceride and monoglyceride enzymes are tens to hundreds of times faster, hence HSL is the rate-limiting step in cleaving fatty acids from the triglyceride molecule.
HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH, and negatively to insulin
. Previously, glucagon was thought to activate HSL, however the removal of insulin's inhibitory effects ("cutting the brakes") is the source of activation. The lipolytic effect of glucagon in adipose tissue is minimal in humans.
Another important role is the release of cholesterol from cholesterol esters for use in the production of steroids.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that, in humans, is encoded by the LIPE gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
HSL is an intracellular neutral lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
that is capable of hydrolyzing a variety of ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s. The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl ester
Cholesteryl ester
A cholesteryl ester is, as its name would imply, an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Cholesteryl Esters have a lower solubility in water than Cholesterol and, in other words, are more hydrophobic...
s to free cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
s to free fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s.
Function
HSL functions to hydrolyze the first fatty acid from a triacylglycerol molecule, freeing a fatty acidFatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
and diglyceride
Diglyceride
A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....
. It is also known as triglyceride lipase, while the enzyme that cleaves the second fatty acid in the triglyceride is known as diglyceride lipase, and the third enzyme that cleaves the final fatty acid is called monoglyceride lipase. Only the initial enzyme is affected by hormones, hence its hormone-sensitive lipase name. The diglyceride and monoglyceride enzymes are tens to hundreds of times faster, hence HSL is the rate-limiting step in cleaving fatty acids from the triglyceride molecule.
HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH, and negatively to insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
. Previously, glucagon was thought to activate HSL, however the removal of insulin's inhibitory effects ("cutting the brakes") is the source of activation. The lipolytic effect of glucagon in adipose tissue is minimal in humans.
Another important role is the release of cholesterol from cholesterol esters for use in the production of steroids.
Activation
It may be activated by two mechanisms.- In the first, phosphorylated perilipinPerilipinPerilipin, also known as lipid droplet-associated protein or PLIN, is a protein that, in humans, is encoded by the PLIN gene.- Function :Perilipin is a protein that coats lipid droplets in adipocytes, the fat-storing cells in adipose tissue...
A causes it to move to the surface of the lipid droplet, where it may begin hydrolyzing the lipid droplet.
- Also, it may be activated by a cAMP-dependent protein kinaseCAMP-dependent protein kinaseIn cell biology, Protein kinase A refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP . PKA is also known as cAMP-dependent protein kinase...
(PKA). This pathway is significantly less effective than the first, which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs proteinGs alpha subunitThe Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...
-coupled receptors that promote cAMP production. Examples include beta adrenergic stimulation of the glucagon receptorGlucagon receptorThe glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...
and ACTH stimulation of the ACTH receptorACTH receptorThe ACTH receptor is a type of melanocortin receptor , properly known as MC2, which is specific for ACTH.It is found in the zona fasciculata of the human adrenal cortex. Binding of the receptor by ACTH stimulates the production of cortisol...
in the adrenal cortex.