PNPLA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | PNPLA2, 1110001C14Rik, ATGL, PEDF-R, TTS-2.2, TTS2, iPLA2zeta, FP17548, patatin like phospholipase domain containing 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 609059; MGI: 1914103; HomoloGene: 10687; GeneCards: PNPLA2; OMA: PNPLA2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene. [5] [6] [7] ATGL catalyses the first reaction of lipolysis, [8] where triacylglycerols are hydrolysed to diacylglycerols. [9]
ATGL has very high substrate specificity for triacylglycerols. [10] It contains a catalytic dyad using serine- aspartic acid. [9]
ATGL catalyses the first reaction of lipolysis. [8] It hydrolysis triacylglycerols to diacylglycerols [9] by attacking the fatty acid attached to carbon-3 of glycerol.
ATGL acts as a control mechanism of lipolysis, as variations in diacylglycerol concentration impact enzymes in later stages of lipolysis. [11]
Defects in ATGL can cause problems in lipolysis, leading to neutral lipid storage disease. [12] As triacylglycerols are not hydrolysed to diacylglycerols, there is a build-up of triacylglycerol droplets in granulocytes. [12]
ATGL is regulated by insulin, and is similar to structure with adiponutrin, a protein that is regulated by nutrition. When there is a lack of insulin, there is an increased expression of the ATGL protein. Because adipose tissue triglyceride is a major form of energy storage, the study of how ATGL regulation and dysregulation can lead to potential problems will increase understanding of the pathophysiology behind metabolic disorders. [13] ATGL is also the key enzyme that would be able to maintain a balance between mobilization and lipid storage. Lipolytic breakdown performed by ATGL would impact regulatory functions including but not limited to cell death, growth, signaling, metabolism, and gene expression. [14] [15]
There must be mechanisms set to maintain the balance between energy storage, and energy release; a dysregulation in the equilibrium result in metabolic disorder, a prime one being diabetes. [13] Adipose Triglyceride Lipase (ATGL) can undergo activation through two different pathways: transcriptionally and through post-translational modification. Through the transcriptional pathway, Beta-adrenergic, a receptor that can form a complex with agonist such as epinephrine, results in the signal transduction pathway activation of Adipose Triglyceride Lipase (ATGL). The alternative pathway is through a post-translational modification specifically phosphorylation of a serine 406 residue located on the enzyme by a kinase known as AMP activated protein kinase (AMPK). Both pathways facilitate the activation of the enzyme, resulting in the breakdown of triglyceride. [16]
Insulin is a hormone that regulate the enzyme ATGL, it inhibits the enzyme by favoring lipid storage over lipolysis. [13] One pathway of inhibition of ATGL when insulin is present is the activation of SIRT1, which inhibits FoxO1. [16] [17] Specifically, FoxO1 is repressed from localizing in the nucleus by deacetylation in adipocytes. [16] [18]
PNPLA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | PNPLA2, 1110001C14Rik, ATGL, PEDF-R, TTS-2.2, TTS2, iPLA2zeta, FP17548, patatin like phospholipase domain containing 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 609059; MGI: 1914103; HomoloGene: 10687; GeneCards: PNPLA2; OMA: PNPLA2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene. [5] [6] [7] ATGL catalyses the first reaction of lipolysis, [8] where triacylglycerols are hydrolysed to diacylglycerols. [9]
ATGL has very high substrate specificity for triacylglycerols. [10] It contains a catalytic dyad using serine- aspartic acid. [9]
ATGL catalyses the first reaction of lipolysis. [8] It hydrolysis triacylglycerols to diacylglycerols [9] by attacking the fatty acid attached to carbon-3 of glycerol.
ATGL acts as a control mechanism of lipolysis, as variations in diacylglycerol concentration impact enzymes in later stages of lipolysis. [11]
Defects in ATGL can cause problems in lipolysis, leading to neutral lipid storage disease. [12] As triacylglycerols are not hydrolysed to diacylglycerols, there is a build-up of triacylglycerol droplets in granulocytes. [12]
ATGL is regulated by insulin, and is similar to structure with adiponutrin, a protein that is regulated by nutrition. When there is a lack of insulin, there is an increased expression of the ATGL protein. Because adipose tissue triglyceride is a major form of energy storage, the study of how ATGL regulation and dysregulation can lead to potential problems will increase understanding of the pathophysiology behind metabolic disorders. [13] ATGL is also the key enzyme that would be able to maintain a balance between mobilization and lipid storage. Lipolytic breakdown performed by ATGL would impact regulatory functions including but not limited to cell death, growth, signaling, metabolism, and gene expression. [14] [15]
There must be mechanisms set to maintain the balance between energy storage, and energy release; a dysregulation in the equilibrium result in metabolic disorder, a prime one being diabetes. [13] Adipose Triglyceride Lipase (ATGL) can undergo activation through two different pathways: transcriptionally and through post-translational modification. Through the transcriptional pathway, Beta-adrenergic, a receptor that can form a complex with agonist such as epinephrine, results in the signal transduction pathway activation of Adipose Triglyceride Lipase (ATGL). The alternative pathway is through a post-translational modification specifically phosphorylation of a serine 406 residue located on the enzyme by a kinase known as AMP activated protein kinase (AMPK). Both pathways facilitate the activation of the enzyme, resulting in the breakdown of triglyceride. [16]
Insulin is a hormone that regulate the enzyme ATGL, it inhibits the enzyme by favoring lipid storage over lipolysis. [13] One pathway of inhibition of ATGL when insulin is present is the activation of SIRT1, which inhibits FoxO1. [16] [17] Specifically, FoxO1 is repressed from localizing in the nucleus by deacetylation in adipocytes. [16] [18]