title: Ceramidases, roles in sphingolipid metabolism and in health and disease.
abstract: Over the past three decades, extensive research has been able to determine the biologic functions for the main bioactive sphingolipids, namely ceramide, sphingosine, and sphingosine 1-phosphate (S1P) (Hannun, 1996; Hannun et al., 1986; Okazaki et al., 1989). These studies have managed to define the metabolism, regulation, and function of these bioactive sphingolipids. This emerging body of literature has also implicated bioactive sphingolipids, particularly S1P and ceramide, as key regulators of cellular homeostasis. Ceramidases have the important role of cleaving fatty acid from ceramide and producing sphingosine, thereby controlling the interconversion of these two lipids. Thus far, five human ceramidases encoded by five different genes have been identified: acid ceramidase (AC), neutral ceramidase (NC), alkaline ceramidase 1 (ACER1), alkaline ceramidase 2 (ACER2), and alkaline ceramidase 3 (ACER3). These ceramidases are classified according to their optimal pH for catalytic activity. AC, which is localized to the lysosomal compartment, has been associated with Farber's disease and is involved in the regulation of cell viability. Neutral ceramidase, which is localized to the plasma membrane and primarily expressed in the small intestine and colon, is involved in digestion, and has been implicated in colon carcinogenesis. ACER1 which can be found in the endoplasmic reticulum and is highly expressed in the skin, plays an important role in keratinocyte differentiation. ACER2, localized to the Golgi complex and highly expressed in the placenta, is involved in programed cell death in response to DNA damage. ACER3, also localized to the endoplasmic reticulum and the Golgi complex, is ubiquitously expressed, and is involved in motor coordination-associated Purkinje cell degeneration. This review seeks to consolidate the current knowledge regarding these key cellular players.
authors: Health Science Center, Stony Brook University, 100 Nicolls Road, T15, 023, 11794, Stony Brook, NY, USA. Electronic address: Nicolas.Coant@stonybrookmedicine.edu.
authors: Nicolas
authors: N
authors: Coant
authors: Health Science Center, Stony Brook University, 100 Nicolls Road, T15, 023, 11794, Stony Brook, NY, USA. Electronic address: Wataru.Sakamoto@stonybrookmedicine.edu.
authors: Wataru
authors: W
authors: Sakamoto
authors: Health Science Center, Stony Brook University, 100 Nicolls Road, T15, 023, 11794, Stony Brook, NY, USA. Electronic address: Cungui.Mao@stonybrookmedicine.edu.
authors: Cungui
authors: C
authors: Mao
authors: Health Science Center, Stony Brook University, 100 Nicolls Road, L4, 182, 11794, Stony Brook, NY, USA. Electronic address: Yusuf.Hannun@stonybrookmedicine.edu.
authors: Yusuf A
authors: YA
authors: Hannun
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics / Q000378:metabolism*; D055574:Alkaline Ceramidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055577:Farber Lipogranulomatosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D007700:Kinetics; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D055576:Neutral Ceramidase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D013107:Sphingolipids; C526750:ACER1 protein, human; C526755:ACER2 protein, human; C000619511:ACER3 protein, human; D055573:Acid Ceramidase; D055574:Alkaline Ceramidase; D055576:Neutral Ceramidase
keywords: Cancer; Cell proliferation; Ceramidase; Farber's disease; Sphingolipid; Sphingosine