The dynamic metabolism of hyaluronan regulates the cytosolic concentration of UDP-GlcNAc.
Hyaluronan, a macromolecular glycosaminoglycan, is normally synthesized by hyaluronan synthases at the plasma membrane using cytosolic UDP-GlcUA and UDP-GlcNAc substrates and extruding the elongating chain into the extracellular space. The cellular metabolism (synthesis and catabolism) of hyaluronan is dynamic. UDP-GlcNAc is also the substrate for O-GlcNAc transferase, which is central to the control of many cytosolic pathways. This Perspective outlines recent data for regulation of hyaluronan synthesis and catabolism that support a model that hyaluronan metabolism can be a rheostat for controlling an acceptable normal range of cytosolic UDP-GlcNAc concentrations in order to maintain normal cell functions.
Biomedical Engineering, Cleveland Clinic, OH 44195, United States. Electronic address: hascalv@ccf.org.
Vincent C
VC
Hascall
Biomedical Engineering, Cleveland Clinic, OH 44195, United States.
Aimin
A
Wang
School of Medicine, Institute of Biomedicine/Anatomy, University of Eastern Finland, 70211 Kuopio, Finland.
Markku
M
Tammi
School of Medicine, Institute of Biomedicine/Anatomy, University of Eastern Finland, 70211 Kuopio, Finland.
Sanna
S
Oikari
School of Medicine, Institute of Biomedicine/Anatomy, University of Eastern Finland, 70211 Kuopio, Finland.
Raija
R
Tammi
Dipartimento di Scienze e Morfologiche, Universita degli Studi dell'Insubria, 21100 Varese, Italy.
Alberto
A
Passi
Dipartimento di Scienze e Morfologiche, Universita degli Studi dell'Insubria, 21100 Varese, Italy.
Davide
D
Vigetti
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, United States.
Richard W
RW
Hanson
Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD 21205-2185, United States.
Gerald W
GW
Hart
D000818:Animals; D002468:Cell Physiological Phenomena / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000378:metabolism*; D008954:Models, Biological; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism*
D014537:Uridine Diphosphate N-Acetylglucosamine; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases
Hyaluronan; Hyaluronan synthases; O-GlcNAc transferase; UDP-GlcNAc