Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease.

Autor: Aspatwar A; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Fimlab Ltd and Tampere University Hospital, Tampere, Finland., Supuran CT; Neurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Sesto Fiorentino, Firenze, Italy., Waheed A; Department of Biochemistry and Molecular Biology, Edward A. Doisy Research Center, Saint Louis University School of Medicine, St Louis, MO, USA., Sly WS; Department of Biochemistry and Molecular Biology, Edward A. Doisy Research Center, Saint Louis University School of Medicine, St Louis, MO, USA., Parkkila S; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Fimlab Ltd and Tampere University Hospital, Tampere, Finland.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2023 Jan; Vol. 601 (2), pp. 257-274. Date of Electronic Publication: 2022 Dec 19.
DOI: 10.1113/JP283579
Abstrakt: Carbonic anhydrase V (CA V), a mitochondrial enzyme, was first isolated from guinea-pig liver and subsequently identified in mice and humans. Later, studies revealed that the mouse genome contains two mitochondrial CA sequences, named Car5A and Car5B. The CA VA enzyme is most highly expressed in the liver, whereas CA VB shows a broad tissue distribution. Car5A knockout mice demonstrated a predominant role for CA VA in ammonia detoxification, whereas the roles of CA VB in ureagenesis and gluconeogenesis were evident only in the absence of CA VA. Previous studies have suggested that CA VA is mainly involved in the provision of HCO 3 - for biosynthetic processes. In children, mutations in the CA5A gene led to reduced CA activity, and the enzyme was sensitive to increased temperature. The metabolic profiles of these children showed a reduced supply of HCO 3 - to the enzymes that take part in intermediary metabolism: carbamoylphosphate synthetase, pyruvate carboxylase, propionyl-CoA carboxylase and 3-methylcrotonyl-CoA carboxylase. Although the role of CA VB is still poorly understood, a recent study reported that it plays an essential role in human Sertoli cells, which sustain spermatogenesis. Metabolic disease associated with CA VA appears to be more common than other inborn errors of metabolism and responds well to treatment with N-carbamyl-l-glutamate. Therefore, early identification of hyperammonaemia will allow specific treatment with N-carbamyl-l-glutamate and prevent neurological sequelae. Carbonic anhydrase VA deficiency should therefore be considered a treatable condition in the differential diagnosis of hyperammonaemia in neonates and young children.
(© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)
Databáze: MEDLINE
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