CA VB

CA VB (CA5B) is a mitochondrial carbonic anhydrase isoform that catalyzes CO₂ hydration to support bicarbonate-dependent metabolism^[1][2]. Mechanistically, CA VB contributes to Krebs cycle anaplerosis by supporting mitochondrial oxaloacetate synthesis in pancreatic β cells^[3]. In mouse islets and Min6 β cells, thiazides inhibited glucose- and sulfonylurea-stimulated insulin secretion through CA5B inhibition^[3]. CA5B knockout mice resisted thiazide-induced glucose intolerance, which identifies CA VB as the functional thiazide-sensitive isoform in this β-cell model^[3]. Compared with CA VA, CA VB shows broader tissue distribution, whereas CA VA is most highly expressed in liver and has a predominant role in ammonia detoxification^[2]. This isoform distinction matters because CA5A sequencing identified disease-causing variants in early-onset metabolic crisis, while the same cohort found none in CA5B^[4]. CA VB also differs pharmacologically from CA VA, because human CA VB shows greater sensitivity to anion inhibitors and a distinct bicarbonate inhibition profile^[5]. For experimental applications, CA VA/VB inhibitors reduced paclitaxel-induced neuropathic pain and improved mitochondrial dysfunction in mice^[6]. In cerebrovascular models, CA VB inhibition or deletion reduced amyloid- and tau-linked endothelial dysfunction, BBB disruption, and inflammatory activation^[7].