ArticleProceedings of the National Academy of Sciences of the United States of America2013
Targeted mutagenesis of mitochondrial carbonic anhydrases VA and VB implicates both enzymes in ammonia detoxification and glucose metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models.Science advances · 2026Article
- Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models.bioRxiv : the preprint server for biology · 2026Article
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- A founder mutation inJIMD reports · 2024Article
- Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH.Pharmaceuticals (Basel, Switzerland) · 2024Article
- CBFA2T3 Is PPARA Sensitive and Attenuates Fasting-Induced Lipid Accumulation in Mouse Liver.Cells · 2024Article
- Characterizing the metabolic divide: distinctive metabolites differentiating CAD-T2DM from CAD patients.Cardiovascular diabetology · 2024Article
- Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease.The Journal of physiology · 2023Review
- Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins inInternational journal of molecular sciences · 2021Article
- Carbonic Anhydrases as Potential Targets Against Neurovascular Unit Dysfunction in Alzheimer's Disease and Stroke.Frontiers in aging neuroscience · 2021Review
- Inflammation-Induced Lactate Leads to Rapid Loss of Hepatic Tissue-Resident NK Cells.Cell reports · 2020Article
- Transgenic expression of carbonic anhydrase III in cardiac muscle demonstrates a mechanism to tolerate acidosis.American journal of physiology. Cell physiology · 2019Article
- Carbonic anhydrases as disease markers.Expert opinion on therapeutic patents · 2019Review
- Design, Synthesis, and X-ray of Selenides as New Class of Agents for Prevention of Diabetic Cerebrovascular Pathology.ACS medicinal chemistry letters · 2018Article
- Carbonic Anhydrases: Role in pH Control and Cancer.Metabolites · 2018Review
- Regulation of high glucose-induced apoptosis of brain pericytes by mitochondrial CA VA: A specific target for prevention of diabetic cerebrovascular pathology.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Article
- Defective hepatic bicarbonate production due to carbonic anhydrase VA deficiency leads to early-onset life-threatening metabolic crisis.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Article
- Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats.Balkan medical journal · 2016Article
- Protective Effect of Topiramate on Hyperglycemia-Induced Cerebral Oxidative Stress, Pericyte Loss and Learning Behavior in Diabetic Mice.International library of diabetes & metabolism · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Prior studies with carbonic anhydrase (CA) inhibitors implicated mitochondrial CA in ureagenesis and gluconeogenesis. Subsequent studies identified two mitochondrial CAs. To distinguish the contribution of each enzyme, we studied the effects of targeted disruption of the murine CA genes, called Car5A and Car5B. The Car5A mutation had several deleterious consequences. Car5A null mice were smaller than wild-type littermates and bred poorly. However, on sodium-potassium citrate-supplemented water, they produced offspring in expected numbers. Their blood ammonia concentrations were markedly elevated, but their fasting blood sugars were normal. By contrast, Car5B null mice showed normal growth and normal blood ammonia levels. They too had normal fasting blood sugars. Car5A/B double-knockout (DKO) mice showed additional abnormalities. Impaired growth was more severe than for Car5A null mice. Hyperammonemia was even greater as well. Although fertile, DKO animals were produced in less-than-predicted numbers even when supplemented with sodium-potassium citrate in their drinking water. Survival after weaning was also reduced, especially for males. In addition, fasting blood glucose levels for DKO mice were significantly lower than for controls (153 ± 33 vs. 230 ± 24 mg/dL). The enhanced hyperammonemia and lower fasting blood sugar, which are both seen in the DKO mice, indicate that both Car5A and Car5B contribute to both ammonia detoxification (ureagenesis) and regulation of fasting blood sugar (gluconeogenesis). Car5A, which is expressed mainly in liver, clearly has the predominant role in ammonia detoxification. The contribution of Car5B to ureagenesis and gluconeogenesis was evident only on a Car5A null background.
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