Gulo, also known as gluconolactone oxidase, is the rate-limiting enzyme in Vitamin C synthesis in plants and some mammals. Glucose serves as the precursor for Vitamin C synthesis, and Gulo is crucial in this pathway. Vitamin C is a potent antioxidant that protects cells and tissues from oxidative damage, thus Gulo is of great biological importance in maintaining antioxidant defense mechanisms [1].

In Gulo(-/-) mice, which cannot synthesize vitamin C due to a defect in Gulo expression, extensive oxidative stress and increased inflammation were found in the colon. There was also decreased IL-22 production, impaired NKp46(+) cell recruitment, and p38MAPK pathway activation. Additionally, mucin-1 expression decreased, IL-6 production increased, and the STAT3 and Akt pathways were activated. These results suggest that vitamin C insufficiency, caused by Gulo deficiency, can lead to severe colitis, indicating that Gulo-mediated vitamin C synthesis may play a preventive role in regulating cytokine production and inflammation [2].

In conclusion, Gulo is essential for vitamin C synthesis, which is key for antioxidant protection. The study of Gulo(-/-) mouse models reveals its role in maintaining normal colonic conditions and regulating inflammatory responses, contributing to our understanding of the mechanisms underlying colitis and potentially other diseases related to oxidative stress and inflammation.

References:

1. Sivadas, Sneha, Mohanty, Amaresh Kumar, Rajesh, Saranga, Muthuvel, Suresh Kumar, Vasanthi, Hannah R. 2023. Molecular modelling and biological evaluation of phyto-molecules as potential activators of gluconolactone oxidase (GULO). In Journal of biomolecular structure & dynamics, 41, 15124-15136. doi:10.1080/07391102.2023.2187227. https://pubmed.ncbi.nlm.nih.gov/36883880/

2. Jo, Hyejung, Lee, Dahae, Go, Cheolhyeon, Kim, Yejin, Kang, Jae Seung. 2022. Preventive Effect of Vitamin C on Dextran Sulfate Sodium (DSS)-Induced Colitis via the Regulation of IL-22 and IL-6 Production in Gulo(-/-) Mice. In International journal of molecular sciences, 23, . doi:10.3390/ijms231810612. https://pubmed.ncbi.nlm.nih.gov/36142515/