5′-Nucleotidase Plays a Key Role in Uric Acid Metabolism of Bombyx mori

Abstract

Uric acid (UA) is the end-product in the human purine metabolism pathway. The UA that accumulates in silkworm tissues is excreted as a nitrogen waste product. Here, we first validated that Bombyx mori has a homolog of the human gene that encodes the 5′-nucleotidase (5′N) involved in purine metabolism. The B. mori gene, Bm5′N, is located upstream of other genes involved in UA metabolism in the silkworm. Disruption of Bm5′N via the CRISPR/Cas9 system resulted in decreased UA levels in the silkworm epidermis and caused a translucent skin phenotype. When Bm5′N mutant silkworms were fed with the uric acid precursor inosine, the UA levels in the epidermis increased significantly. Furthermore, the metabolomic and transcriptomic analyses of Bm5′N mutants indicated that loss of the Bm5′N affected purine metabolism and the ABC transport pathway. Taken together, these results suggest that the UA pathway is conserved between the silkworm and humans and that the Bm5′N gene plays a crucial role in the uric acid metabolism of the silkworm. Thus, the silkworm may be a suitable model for the study of UA metabolism pathways relevant to human disease.

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori

“…To determine the key metabolic pathways in silkworms' resistance to BmNPV, the survival rate of BmNPV‐infected op50 after feeding with five metabolites from the candidate metabolic pathways was determined; these were inosine, glucose, taurine, IF + FA and serine. Inosine participates in purine metabolism to synthesise uric acid (Fujii et al, 2020; Tang et al, 2021). Glucose enters the TCA cycle through glycolysis, and fumaric acid (IF) is an important raw material in the TCA cycle (Araujo et al, 2011).…”

Bioactive Compounds in Garlic (Allium sativum) and Black Garlic as Antigout Agents, Using Computer Simulation

“…Uric acid in the body is produced through the action of several enzymes, such as xanthine oxidase (XO) [ 5 ], adenine deaminase (ADA), guanine deaminase (GDA) [ 7 ], purine nucleoside phosphorylase (PNP) [ 8 ], and 5-nucleotidase II. (NT5C2) [ 9 ]. The mechanism of uric acid formation can be seen in the Supplementary Materials , Figure S4 .…”

“…XDH acts on these same substrates but utilizes NAD as a cofactor to produce NADH instead of ·O 2 − and uric acid [ 6 ]. Apart from inhibiting the action of the XO enzyme, this can also be achieved by inhibiting adenine deaminase (ADA), guanine deaminase (GDA) [ 7 ], purine nucleoside phosphorylase (PNP) [ 8 ], and 5-nucleotidase II (NT5C2) [ 9 ]. The clinical treatment for gout sufferers is to give drugs such as allopurinol and febuxostat, but these drugs have side effects, such as kidney toxicity, liver necrosis, and allergic reactions [ 10 ].…”

Nitrogen Acquisition Strategies Mediated by Insect Symbionts: A Review of Their Mechanisms, Methodologies, and Case Studies

“…Similar to D. melanogaster, the blowfly Lucilia sericata express high levels of urate oxidase in the malpighian tubules that convert uric acid from the hemolymph into allantoin that is excreted [81,83]. The uric acid that accumulates in silkworm tissues is excreted as a nitrogen waste product, but the genes of Bmwh3, BmABCG5, and Bm5 N encoded by silkworm are involved in uric acid metabolism [84]. Interestingly, urease in fresh mulberry leaves can directly pass through the gut wall of silkworm larvae into the hemolymph without being digested.…”