Ceramide synthase inhibition by fumonisins: a perfect storm of perturbed sphingolipid metabolism, signaling, and disease.

ABSTRACT: Fumonisins are mycotoxins that cause diseases of plants and, when consumed by animals, can damage liver, kidney, lung, brain, and other organs, alter immune function, and cause developmental defects and cancer. They structurally resemble sphingolipids (SLs), and studies nearly 30 years ago discovered that the most prevalent fumonisin [fumonisin B₁ (FB₁)] potently inhibits ceramide synthases (CerSs), enzymes that use fatty acyl-CoAs to N-acylate sphinganine (Sa), sphingosine (So), and other sphingoid bases. CerS inhibition by FB₁ triggers a "perfect storm" of perturbations in structural and signaling SLs that include: reduced formation of dihydroceramides, ceramides, and complex SLs; elevated Sa and So and their 1-phosphates, novel 1-deoxy-sphingoid b

SUBMITTER: Riley RT 

PROVIDER: S-EPMC6602133 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature