CD38 mediates nicotinamide mononucleotide (NMN) base exchange to yield nicotinic acid mononucleotide (NaMN)

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Abstract Nicotinamide mononucleotide (NMN) is a widely investigated metabolic precursor to the prominent redox cofactor nicotinamide adenine dinucleotide (NAD + ), where it assumed that delivery of this compound results in its direct incorporation into NAD via canonical salvage / recycling pathway. Surprisingly, treatment with pathway intermediate leads increases nicotinic acid (NaMN) and (NaAD), two members Preiss-Handler de novo pathways. In mammals, these pathways are not known intersect prior production . Here, we show cell surface enzyme CD38 can mediate base exchange reaction on NMN, whereby ring exchanged free yield NaMN, vivo small molecule inhibition abolishing NMN-induced increase NaMN NaAD. Together, data demonstrate new mechanism by which intermediates mammalian biosynthesis.

Language: Английский

Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan

Published: Sept. 26, 2024

The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries gametes across lifespan. Ovaries exhibit localized structural cell-type specific enrichment both follicular extrafollicular environments. Moreover, oocytes harbor panel long-lived including cytoskeletal, mitochondrial, oocyte-derived proteins. exceptional persistence these molecules suggest critical role lifelong maintenance age-dependent tissues.

Language: Английский