Date published: 2025-9-17

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C5orf33 Activators

C5orf33 is an enzyme that plays a crucial role in the regulation of cellular NADP+ levels by catalyzing the phosphorylation of NAD+ to NADP+. The activity of this enzyme can be enhanced by increasing the availability of its substrate, NAD+. Precursors to NAD+, as well as compounds that upregulate the NAD+ salvage pathway, effectively boost the levels of NAD+ within cells, thereby facilitating the enzymatic action of C5orf33. Additionally, activators of AMP-activated protein kinase (AMPK) contribute to this process by stimulating the biosynthesis of NAD+, providing a larger pool of substrate for C5orf33 to act upon. The consequent rise in NADP+ production is critical for various anabolic processes, including fatty acid, nucleotide, and cholesterol synthesis.

Furthermore, certain compounds that influence mitochondrial biogenesis and function can indirectly promote the activity of C5orf33 by increasing the cellular demand for NADP+. This is due to the enzyme's location within mitochondria, where it fulfills the need for NADP+, necessary for the redox balance and proper functioning of the organelle. Compounds that modulate intracellular calcium levels also play a role in activating C5orf33, potentially via calcium/calmodulin-dependent kinases that can phosphorylate and activate mitochondrial enzymes. By ensuring ample NADP+ supply, C5orf33 is central to maintaining cellular redox states and metabolism by catalyzing the conversion of NAD+ to NADP+. The functional activity of C5orf33 can be enhanced through the elevation of intracellular NAD+ levels, which serves as the substrate for the enzyme. This elevation can be achieved by compounds that either supply NAD+ directly or promote its synthesis through activation of NAD+ biosynthetic pathways. For instance, compounds that activate sirtuins or AMPK can lead to a higher NAD+ turnover or biosynthesis, respectively. This upsurge in NAD+ levels is a direct driver for C5orf33, enabling it to produce more NADP+, which is indispensable for anabolic reactions and redox balance in the cell, especially within mitochondria.

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