NAD(+) biosynthesis and salvage--a phylogenetic perspective.

Area of Science:

• Biochemistry
• Evolutionary Biology
• Molecular Biology

Background:

• Nicotinamide adenine dinucleotide (NAD) functions as a redox carrier and a signaling molecule.
• NAD(+) signaling pathways release nicotinamide (Nam), necessitating continuous NAD(+) pool replenishment.
• The evolutionary history of NAD(P) synthesis in eukaryotes remains largely unexplored.

Purpose of the Study:

• To investigate the evolutionary conservation and variation of NAD(P) biosynthetic pathways across eukaryotes.
• To identify ancestral NAD(P) synthesis routes and understand the distribution of nicotinamide (Nam) salvage pathways.

Main Methods:

• Bioinformatic analysis of genes involved in NAD(P) metabolism across 45 eukaryotic species.
• Comparative genomics to identify similarities and differences in NAD(P) synthesis pathways.

Main Results:

• The Preiss-Handler pathway and NAD(+) kinase were identified as universally conserved, suggesting ancestral roles in NAD(P) synthesis.
• Two distinct pathways for converting Nam to NAD(+) were found to coexist in several species, contrary to prior beliefs.
• Evidence suggests the co-evolutionary appearance of Nam N-methyltransferase, Nam phosphoribosyl transferase, and poly-ADP-ribosyltransferases.

Conclusions:

• The Preiss-Handler pathway and NAD(+) kinase represent ancient NAD(P) synthesis routes in eukaryotes.
• The presence of dual Nam salvage pathways in some species broadens our understanding of NAD(+) homeostasis.
• Phylogenetic analysis indicates parallel evolution of key enzymes in NAD(+) metabolism and signaling.