Metabolic Profiling of Alternative NAD Biosynthetic Routes in Mouse Tissues

Autor: Michele Di Stefano, Giulio Magni, Adolfo Amici, Giuseppe Orsomando, Silverio Ruggieri, Francesca Mazzola, Laura Conforti, Nadia Raffaelli, Valerio Mori
Rok vydání: 2014
Předmět:
B Vitamins
Metabolic Analysis
Physiology
Coenzymes
lcsh:Medicine
Biochemistry
Mice
chemistry.chemical_compound
NMNAT1
Biochemical Simulations
Medicine and Health Sciences
Nicotinamide-Nucleotide Adenylyltransferase
lcsh:Science
Enzyme Chemistry
chemistry.chemical_classification
Multidisciplinary
Vitamins
Animal Models
Enzymes
Bioassays and Physiological Analysis
medicine.anatomical_structure
Metabolic Pathways
Research Article
Mouse Models
Biology
Biosynthesis
Research and Analysis Methods
Niacin
Isozyme
Model Organisms
Transferases
Basal Metabolic Rate Measurement
medicine
Metabolomics
Animals
Nutrition
Enzyme Assays
lcsh:R
Biology and Life Sciences
Nutrients
NAD
In vitro
Small intestine
Mice
Inbred C57BL
Metabolism
Enzyme
chemistry
Enzymology
Cofactors (Biochemistry)
lcsh:Q
NAD+ kinase
Physiological Processes
Biochemical Analysis
Homeostasis
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 11, p e113939 (2014)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0113939
Popis: NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the "amidated" and "deamidated" routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT), which in mammals comprises three distinct isozymes, and NAD synthetase (NADS). First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes'rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme's substrate NaAD (nicotinic acid adenine dinucleotide). In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.
Databáze: OpenAIRE
Externí odkaz: