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måndag 9 mars 2020

Sivuhyppy NAD+ aineenvaihduntakarttaan.

NAD+ metabolia karttoja on minulla vihossa ja niitä tein kun luin sirtuiineista, sillä eräs sirtuiini osallistuu  ADPR- metaboliaan.
cADPR
https://en.wikipedia.org/wiki/Cyclic_ADP-ribose
ADPR
NAADP  (inhibiittori: diltiatsedm, dihydropyridiini)
NAAD
NADH
https://en.wikipedia.org/wiki/Nicotinic_acid_adenine_dinucleotide_phosphate

https://www.researchgate.net/figure/Mammalian-NAD-metabolic-pathways-The-biosynthesis-of-

Mammalian NAD metabolic pathways. The biosynthesis of NAD occurs through both de novo and salvage pathways (339). In mammalian cells, 90% of free tryptophan is metabolized through the kynurenine pathway, leading to the de novo synthesis of NAD. The three different salvage pathways start either from nicotinamide (Nam), nicotinic acid (Na), or nicotinamide riboside (NR). In mammals, the origin of nicotinic acid is mainly nutritional. Nicotinamide, a product of NAD hydrolysis, is first converted into nicotinamide mononucleotide (NMN) and then into NAD by nicotinamide phosphoribosyl transferase (NamPRT) and nicotinamide mononucleotide adenylyl transferases (Na/NMNAT-1,-2, and-3), respectively. Nicotinamide riboside was recently shown to serve as a precursor for NAD synthesis, connected to the Nam salvage pathway through NMN (36). Nicotinamide riboside is converted to NMN by the ATP-consuming nicotinamide riboside kinases 1 and 2 (NRK-1 and-2) (36). Nicotinic acid can be converted through the Preiss-Handler salvage pathway into nicotinic acid mononucleotide (NaNM) and nicotinate adenine dinucleotide by the concerted actions of nicotinic acid phosphoribosyl transferase (NaPRT) and Na/NMNAT-1,-2, and-3, respectively. Nicotinate adenine dinucleotide is directly transformed into NAD by the glutamine-hydrolyzing NAD synthetase (NADS). Na/NMNATs are ATP-consuming enzymes, using either NaMN or NMN as a substrate. Whether both NamPRT and NaPRT are also ATPconsuming enzymes in vivo is not certain. Thus, when the Preiss-Handler salvage pathway is used, the cell invests three or four molecules of ATP from Na to NAD , depending on whether NaPRT is also an ATP-consuming enzyme in vivo. In mammalian cells, under the conditions where NAD is used as a glycohydrolase substrate, the Nam salvage pathway is required, since there is no nicotinamidase to produce nicotinic acid. Depending on whether NamPRT uses one ATP molecule to convert Nam into NMN, the Nam salvage pathway consumes two or three ATP molecules from Nam to NAD. The de novo pathway is connected to the Preiss-Handler salvage pathway through NaMN. NAD can be hydrolyzed by various enzymatic activities, such as PARPs, MARTs, SIRTs, and ADP-ribosyl cyclases, which release the Nam moiety from NAD to produce poly-ADP-ribose, mono-ADP-ribosyl-protein, acetyl-ADP-ribose (O-AADPR), or cyclic-ADP-ribose (cADPR) and nicotinate adenine dinucleotide phosphate (NAADP), respectively. These products are then further metabolized by different hydrolase activities, yielding ADP-ribose (ADPR), which, in turn, can be transformed into 5-phosphribosyl-1-pyrophosphate (PRPP) by the ATP-consuming ADP-ribose pyrophosphatase (ARPP)/ribose phosphate pyrophosphokinase (RPPK) pathway. PRPP is used by the Nam salvage pathway enzymes NamPRT and NaPRT.

NAD-occurs-through-both-de-novo-and_fig1_6830373 

 https://www.researchgate.net/publication/235895284_Macrodomain-containing_proteins_are_new_mono-ADP-ribosylhydrolases..

Abstract
ADP-ribosylation is an important post-translational protein modification (PTM) that regulates diverse biological processes. ADP-ribosyltransferase diphtheria toxin-like 10 (ARTD10, also known as PARP10) mono-ADP-ribosylates acidic side chains and is one of eighteen ADP-ribosyltransferases that catalyze mono- or poly-ADP-ribosylation of target proteins. Currently, no enzyme is known that reverses ARTD10-catalyzed mono-ADP-ribosylation. Here we report that ARTD10-modified targets are substrates for the macrodomain proteins MacroD1, MacroD2 and C6orf130 from Homo sapiens as well as for the macrodomain protein Af1521 from archaebacteria. Structural modeling and mutagenesis of MacroD1 and MacroD2 revealed a common core structure with Asp102 and His106 of MacroD2 implicated in the hydrolytic reaction. Notably, MacroD2 reversed the ARTD10-catalyzed, mono-ADP-ribose-mediated inhibition of glycogen synthase kinase 3β (GSK3β) in vitro and in cells, thus underlining the physiological and regulatory importance of mono-ADP-ribosylhydrolase activity. Our results establish macrodomain-containing proteins as mono-ADP-ribosylhydrolases and define a class of enzymes that renders mono-ADP-ribosylation a reversible modification.
 
 

1 kommentar:

  1. I read that Post and got it fine and informative. Please share more like that...
    Nicotinamide mononucleotide

    SvaraRadera