嘌呤核苷酸的从头合成途径首先要合成IMP，后者可以转化为AMP和GMP。 IMP的合成从PRPP（磷酸核糖焦磷酸）开始，共10步，先生成咪唑环，再生成次黄嘌呤。 PRPP由5-磷酸核糖与ATP在磷酸核糖焦磷酸激酶（也称PRPP合成酶）催化下生成，相当于磷酸核糖的活化形式。 PRPP的合成。 引自themedicalbiochemistrypage. 第一步反应由谷氨酰胺的氨基取代焦磷酸，开始在磷酸核糖之上构建咪唑环。 之后依次连接甘氨酸、甲川基和氨基后环化，生成5-氨基咪唑核 …

2023年11月13日 · We propose an integrated model of how NAD + regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy. NAD +, an essential metabolite and co-enzyme, assumes two...

Inosine 5′-monophosphate dehydrogenase (IMPDH) is a purine biosynthetic enzyme that catalyzes the nicotinamide adenine dinucleotide (NAD +)-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the first committed and rate-limiting step towards the de novo biosynthesis of guanine nucleotides from IMP.

1996年6月14日 · The IMPDH catalyzed oxidation of IMP results in transfer of hydrogen to the nicotinamide ring of NAD, forming NADH and XMP. Since direct transfer of the hydride is energetically unfavorable, two mechanisms involving activation of IMP at the inosine C2 position have been proposed ( Hedstrom and Wang 1990 ).

2016年11月3日 · 次黄嘌呤单核苷酸脱氢酶 (inosine 5'-mono­phosphate dehydrogenase，IMPDH) 是一种烟酰胺腺嘌呤二核苷酸 (nicotinamide adenine dinucleotide，NAD +) 依赖酶，广泛存在于全身各分化细胞 [1]。 IMPDH是嘌呤代谢过程中的限速酶，可催化次黄嘌呤核苷酸 (inosinemonphosphate，IMP) 转化生成黄嘌呤核苷酸 (xanthosine monophosphate，XMP) [2]，继而合成鸟嘌呤核苷酸，在细胞的生长、分化和凋亡中起着重要作用。 同时IMPDH也是细胞免 …

2024年11月12日 · On chromatin, IMPDH2 interacts with and modulates PARP1 activity by controlling the nuclear availability of NAD + to fine-tune the DNA damage response. However, when IMPDH2 is restricted to the nucleus, it depletes nuclear NAD +, leading to PARP1 cleavage and cell death. Our study identifies a non-canonical nuclear role for IMPDH2, acting as a ...

IMP is the product of de novo purine nucleotide biosynthesis and the precursor to both adenine and guanine nucleotides (Scheme 1). The IMPDH-catalyzed conversion of IMP to XMP is the first committed and rate-limiting step in guanine nucleotide biosynthesis. XMP is subsequently converted to GMP by the action of GMP synthetase (GMPS).

2024年12月1日 · We found that SIRT5 can directly interact with IMPDH1 and promotes desuccinylation on the N terminal of IMPDH1, thereby leading to increased IMPDH enzymatic activity, enhanced purine biosynthesis and promoted cell proliferation.

2024年11月12日 · Our study identifies a non-canonical nuclear role for IMPDH2, acting as a convergence point of nuclear metabolism and DNA damage response. Oncogenic signals orchestrate a metabolic rewiring that...

Inosine monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to XMP with the concomitant reduction of NAD to NADH. This reaction is the rate-limiting step in guanine nucleotide biosynthesis. IMPDH is a proven target for immunosuppressive, anticancer and antiviral chemotherapy, and may …