Galactose 1-phosphate (Gal-1-P) is the substrate of galactose 1-phosphate uridylyltransferase (GALT), which is cytotoxic and has inhibitory effect on many enzymes in glucose metabolism pathway[1,2].Gal-1-P(1-16 mM;37℃；1h) can stimulated rat brain Na+,K+-ATPase[3].
Gal-1-P (5-10 mM) in culture medium for 7-14 days significantly decreased IGF-1, PDGF and FBS-stimulated DNA synthesis in Fibroblasts[4]. Various concentrations (1-16 mM) of galactose-1-phosphate (Gal-1-P) were preincubated with brain homogenates of suckling rats as well as with pure eel Electroforus electricus AChE at 37℃ for 1 h. Gal-1-P decreased gradually the enzyme activity reaching a plateau, when incubated with 8-16 mM. Gal-1-P can affect acetylcholine degradation acting directly on AChE molecule[5].
References:
[1]. Oh SL, Cheng LY, et,al. Galactose 1-phosphate accumulates to high levels in galactose-treated cells due to low GALT activity and absence of product inhibition of GALK. J Inherit Metab Dis. 2020 May;43(3):529-539. doi: 10.1002/jimd.12198. Epub 2019 Dec 17. PMID: 31774565.
[2]. Lai K, Langley SD, et,al. GALT deficiency causes UDP-hexose deficit in human galactosemic cells. Glycobiology. 2003 Apr;13(4):285-94. doi: 10.1093/glycob/cwg033. Epub 2003 Jan 3. PMID: 12626383.
[3]. Tsakiris S, Marinou K, et,al. The effect of galactose metabolic disorders on rat brain Na+,K+-ATPase activity. Z Naturforsch C J Biosci. 2002 Sep-Oct;57(9-10):939-43. doi: 10.1515/znc-2002-9-1030. PMID: 12440737.
[4]. Al-Essa M, Dhaunsi G. Receptor-mediated attenuation of insulin-like growth factor-1 activity by galactose-1-phosphate in neonate skin fibroblast cultures: Galactosemia pathogenesis. Adv Clin Exp Med. 2020 Apr;29(4):499-504. doi: 10.17219/acem/111807. PMID: 32356415.
[5]. Tsakiris S, Schulpis KH. The effect of galactose metabolic disorders on rat brain acetylcholinesterase activity. Z Naturforsch C J Biosci. 2000 Sep-Oct;55(9-10):852-5. doi: 10.1515/znc-2000-9-1032. PMID: 11098845.
半乳糖1磷酸是半乳糖-1-磷酸尿苷酰转移酶(GALT)的作用底物,具有细胞毒性,对糖代谢途径中的多种酶有抑制作用[1,2].
Gal-1-P(1- 16mm;37℃;1h)能刺激大鼠脑Na+,K+-ATP酶[3]。Gal-1-P (5-10 mM；7-14天)在培养基中显著降低成纤维细胞中IGF-1、PDGF和FBS刺激的DNA合成[4]。
将不同浓度(1 ~ 16 mM)的半乳糖-1-磷酸(Gal-1-P)与乳鼠脑匀浆及纯电鳗乙酰胆碱(AChE)在37℃下孵育1 h, Gal-1-P在8 ~ 16 mM孵育1 h后, 酶活性逐渐降低至稳定。并且Gal-1-P可直接作用于乙酰胆碱分子[5]。