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Deamidation sites of G6PD and PHGDH catalyzed by CAD

ABSTRACT: CAD interacts with and deamidates glucose-6-phosphate dehydrogenase (G6PD) and phosphoglycerate dehydrogenase (PHGDH), which are rate-limiting enzymes of the PPP and SSP, respectively. Here we identified G6PD and PHGDH deamidation sites by mass spectrometry.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Chao Qin

LAB HEAD: Pinghui Feng

PROVIDER: PXD052165 | Pride | 2026-02-03

REPOSITORIES: Pride

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Project description:D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion. Experiment Overall Design: Total RNA samples were prepared from head tissues from 2 embryos of Phgdh knockout and littermate wild-type controls. Experiment Overall Design: RNA of 4 biological replicates was hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

			Action	DRS
	20220730-Chao-CAD-PHGDH.msf	Msf
	20220730-Chao-CAD-PHGDH.raw	Raw
	20220730-Chao-EV-PHGDH.msf	Msf
	20220730-Chao-EV-PHGDH.raw	Raw
	CAD-G6PD.msf	Msf

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Deamidation sites of G6PD and PHGDH catalyzed by CAD

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