China
Africa
Explore chapters and articles related to this topic
Serine deficiencies
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The patient with phosphoserine phosphatase deficiency [16] had pre- and postnatal retardation of growth, psychomotor retardation and features of Williams syndrome, which was considered to be unrelated, although both genes are on chromosome 7.
Colon Carcinogenesis: Biochemical Changes
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Young S. Kim, Laurence J. Mcintyre
Several other enzymes have been investigated to determine whether changes occur during colon carcinogenesis. Because of the close relationship mentioned previously between cancer and the expression of fetal cellular phenotypes, Herzfeld and Greengard31have compared the levels of several enzymes in normal human colon tissue with the levels in colon adenocarcinomas and in fetal colon. Many of the enzymes measured showed a parallel divergence in fetal and neoplastic colon from the differentiated adult tissue. The enzymes elevated in neoplastic tissue are those necessary for rapid cellular growth and include some of the enzymes of nucleic acid and carbohydrate metabolism, listed previously, as well as peptidyl proline hydroxylase, which is involved in collagen production, and pyrroline-5-carboxylate reductase and phosphoserine phosphatase which are involved in nonessential amino acid production. Plasminogen activator is an enzyme which has received considerable attention in recent years in studies of cellular transformation in vitro. A rise in the cellular enzyme level may often accompany transformation by a variety of agents. For this reason Corasanti et al.32 measured the levels of plasminogen activator in human colonic mucosa and in colon adenocarcinoma. They found elevated levels of the enzyme in tumor tissue. The activator in the colon tumors was predominantly urokinase-like, while that in normal colon contained at least two forms of the enzyme. There was also a correlation between the ratios of plasminogen activator activity in tumor and normal tissue and the presence of signs of invasiveness and metastasis. It is suggested that the enzyme could be involved in release of tumor cells from the primary tumor or in inhibiting the movement of host macrophages.
Recent developments in the pathobiology of lung myofibroblasts
Published in Expert Review of Respiratory Medicine, 2021
Dingyuan Jiang, Tapan Dey, Gang Liu
Glycolytic pathway diverts at some of the 10 steps, which produce intermediates to be used for the syntheses of serine, nucleotides, and lipids. The de novo serine synthesis is mediated by a cascade of enzymes, including Phosphoglycerate dehydrogenase (PHGDH), phosphohydroxythreonine aminotransferase (PSAT), and phosphoserine phosphatase (PSPH). The newly synthesized serine is then converted to glycine through the activity of serine hydroxymethyltransferase (SHMT) [50]. Recent studies found an elevated expression of all of these enzymes in TGF-β1 induced lung myofibroblasts, which is largely dependent on the mammalian target of rapamycin complex 1 (mTORC1) induced transcriptional factor activating transcription factor 4 (ATF4) [51–53]. The increased expression of these enzymes inevitably led to an uptick in the de novo serine/glycine synthesis, which was demonstrated to be required for an excessive production of collagens, the key characteristic of myofibroblasts [51–54]. Such a large demand for glycine is necessitated likely due to the disproportionately high content of this amino acid in most types of collagens [51–53]. More importantly, suppression of the de novo serine/glycine synthesis by a PHGDH inhibitor has also been found to be effective in treating lung fibrosis in mouse models [55].
Prenatal genetic diagnosis of Neu-Laxova syndrome
Published in Journal of Obstetrics and Gynaecology, 2018
Amber M. Wood, Amy T. Mottola, Eleanor H. Rhee, Jeffrey A. Kuller
Neu-Laxova has been recognised as a clinical syndrome since 1971 (Neu et al. 1971). Findings on ultrasound and postnatal autopsy include ichthyosis, severe intrauterine growth restriction, microcephaly, CNS abnormalities, limb deformities and abnormal facial features, and the syndrome is considered lethal (Manning et al. 2004; Coto-Puckett et al. 2010; Shaheen et al. 2014). Previously, diagnosis was based on a clinical constellation of findings on autopsy as no molecular genetic testing options were available. In 2014, a gene mapping study in three consanguineous families affected by NLS identified a mutation in the PHGDH gene (Shaheen et al. 2014). NLS caused by mutations in the PHGDH gene is termed NLS1 (MIM 256520). Two additional mutations in phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH) have been identified (Acuna-Hidalgo et al. 2014). NLS caused by mutations in the PSAT1 gene is categorised as NLS2 (MIM 616038) and the clinical phenotype is similar to NLS1.
Phosphoglycerate dehydrogenase (PHGDH) inhibitors: a comprehensive review 2015–2020
Published in Expert Opinion on Therapeutic Patents, 2021
Quentin Spillier, Raphaël Frédérick
The serine synthetic pathway (SSP) is a particularly important branch of glycolysis (Figure 1). It consists of three consecutive enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT-1) and phosphoserine phosphatase (PSPH). This biosynthetic pathway is responsible for the production of a non-essential amino acid, serine, from the glycolytic intermediate 3-phosphoglyceric acid (3-PG) but also for the production of an equimolar amount of reduced nicotinamide adenine dinucleotide (NADH) and α-ketoglutarate (α-KG). In brief, the SSP is involved in diverse cellular processes including methylation reactions, antioxidant production, lipid head group modifications, and nucleotide metabolism [6].