• Finally, the rescue of the DCM phenotypes was mediated by the activating transcription factor 4 (ATF4) and its downstream effector genes, phosphoglycerate dehydrogenase (PHGDH), which encodes a critical enzyme of the serine biosynthesis pathway, and Tribbles 3 (TRIB3), a pseudokinase with pleiotropic cellular functions. (bvsalud.org)
  • A combination of SMKIs ameliorated contractile and metabolic dysfunction in DCM iPSC-CMs mediated via the ATF4-dependent serine biosynthesis pathway. (bvsalud.org)
  • Metabolomic analyses by UPLC-MS/MS reveal that the temporal concentrations of arginine, serine, tyrosine, and alanine are significantly higher in host ( Chilo suppressalis ) hemolymph at 3 days after parasitism, whereas the temporal levels of 5-hydroxylysine, glutamic acid, methionine, and lysine are significantly lower. (biomedcentral.com)
  • OGT transfers O-GlcNAc moieties from UDP-GlcNAc to serine and threonine residues of proteins and O-GlcNAcase (OGA) catalyzes the opposite reaction to remove O-GlcNAc. (nature.com)
  • While serine/threonine kinases all phosphorylate serine or threonine residues in their substrates, they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site, which together comprise the consensus sequence . (cloudfront.net)
  • R. (2017) Studying the function of the phosphorylated pathway of serine biosynthesis in Arabidopsis thaliana . (uni-koeln.de)
  • Arabidopsis PHOSPHOGLYCERATE DEHYDROGENASE1 of the phosphoserine pathway is essential for development and required for ammonium assimilation and tryptophan biosynthesis. (uni-koeln.de)
  • Phosphoserine aminotransferase (PSA) also known as phosphohydroxythreonine aminotransferase (PSAT) is an enzyme that in humans is encoded by the PSAT1 gene. (wikipedia.org)
  • The protein encoded by this gene is likely a phosphoserine aminotransferase, based on similarity to proteins in mouse, rabbit, and Drosophila. (wikipedia.org)
  • Homozygous or compound heterozygous mutations in PSAT1 cause Neu-Laxova syndrome and phosphoserine aminotransferase deficiency. (wikipedia.org)
  • Our multi-omics approach revealed that the serine/threonine kinase liver-associated kinase B1 (LKB1) couples mitochondrial function to cytokine expression in TH17 cells by regulating TCA cycle metabolism and transcriptional remodelling. (bvsalud.org)
  • The combinatorial SMKI treatment upregulated the expression of genes that encode serine, glycine, and one-carbon metabolism enzymes and significantly increased the intracellular levels of glucose-derived serine and glycine in DCM iPSC-CMs. (bvsalud.org)
  • Gerlich S.C., Walker B.J., Krueger S., Kopriva S. (2018) Sulfate metabolism in C4 flaveria species is controlled by the root and connected to serine biosynthesis. (uni-koeln.de)
  • Serine in plants: biosynthesis, metabolism, and functions. (uni-koeln.de)
  • Parviz M, Vogel K, Gibson KM, Pearl PL. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. (healthmatters.io)
  • These metabolic disorders are typically caused by genetic mutations that result in the impairment or deficiency of enzymes involved in the metabolism of β-alanine or related pathways. (healthmatters.io)
  • Moreover, glutamic acid is associated with N-acetylglutamate synthetase deficiency, which is an inborn error of metabolism. (foodb.ca)
  • These disorders result in the accumulation or the deficiency of 1 or more amino acids in biological fluids, which leads to the clinical signs and symptoms of the particular amino acid disorder. (marshfieldlabs.org)
  • LKB1 deletion restores IL-17 expression in TH17 cells with disrupted mitochondrial membranes, rectifying aberrant TCA cycle glutamine flux, balancing NADH/NAD+ and preventing 2-hydroxyglutarate production from the promiscuous activity of the serine biosynthesis enzyme phosphoglycerate dehydrogenase (PHGDH). (bvsalud.org)
  • is a kinase enzyme , in particular a protein kinase , that phosphorylates the OH group of the amino-acid residues serine or threonine , which have similar side chains. (cloudfront.net)
  • Types include those acting directly as membrane-bound receptors ( Receptor protein serine/threonine kinase ) and intracellular kinases participating in Signal transduction . (cloudfront.net)
  • D-serine action requires binding to neuronal NMDA-type glutamate receptors. (ox.ac.uk)
  • The article presents a clinical case of focal epilepsy with a status course of seizures associated with a genetic mutation in exon 1 of the PNPO gene, which led to pyridoxamine-5'-phosphate oxidase deficiency. (jmedcasereportsimages.org)
  • Code errors leading to a lack of pyridoxal-5'-phosphate manifest as B6-dependent epilepsy, including pyridoxamine-5-phosphate oxidase (PNPO) deficiency, which affects the synthesis and recycling of pyridoxal-5'-phosphate [2,3]. (jmedcasereportsimages.org)
  • to analyze the course of epilepsy with pyridoxamin-5'-phosphate oxidase deficiency in an 8-year-old patient with diagnosis verification by clinical exome sequencing. (jmedcasereportsimages.org)
  • Background Serine synthesis defects, characterized by developmental delay and seizures, have been described in children. (jamanetwork.com)
  • Objective To describe a case of serine synthesis defect due to 3-phosphoglycerate dehydrogenase deficiency in an adult with prominent chronic polyneuropathy. (jamanetwork.com)
  • Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila. (ox.ac.uk)
  • Although treatment of pyridoxal 5'-phosphate deficiency can successfully control seizures, most patients develop some degree of disability, regardless of early diagnosis and treatment. (jmedcasereportsimages.org)
  • We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPAR α , leading to its activation and significant reductions in serum lipid levels. (hindawi.com)
  • Recently, we demonstrated that deficiency or inhibition of AR caused significant dephosphorylation of hepatic PPAR α , leading to the activation of this transcriptional factor as well significant reduction in serum TG levels in streptozotocin-(STZ-) diabetic mice, an experimental model for type I diabetes mellitus (T1DM) [ 17 ]. (hindawi.com)
  • Not all patients with homocystinuria and prolidase deficiency will be detected by this assay. (marshfieldlabs.org)
  • Astray synthesizes the gliotransmitter D-serine, and vesicular release from astrocytes is required for drinking. (ox.ac.uk)
  • We propose that thirst elevates astrocytic D-serine release, which awakens quiescent glutamatergic circuits to enhance water procurement. (ox.ac.uk)
  • TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells. (aai.org)
  • Case reports of PLP deficiency, verified not only clinically, but also by exome sequencing, are quite rare as well as the methods for studying molecular markers of alpha-aminoadipic semialdehyde and pipecolic acid in body fluids [5-7]. (jmedcasereportsimages.org)
  • Screening the regulated genes revealed astrocytic expression of the astray-encoded phosphoserine phosphatase to bi-directionally regulate water consumption. (ox.ac.uk)
  • Phosphoserine phosphatase (PSPH) is one of the key enzymes of the L-serine synthesis pathway. (molcells.org)
  • In recent years patients have been identified with defects in the three enzymes of the L-serine pathway and almost invariably they presented with serious neurological symptoms consisting of psychomotor retardation, microcephaly and seizures. (mhmedical.com)
  • Serine is a nonessential amino acid generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), and phosphoserine phosphatase (PSPH). (nih.gov)
  • Upon measuring the phosphatase activity of PSPH on a serine-phosphorylated peptide, we found that PSPH dephosphorylated phospho-serine in peptide sequences. (molcells.org)
  • Reductive amination (transamination) of this ketone by phosphoserine transaminase (EC 2.6.1.52 ) yields 3-phosphoserine ( O -phosphoserine) which is hydrolyzed to serine by phosphoserine phosphatase (EC 3.1.3.3 ). (iiab.me)
  • The diagnosis of a serine deficiency disorder is established in a proband with biallelic pathogenic variants in PHGDH , PSAT1 , or PSPH identified by molecular genetic testing . (nih.gov)
  • PSPH is reported to affect the progression and survival of several cancers in an L-serine synthesis-independent manner, but the mechanism remains elusive. (molcells.org)
  • We demonstrate that PSPH promotes lung cancer progression through a noncanonical L-serine-independent pathway. (molcells.org)
  • Interestingly, L-serine had no effect on the altered invasion and colony formation by PSPH. (molcells.org)
  • studying the functional details of the L-serine-independent pathway of PSPH will be useful to understand cancer progression. (molcells.org)
  • In murine tumors, Apc status was identified as a determinant of the expression of genes controlling serine synthesis. (nih.gov)
  • Inhibition of serine synthesis enhanced the transcriptional changes following exogenous serine removal as well as alterations associated with DNA damage. (nih.gov)
  • Cysteine synthesis from serine. (iiab.me)
  • Historically two pathways of L-serine synthesis were identified: a phosphorylated pathway involving 3-phosphoglycerate, phospho-hydroxypyruvate, phosphoserine and L-serine, and a non-phosphorylated pathway involving D-glycerate, hydroxypyruvate and L-serine ( Figure 119-1 ). (mhmedical.com)
  • Combining genetic deletion of PSAT1 with exogenous serine deprivation maximally suppressed the proliferation of colorectal cancer cells and induced profound metabolic defects including diminished nucleotide production. (nih.gov)
  • Restricting endogenous and exogenous serine in vitro augmented 5-FU-induced cell death, DNA damage, and metabolic perturbations, likely accounting for the observed antitumor effect. (nih.gov)
  • This disorder of serine biosynthesis has been identified in two siblings who showed low concentrations of serine and glycine in plasma and cerebrospinal fluid. (nih.gov)
  • Clinically, the index patient presented with intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200 mg/kg/d) from age 11 wk. (nih.gov)
  • glycine supplementation with L-serine has been used in some individuals. (nih.gov)
  • Serine hydroxymethyltransferase (SHMT = serine transhydroxymethylase) also catalyzes the reversible conversions of L -serine to glycine (retro-aldol cleavage) and 5,6,7,8-tetrahydrofolate to 5,10-methylenetetrahydrofolate (mTHF) (hydrolysis). (iiab.me)
  • Industrially, L -serine is produced from glycine and methanol catalyzed by hydroxymethyltransferase. (iiab.me)
  • Serine (symbol Ser or S ) [3] [4] is an ɑ-amino acid that is used in the biosynthesis of proteins. (iiab.me)
  • In enzymology , the term serine/threonine protein kinase describes a class of enzymes in the family of transferases , that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins . (cloudfront.net)
  • At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK). (cloudfront.net)
  • Serine/threonine kinases play a role in the regulation of cell proliferation, programmed cell death ( apoptosis ), cell differentiation, and embryonic development. (cloudfront.net)
  • While serine/threonine kinases all phosphorylate serine or threonine residues in their substrates, they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site, which together comprise the consensus sequence . (cloudfront.net)
  • Types include those acting directly as membrane-bound receptors ( Receptor protein serine/threonine kinase ) and intracellular kinases participating in Signal transduction . (cloudfront.net)
  • If both parents are known to be heterozygous for a serine deficiency-causing pathogenic variant , each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier , and a 25% chance of inheriting neither of the familial pathogenic variants. (nih.gov)
  • It catalyzes magnesium-dependent hydrolysis of L-phosphoserine and is also involved in an exchange reaction between L-serine and L-phosphoserine. (nih.gov)
  • Once the serine deficiency-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible. (nih.gov)
  • Both loss of PSAT1 and removal of serine from the diet were necessary to suppress colorectal cancer xenograft growth and enhance the antitumor activity of 5-fluorouracil (5-FU). (nih.gov)
  • Neu-Laxova syndrome is characterized by severe intrauterine growth deficiency, microcephaly, congenital bilateral cataracts, characteristic dysmorphic features, limb anomalies, and collodion-like ichthyosis. (nih.gov)
  • These patients suffered from severe neurological symptoms and were identified because of low plasma and CSF serine concentrations upon routine amino acid analysis. (mhmedical.com)
  • Increased serine biosynthesis occurs in several cancers and supports tumor growth. (nih.gov)
  • Catalyzes the last step in the biosynthesis of serine from carbohydrates. (nih.gov)
  • It is appropriate to evaluate newborn sibs and apparently asymptomatic older and younger sibs of a proband to identify as early as possible those who would benefit from prompt initiation of L-serine treatment. (nih.gov)
  • Improvements in drug detection between the two PT events in each year demonstrated the benefit of PT schemes in identifying and addressing potential deficiencies in laboratory systems. (cdc.gov)
  • Collectively, our results suggest that both endogenous and exogenous sources of serine contribute to colorectal cancer growth and resistance to 5-FU. (nih.gov)
  • Serine plays an important role in the catalytic function of many enzymes. (iiab.me)
  • Gastrointestinal absorption of cobalamin depends on the presence of sufficient intrinsic factor, and lack of intrinisic factor results in cobalamin deficiency. (nih.gov)
  • Specifically, vitamin B 12 deficiency allowed to progress over 3 months may produce permanent degenerative lesions of the spinal cord - as observed when vitamin B 9 therapy is used as the only hematopoietic agent. (nih.gov)
  • Adult-onset serine deficiency is characterized by progressive axonal polyneuropathy with ataxia and possible cognitive impairment. (nih.gov)