Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Non-Ketotic Hyperglycinemia
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2013-08-19
Last Updated: 2022-10-24
Non Ketotic Hyperglycinemeia (Glycine encephalopathy; Glycine cleavage system deficiency; NKH) is caused by mutations in several genes in the mitochondrial glycine cleavage system. These include the genes encoding P protein (GLDC), T protein (GCST), and, in one case, the H protein (GCSH). Most patients with GCE (Glycine Encephalopathy, or NKH) have a defect in the GLDC gene.The enzyme system for cleavage of glycine (glycine cleavage system), which is confined to the mitochondria, is composed of 4 protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). NKH is characterized by accumulation of glycine in plasma, spinal fluid and urine. Symptoms include seizures, respiratory distress, mental retardation, chorea, visual impairment and hydrocephalus.
References
Non-Ketotic Hyperglycinemia References
[Uniprot: P48728](http://www.uniprot.org/uniprot/P48728)
[OMIM: Entry 605899](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605899)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.76 Heilbronn: SPS Verlagsgesellschaft
Applegarth DA, Toone JR: Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis. Mol Genet Metab. 2001 Sep-Oct;74(1-2):139-46. doi: 10.1006/mgme.2001.3224.
Pubmed: 11592811
Cole DE, Meek DC: Juvenile non-ketotic hyperglycinaemia in three siblings. J Inherit Metab Dis. 1985;8 Suppl 2:123-4.
Pubmed: 3930859
Flannery DB, Pellock J, Bousounis D, Hunt P, Nance C, Wolf B: Nonketotic hyperglycinemia in two retarded adults: a mild form of infantile nonketotic hyperglycinemia. Neurology. 1983 Aug;33(8):1064-6.
Pubmed: 6683804
Hayasaka K, Tada K, Kikuchi G, Winter S, Nyhan WL: Nonketotic hyperglycinemia: two patients with primary defects of P-protein and T-protein, respectively, in the glycine cleavage system. Pediatr Res. 1983 Dec;17(12):967-70.
Pubmed: 6336599
Hiraga K, Koyata H, Sakakibara T, Ishiguro Y, Matsui C: Non-ketotic hyperglycinemia: an aim of the second generation of studies on pathogenesis. Mol Biol Med. 1991 Feb;8(1):65-79.
Pubmed: 1943691
Glycine and Serine Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Hsu YP, Weyler W, Chen S, Sims KB, Rinehart WB, Utterback MC, Powell JF, Breakefield XO: Structural features of human monoamine oxidase A elucidated from cDNA and peptide sequences. J Neurochem. 1988 Oct;51(4):1321-4. doi: 10.1111/j.1471-4159.1988.tb03105.x.
Pubmed: 3418353
Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC: cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4934-8. doi: 10.1073/pnas.85.13.4934.
Pubmed: 3387449
Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I, et al.: Structure of the human gene for monoamine oxidase type A. Nucleic Acids Res. 1991 Aug 25;19(16):4537-41. doi: 10.1093/nar/19.16.4537.
Pubmed: 1886775
Novoradovsky A, Tsai SJ, Goldfarb L, Peterson R, Long JC, Goldman D: Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles. Alcohol Clin Exp Res. 1995 Oct;19(5):1105-10. doi: 10.1111/j.1530-0277.1995.tb01587.x.
Pubmed: 8561277
Braun T, Bober E, Singh S, Agarwal DP, Goedde HW: Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase. FEBS Lett. 1987 May 11;215(2):233-6. doi: 10.1016/0014-5793(87)80152-7.
Pubmed: 3582651
Braun T, Bober E, Singh S, Agarwal DP, Goedde HW: Isolation and sequence analysis of a full length cDNA clone coding for human mitochondrial aldehyde dehydrogenase. Nucleic Acids Res. 1987 Apr 10;15(7):3179. doi: 10.1093/nar/15.7.3179.
Pubmed: 3562250
Edgar AJ, Polak JM: Molecular cloning of the human and murine 2-amino-3-ketobutyrate coenzyme A ligase cDNAs. Eur J Biochem. 2000 Mar;267(6):1805-12. doi: 10.1046/j.1432-1327.2000.01175.x.
Pubmed: 10712613
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. doi: 10.1038/990031.
Pubmed: 10591208
Binzak BA, Vockley JG, Jenkins RB, Vockley J: Structure and analysis of the human dimethylglycine dehydrogenase gene. Mol Genet Metab. 2000 Mar;69(3):181-7. doi: 10.1006/mgme.2000.2980.
Pubmed: 10767172
Binzak BA, Wevers RA, Moolenaar SH, Lee YM, Hwu WL, Poggi-Bach J, Engelke UF, Hoard HM, Vockley JG, Vockley J: Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency. Am J Hum Genet. 2001 Apr;68(4):839-47. doi: 10.1086/319520. Epub 2001 Feb 28.
Pubmed: 11231903
Eschenbrenner M, Jorns MS: Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia. Genomics. 1999 Aug 1;59(3):300-8. doi: 10.1006/geno.1999.5886.
Pubmed: 10444331
Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. doi: 10.1038/nature02465.
Pubmed: 15164053
Kure S, Narisawa K, Tada K: Structural and expression analyses of normal and mutant mRNA encoding glycine decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia. Biochem Biophys Res Commun. 1991 Feb 14;174(3):1176-82. doi: 10.1016/0006-291x(91)91545-n.
Pubmed: 1996985
Kume A, Koyata H, Sakakibara T, Ishiguro Y, Kure S, Hiraga K: The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures. J Biol Chem. 1991 Feb 15;266(5):3323-9.
Pubmed: 1993704
Hayasaka K, Nanao K, Takada G, Okamura-Ikeda K, Motokawa Y: Isolation and sequence determination of cDNA encoding human T-protein of the glycine cleavage system. Biochem Biophys Res Commun. 1993 Apr 30;192(2):766-71. doi: 10.1006/bbrc.1993.1480.
Pubmed: 7916605
Nanao K, Takada G, Takahashi E, Seki N, Komatsu Y, Okamura-Ikeda K, Motokawa Y, Hayasaka K: Structure and chromosomal localization of the aminomethyltransferase gene (AMT) Genomics. 1994 Jan 1;19(1):27-30.
Pubmed: 8188235
Yang X, Wang Z, Li X, Liu B, Liu M, Liu L, Chen S, Ren M, Wang Y, Yu M, Wang B, Zou J, Zhu WG, Yin Y, Gu W, Luo J: SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation. Cancer Res. 2018 Jan 15;78(2):372-386. doi: 10.1158/0008-5472.CAN-17-1912. Epub 2017 Nov 27.
Pubmed: 29180469
Minton DR, Nam M, McLaughlin DJ, Shin J, Bayraktar EC, Alvarez SW, Sviderskiy VO, Papagiannakopoulos T, Sabatini DM, Birsoy K, Possemato R: Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs. Mol Cell. 2018 Feb 15;69(4):610-621.e5. doi: 10.1016/j.molcel.2018.01.024.
Pubmed: 29452640
Feigenbaum AS, Robinson BH: The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics. 1993 Aug;17(2):376-81. doi: 10.1006/geno.1993.1335.
Pubmed: 8406489
Otulakowski G, Robinson BH: Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases. J Biol Chem. 1987 Dec 25;262(36):17313-8.
Pubmed: 3693355
Pons G, Raefsky-Estrin C, Carothers DJ, Pepin RA, Javed AA, Jesse BW, Ganapathi MK, Samols D, Patel MS: Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1422-6. doi: 10.1073/pnas.85.5.1422.
Pubmed: 3278312
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings