پیرووات دهیدروژناز (لیپوآمید) آلفا ۱

PDHA1
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	1NI4, 2OZL, 3EXE, 3EXF, 3EXG, 3EXH, 3EXI
معین‌کننده‌ها
نام‌های دیگر	PDHA1, PDHA, PDHCE1A, PHE1A, PDHAD, Pyruvate dehydrogenase (lipoamide) alpha 1, pyruvate dehydrogenase alpha 1, pyruvate dehydrogenase E1 alpha 1 subunit, pyruvate dehydrogenase E1 subunit alpha 1
شناسه‌های بیرونی	OMIM: 300502 MGI: 97532 HomoloGene: 121491 GeneCards: PDHA1
موقعیت ژن (انسان)
کروموزوم	کروموزوم X (انسان)
پایان	19,361,718 bp
موقعیت ژن (موش)
کروموزوم	کروموزوم X (موش)
پایان	158,921,409 bp
الگوی گسترش RNA
	; ;
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• pyruvate dehydrogenase activity; • oxidoreductase activity; • pyruvate dehydrogenase (acetyl-transferring) activity; • oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor; • pyruvate dehydrogenase (NAD+) activity; • GO:0001948، GO:0016582 پیوند پروتئینی;
ترکیبات سلولی	• intracellular membrane-bounded organelle; • myelin sheath; • pyruvate dehydrogenase complex; • mitochondrial matrix; • هسته یاخته; • هستک; • میتوکندری;
فرایند زیستی	• mitochondrial acetyl-CoA biosynthetic process from pyruvate; • چرخه اسید سیتریک; • regulation of acetyl-CoA biosynthetic process from pyruvate; • pyruvate metabolic process; • glucose metabolic process; • دگرگشت; • acetyl-CoA biosynthetic process from pyruvate; • cellular nitrogen compound metabolic process; • سوخت‌وساز کربوهیدرات;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	5160
	18597
	ENSG00000131828
	ENSMUSG00000031299
	P08559; Q5JPT9
	P35486
	NM_001173454، NM_001173455، NM_001173456، XM_017029574 NM_000284، NM_001173454، NM_001173455، NM_001173456، XM_017029574
	NM_008810
	NP_001166925، NP_001166926، NP_001166927، XP_016885063 NP_000275، NP_001166925، NP_001166926، NP_001166927، XP_016885063
	NP_032836
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

پیرووات دهیدروژناز E1 زیرواحد ساختمانی آلفا، فرم غیرجنسی، میتوکندریایی (انگلیسی: Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial) یک آنزیم است که در انسان توسط ژن «PDHA1» کُدگذاری می‌شود. کمپلکس پیرووات دهیدروژناز، یک ترکیب آنزیمی ماتریکس میتوکندری و کدشونده در هسته است که ارتباط اولیه مابین گلیکولیز و چرخه اسید سیتریک را، از طریق تبدیل برگشت‌ناپذیر پیروویک اسید به استیل-کوآ فراهم می‌کند.

زیرواحد E1-آلفا، حاوی جایگاه فعالِ E1 است و نقش مهمی در عملکردِ کمپلکس پیرووات دهیدروژناز ایفا می‌کند.^[۵]

اهمیت بالینی ویرایش

جهش در ژن «PDHA1» سبب بروز یکی از انواع کمبود پیرووات دهیدروژناز می‌گردد. طیف این جهش ژنی از یک جهش بدمعنی (تغییرِ تنها یک نوکلئوتید) تا حذف‌های گسترده چندین جفت نوکلئوتید متغیر است.^[۶]^[۷]^[۸]

منابع ویرایش

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCh38: Ensembl release 89: ENSG00000131828 - Ensembl, May 2017
↑ ^۲٫۰ ^۲٫۱ ^۲٫۲ GRCm38: Ensembl release 89: ENSMUSG00000031299 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: PDHA1 pyruvate dehydrogenase (lipoamide) alpha 1".
↑ Giribaldi G, Doria-Lamba L, Biancheri R, Severino M, Rossi A, Santorelli FM, Schiaffino C, Caruso U, Piemonte F, Bruno C (May 2012). "Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility". Developmental Medicine and Child Neurology. 54 (5): 472–6. doi:10.1111/j.1469-8749.2011.04151.x. PMID 22142326.
↑ Magner M, Vinšová K, Tesařová M, Hájková Z, Hansíková H, Wenchich L, Ješina P, Smolka V, Adam T, Vaněčková M, Zeman J, Honzík T (2011). "Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene". Prague Medical Report. 112 (1): 18–28. PMID 21470495.
↑ Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M (Dec 2011). "Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein". Molecular Genetics and Metabolism. 104 (4): 507–16. doi:10.1016/j.ymgme.2011.08.008. PMID 21914562.

مشارکت‌کنندگان ویکی‌پدیا. «Pyruvate dehydrogenase (lipoamide) alpha 1». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۲۶ اکتبر ۲۰۱۸.

بیشتر بخوانید ویرایش

Dahl HH, Brown GK, Brown RM, Hansen LL, Kerr DS, Wexler ID, Patel MS, De Meirleir L, Lissens W, Chun K (1993). "Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene". Human Mutation. 1 (2): 97–102. doi:10.1002/humu.1380010203. PMID 1301207.
Brown GK, Otero LJ, LeGris M, Brown RM (Nov 1994). "Pyruvate dehydrogenase deficiency". Journal of Medical Genetics. 31 (11): 875–9. doi:10.1136/jmg.31.11.875. PMC 1016663. PMID 7853374.
Sugden MC, Holness MJ (May 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855–62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.
Dahl HH, Hansen LL, Brown RM, Danks DM, Rogers JG, Brown GK (1993). "X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation". Journal of Inherited Metabolic Disease. 15 (6): 835–47. doi:10.1007/BF01800219. PMID 1293379.
Ito M, Huq AH, Naito E, Saijo T, Takeda E, Kuroda Y (1993). "Mutation of E1 alpha gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein". Journal of Inherited Metabolic Disease. 15 (6): 848–56. doi:10.1007/BF01800220. PMID 1338114.
De Meirleir L, Lissens W, Vamos E, Liebaers I (Mar 1992). "Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the E1 alpha subunit". Human Genetics. 88 (6): 649–52. doi:10.1007/BF02265291. PMID 1551669.
Hansen LL, Brown GK, Kirby DM, Dahl HH (1991). "Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency". Journal of Inherited Metabolic Disease. 14 (2): 140–51. doi:10.1007/BF01800586. PMID 1909401.
Koike K, Urata Y, Matsuo S, Koike M (Sep 1990). "Characterization and nucleotide sequence of the gene encoding the human pyruvate dehydrogenase alpha-subunit". Gene. 93 (2): 307–11. doi:10.1016/0378-1119(90)90241-I. PMID 2227443.
Endo H, Hasegawa K, Narisawa K, Tada K, Kagawa Y, Ohta S (Mar 1989). "Defective gene in lactic acidosis: abnormal pyruvate dehydrogenase E1 alpha-subunit caused by a frame shift". American Journal of Human Genetics. 44 (3): 358–64. PMC 1715432. PMID 2537010.
Brown RM, Dahl HH, Brown GK (Feb 1989). "X-chromosome localization of the functional gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex". Genomics. 4 (2): 174–81. doi:10.1016/0888-7543(89)90297-8. PMID 2737678.
Maragos C, Hutchison WM, Hayasaka K, Brown GK, Dahl HH (Jul 1989). "Structural organization of the gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex". The Journal of Biological Chemistry. 264 (21): 12294–8. PMID 2745444.
Ho L, Wexler ID, Liu TC, Thekkumkara TJ, Patel MS (Jul 1989). "Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit". Proceedings of the National Academy of Sciences of the United States of America. 86 (14): 5330–4. doi:10.1073/pnas.86.14.5330. PMC 297615. PMID 2748588.
De Meirleir L, MacKay N, Lam Hon Wah AM, Robinson BH (Feb 1988). "Isolation of a full-length complementary DNA coding for human E1 alpha subunit of the pyruvate dehydrogenase complex". The Journal of Biological Chemistry. 263 (4): 1991–5. PMID 2828359.
Dahl HH, Hunt SM, Hutchison WM, Brown GK (May 1987). "The human pyruvate dehydrogenase complex. Isolation of cDNA clones for the E1 alpha subunit, sequence analysis, and characterization of the mRNA". The Journal of Biological Chemistry. 262 (15): 7398–403. PMID 3034892.
Koike K, Ohta S, Urata Y, Kagawa Y, Koike M (Jan 1988). "Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase". Proceedings of the National Academy of Sciences of the United States of America. 85 (1): 41–5. doi:10.1073/pnas.85.1.41. PMC 279477. PMID 3422424.
Hansen LL, Horn N, Dahl HH, Kruse TA (Jun 1994). "Pyruvate dehydrogenase deficiency caused by a 33 base pair duplication in the PDH E1 alpha subunit". Human Molecular Genetics. 3 (6): 1021–2. doi:10.1093/hmg/3.6.1021. PMID 7545958.
Takakubo F, Cartwright P, Hoogenraad N, Thorburn DR, Collins F, Lithgow T, Dahl HH (Oct 1995). "An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein". American Journal of Human Genetics. 57 (4): 772–80. PMC 1801496. PMID 7573035.
Hemalatha SG, Kerr DS, Wexler ID, Lusk MM, Kaung M, Du Y, Kolli M, Schelper RL, Patel MS (Feb 1995). "Pyruvate dehydrogenase complex deficiency due to a point mutation (P188L) within the thiamine pyrophosphate binding loop of the E1 alpha subunit". Human Molecular Genetics. 4 (2): 315–8. doi:10.1093/hmg/4.2.315. PMID 7757088.

[refGRCh38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCh38: Ensembl release 89: ENSG00000131828 - Ensembl, May 2017

[refGRCm38Ensembl-2] ۲٫۰ ^۲٫۱ ^۲٫۲ GRCm38: Ensembl release 89: ENSMUSG00000031299 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: PDHA1 pyruvate dehydrogenase (lipoamide) alpha 1".

[6] Giribaldi G, Doria-Lamba L, Biancheri R, Severino M, Rossi A, Santorelli FM, Schiaffino C, Caruso U, Piemonte F, Bruno C (May 2012). "Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility". Developmental Medicine and Child Neurology. 54 (5): 472–6. doi:10.1111/j.1469-8749.2011.04151.x. PMID 22142326.

[7] Magner M, Vinšová K, Tesařová M, Hájková Z, Hansíková H, Wenchich L, Ješina P, Smolka V, Adam T, Vaněčková M, Zeman J, Honzík T (2011). "Two patients with clinically distinct manifestation of pyruvate dehydrogenase deficiency due to mutations in PDHA1 gene". Prague Medical Report. 112 (1): 18–28. PMID 21470495.

[8] Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M (Dec 2011). "Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein". Molecular Genetics and Metabolism. 104 (4): 507–16. doi:10.1016/j.ymgme.2011.08.008. PMID 21914562.

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