Izvorni kôd stranice GALT

{{Infokutija gen}}
{{Infokutija protein
| Symbol = GalP_UDP_transf
|Ime = [[N-terminal]]ni domen galaktoza-1-fosfat uridil-transferaze 
| image =
| width = 
| caption = 
| Pfam = PF01087
| Pfam_clan = CL0265 
| InterPro = 
| SMART = 
| PROSITE = PDOC00108
| MEROPS = 
| SCOP = 1hxp
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
{{Infokutija protein
| Symbol = GalP_UDP_tr_C
| Ime = [[C-terminal]]ni domen galaktoza-1-fosfat uridil-transferaze
| image = PDB 1gup EBI.jpg
| width = 
| caption = Struktura nukleotidiltransferaze kompleksirane sa [[UDP]]-[[galaktoza|galaktozom]]
| Pfam = PF02744
| Pfam_clan = CL0265 
| InterPro = IPR005850
| SMART = 
| PROSITE = PDOC00108
| MEROPS = 
| SCOP = 1hxp
| TCDB = 
| OPM family = 
| OPM protein = 
| CAZy = 
| CDD = 
}}
'''Galaktoza-1-fosfat uridililtransferaza''' – '''GALT''' ili '''G1PUT''' –  je [[enzim]] ([[EC broj|EC 2.7.7.12]]) odgovoran za pretvaranje unesene [[galaktoza|galaktoze]] u [[glukoza|glukozu]].<ref name="entrez">{{cite web | title = Entrez Gene: GALT galactose-1-phosphate uridylyltransferase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2592}}</ref>

Galaktoza-1-fosfat uridilililtransferaza (GALT) katalizira drugi korak [[Leloir]] puta [[metabolizam|metabolizma]] [[galaktoza|galaktoze]]:
: [[UDP-glukoza]] + [[galaktoza 1-fosfat]]<math>\rightleftharpoons</math> [[glukoza 1-fosfat]] + [[UDP-galaktoza]]
:[[ekspresija gena|Ekspresija]] GALT -a kontrolira se djelovanjem gena [[FOXO3]]. Nedostatak ovog enzima dovodi do klasične [[galaktozemija|galaktozemije]] kod ljudi i može biti smrtonosan u dobi novorođenčadi ako se [[laktoza]] ne ukloni iz prehrane. Patofiziologija galaktozemije nije jasno definirana.<ref name="entrez"/>
<gallery>
 DGalactose Fischer.svg|[[Galaktoza]]
 D-glucose chain (Fischer).svg|[[Glukoza]]
</gallery>
==Aminokiselinska sekvenca==
Dužina [[polipeptid]]nog lanca je 379 [[aminokiselina]], а [[molekularna masa|molekulska težina]]  43.363 [[dalton (jedinica)|Da]].<ref name="UniProt">{{cite web|url=http://www.uniprot.org/uniprot/P07902#sequences |title=UniProt, P07902 |access-date=8. 9. 2021}}</ref>
{{legenda aminokiselina}}
<table  style="font-family:monospace;">
<tr style="text-align:right;"><th>10</th><th></th><th>20</th><th></th><th>30</th><th></th><th>40</th><th></th><th>50</th></tr>
<tr style="background-color: #eee;"><td>MSRSGTDPQQ</td><td style="background-color: #f9f9f9;"></td><td>RQQASEADAA</td><td style="background-color: #f9f9f9;"></td><td>AATFRANDHQ</td><td style="background-color: #f9f9f9;"></td><td>HIRYNPLQDE</td><td style="background-color: #f9f9f9;"></td><td>WVLVSAHRMK</td></tr>
<tr style="background-color: #eee;"><td>RPWQGQVEPQ</td><td style="background-color: #f9f9f9;"></td><td>LLKTVPRHDP</td><td style="background-color: #f9f9f9;"></td><td>LNPLCPGAIR</td><td style="background-color: #f9f9f9;"></td><td>ANGEVNPQYD</td><td style="background-color: #f9f9f9;"></td><td>STFLFDNDFP</td></tr>
<tr style="background-color: #eee;"><td>ALQPDAPSPG</td><td style="background-color: #f9f9f9;"></td><td>PSDHPLFQAK</td><td style="background-color: #f9f9f9;"></td><td>SARGVCKVMC</td><td style="background-color: #f9f9f9;"></td><td>FHPWSDVTLP</td><td style="background-color: #f9f9f9;"></td><td>LMSVPEIRAV</td></tr>
<tr style="background-color: #eee;"><td>VDAWASVTEE</td><td style="background-color: #f9f9f9;"></td><td>LGAQYPWVQI</td><td style="background-color: #f9f9f9;"></td><td>FENKGAMMGC</td><td style="background-color: #f9f9f9;"></td><td>SNPHPHCQVW</td><td style="background-color: #f9f9f9;"></td><td>ASSFLPDIAQ</td></tr>
<tr style="background-color: #eee;"><td>REERSQQAYK</td><td style="background-color: #f9f9f9;"></td><td>SQHGEPLLME</td><td style="background-color: #f9f9f9;"></td><td>YSRQELLRKE</td><td style="background-color: #f9f9f9;"></td><td>RLVLTSEHWL</td><td style="background-color: #f9f9f9;"></td><td>VLVPFWATWP</td></tr>
<tr style="background-color: #eee;"><td>YQTLLLPRRH</td><td style="background-color: #f9f9f9;"></td><td>VRRLPELTPA</td><td style="background-color: #f9f9f9;"></td><td>ERDDLASIMK</td><td style="background-color: #f9f9f9;"></td><td>KLLTKYDNLF</td><td style="background-color: #f9f9f9;"></td><td>ETSFPYSMGW</td></tr>
<tr style="background-color: #eee;"><td>HGAPTGSEAG</td><td style="background-color: #f9f9f9;"></td><td>ANWNHWQLHA</td><td style="background-color: #f9f9f9;"></td><td>HYYPPLLRSA</td><td style="background-color: #f9f9f9;"></td><td>TVRKFMVGYE</td><td style="background-color: #f9f9f9;"></td><td>MLAQAQRDLT</td></tr>
<tr style="background-color: #eee;"><td>PEQAAERLRA</td><td style="background-color: #f9f9f9;"></td><td>LPEVHYHLGQ</td><td style="background-color: #f9f9f9;"></td><td>KDRETATIA</td></tr>
</table>

== Strukturne studije ==
Trodimenzijsku strukturu pri rezoluciji 180 [[pikometar|pm]] ([[kristalografija rendgenskih zraka]]) GALT-a odredili su Wedekind, Frey i Rayment, a njihovom strukturnom analizom utvrđeno je da su ključne [[aminokiseline]] bitne za funkciju GALT. Među njima su [[leucin|Leu4]], [[fenilalanin|Phe75]], [[asparagin|Asn77]], [[asparagin|Asp78]], [[fenilalanin|Phe79]] i [[valin|Val108]], koji su u skladu s ostacima koji su uključeni, kako u eksperimente s [[tačkasta mutacija|tačkastom mutacijom]], tako i u klinički skrining koji imaju ulogu u ljudskoj galaktozemiji.<ref name="mutations">{{cite journal | vauthors = Seyrantepe V, Ozguc M, Coskun T, Ozalp I, Reichardt JK | title = Identification of mutations in the galactose-1-phosphate uridyltransferase (GALT) gene in 16 Turkish patients with galactosemia, including a novel mutation of F294Y. Mutation in brief no. 235. Online | journal = Human Mutation | volume = 13 | issue = 4 | pages = 339 | year = 1999 | pmid = 10220154 | doi = 10.1002/(SICI)1098-1004(1999)13:4<339::AID-HUMU18>3.0.CO;2-S | doi-access = free }}</ref>

== Mehanizam ==
GALT katalizira drugu reakciju Leloirovog puta metabolizma galaktoze, [[hemijska kinetika|kinetikom]] modela ping pong bi-bi, mehanizmom [[dvostruki pomak]].<ref name="test">{{cite journal | vauthors = Wong LJ, Frey PA | title = Galactose-1-phosphate uridylyltransferase: rate studies confirming a uridylyl-enzyme intermediate on the catalytic pathway | journal = Biochemistry | volume = 13 | issue = 19 | pages = 3889–94 | date = septembar 1974 | pmid = 4606575 | doi = 10.1021/bi00716a011 }}</ref>  To znači da se neto reakcija sastoji od dva reaktanta i dva produkta (vidi gore navedenu reakciju), a odvija se prema sljedećem mehanizmu: enzim reagira s jednim [[supstrat (biohemija)|supstratom]], stvarajući jedan [[proizvod (biohemija)|proizvod]] i modificirani enzim, koji nastavlja reagirati s drugim supstrata za stvaranje drugog proizvoda, uz regeneraciju izvornog [[enzim]]a.<ref name="bibi">{{Cite web |url=http://www.mondofacto.com/facts/dictionary?double+displacement+mechanism |title=Archived copy |access-date=19. 5. 2010 |archive-url=https://web.archive.org/web/20160303204044/http://www.mondofacto.com/facts/dictionary?double+displacement+mechanism |archive-date=3. 3. 2016 |url-status=dead }}</ref>  U slučaju GALT-a, ostatak His166 djeluje kao moćan [[nukleofil]] kako bi olakšao prijenos [[nukleotid]]a između UDP-heksoza i heksoza-1-fosfata.<ref name="structure">{{cite journal | vauthors = Wedekind JE, Frey PA, Rayment I | title = Three-dimensional structure of galactose-1-phosphate uridylyltransferase from Escherichia coli at 1.8 A resolution | journal = Biochemistry | volume = 34 | issue = 35 | pages = 11049–61 | date = septembar 1995 | pmid = 7669762 | doi = 10.1021/bi00035a010 }}</ref>

#UDP-glukoza + E-His<math>\rightleftharpoons</math>glukoza-1-fosfat + E-His-UMP
#Galaktoza-1-fosfat + E-His-UMP<math>\rightleftharpoons</math>UDP-galaktoza + E-His<ref name="structure"/>
[[slika:GALT.JPG|left|thumb| Dvostepeno djelovanje galaktoza-1-fosfat uridililtransferaze. Slika prema:<ref name="pic">{{Cite web |url=http://web.virginia.edu/Heidi/chapter19/chp19frameset.htm |title=Archived copy |access-date=19. 5. 2010 |archive-url=https://web.archive.org/web/20081204112912/http://www.web.virginia.edu/Heidi/chapter19/chp19frameset.htm |archive-date=4. 12. 2008 |url-status=dead }}</ref>]]

== Klinički značaj ==
Nedostatak GALT uzrokuje [[galaktozemija|klasičnu galaktozemiju]]. [[Galaktozemija]] je autosomno recesivni [[nasljedni poremećaj]] koji se može otkriti kod novorođenčadi i u djetinjstvu.<ref name="Frido">{{cite journal | vauthors = Fridovich-Keil JL | title = Galactosemia: the good, the bad, and the unknown | journal = Journal of Cellular Physiology | volume = 209 | issue = 3 | pages = 701–5 | date = decembar 2006 | pmid = 17001680 | doi = 10.1002/jcp.20820 | s2cid = 32233614 }}</ref>  Javlja se otprilike 1/40.000 – 60.000 živorođene djece. [[Klasična galaktozemija]] (G/G) uzrokovana je nedostatkom GALT aktivnosti, dok su češće kliničke manifestacije, [[Nedostatak galaktoza-1-fosfat uridililtransferaze Duarte (D/D) i Duarte/klasična varijanta (D/G)]] uzrokovane su slabljenjem aktivnosti GALT-a.<ref name="Elsas 1995">{{cite journal | vauthors = Elsas LJ, Langley S, Paulk EM, Hjelm LN, Dembure PP | title = A molecular approach to galactosemia | journal = European Journal of Pediatrics | volume = 154 | issue = 7 Suppl 2 | pages = S21-7 | year = 1995 | pmid = 7671959 | doi = 10.1007/BF02143798 | s2cid = 11937698 }}</ref> Simptomi uključuju otkazivanje [[jajnik]]a, [[razvojni poremećaj koordinacije]] (poteškoće u korektnom i konzistentnom [[govor]]u),<ref name="apraxia">{{cite web |url=http://www.nidcd.nih.gov/health/voice/apraxia.htm |title=Archived copy |access-date=19. 5. 2010 |url-status=dead |archive-url=https://web.archive.org/web/20060228083020/http://www.nidcd.nih.gov/health/voice/apraxia.htm |archive-date=28. 2. 2006 }}</ref> i [[nerv]]ne nedostatke.<ref name="Elsas 1995"/> Jedna [[mutacija]] u bilo kojem od nekoliko parova baza može dovesti do nedostatka aktivnosti GALT-a.<ref name="Dob">{{cite journal | vauthors = Dobrowolski SF, Banas RA, Suzow JG, Berkley M, Naylor EW | title = Analysis of common mutations in the galactose-1-phosphate uridyl transferase gene: new assays to increase the sensitivity and specificity of newborn screening for galactosemia | journal = The Journal of Molecular Diagnostics | volume = 5 | issue = 1 | pages = 42–7 | date = februar 2003 | pmid = 12552079 | pmc = 1907369 | doi = 10.1016/S1525-1578(10)60450-3 }}</ref> Naprimjer, jedna [[mutacija]] iz A u G u [[egzon]]u 6 gena GALT mijenja Glu188 u [[arginin]], a mutacija iz A u G u egzonu 10 pretvara Asn314 u [[asparaginska kiselina|aspartat]].<ref name = "Elsas 1995"/> Ove dvije mutacije također dodaju nova rezna mjesta [[restrikcijski enzim|restrikcijskih enzima]], koja omogućuju detekciju i opsežni skrining populacije pomoću [[PCR]]-a ([[PCR|lančana reakcija polimeraze]]).<ref name = "Elsas 1995 "/> Skriningom je uglavnom eliminirana neonatusna smrt uzrokovana G /G galaktozemijom, ali je bolest, zbog uloge GALT-a u biohemijskom [[metabolizam|metabolizmu]] unesene [[galaktoza|galaktoze]] (koja je otrovna pri akumulaciji) energetski korisna [[glukoza]], svakako može biti smrtonosna.<ref name="Frido" /><ref name="lethal">{{cite journal | vauthors = Lai K, Elsas LJ, Wierenga KJ | title = Galactose toxicity in animals | journal = IUBMB Life | volume = 61 | issue = 11 | pages = 1063–74 | date = novembar 2009 | pmid = 19859980 | pmc = 2788023 | doi = 10.1002/iub.262 }}</ref> Međutim, oboljeli od galaktozemije mogu živjeti relativno normalnim životom izbjegavajući mliječne proizvode i bilo što drugo što sadrži galaktozu (jer se ne može metabolizirati), ali još uvijek postoji potencijal za probleme u neurološkom razvoju ili druge komplikacije, čak i kod onih koji izbjegavaju galaktozu.<ref name="med">{{Cite web |url=http://www.umm.edu/ency/article/000366trt.htm |title=Arhivirana kopija |access-date=8. 9. 2021 |archive-date=29. 5. 2013 |archive-url=https://web.archive.org/web/20130529140128/http://www.umm.edu/ency/article/000366trt.htm |url-status=dead }}</ref>

==Baza podataka bolesti==
[http://www.arup.utah.edu/database/GALT/GALT_display.php Galactosemia (GALT) Mutation Database]{{clear}}

== Reference ==
{{reflist|30em}}

== Dopunska literatura ==
{{refbegin|30em}}
* {{cite journal | vauthors = Reichardt JK | title = Genetic basis of galactosemia | journal = Human Mutation | volume = 1 | issue = 3 | pages = 190–6 | year = 1993 | pmid = 1301925 | doi = 10.1002/humu.1380010303 | s2cid = 504197 }}
* {{cite journal | vauthors = Tyfield L, Reichardt J, Fridovich-Keil J, Croke DT, Elsas LJ, Strobl W, Kozak L, Coskun T, Novelli G, Okano Y, Zekanowski C, Shin Y, Boleda MD | title = Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene | journal = Human Mutation | volume = 13 | issue = 6 | pages = 417–30 | year = 1999 | pmid = 10408771 | doi = 10.1002/(SICI)1098-1004(1999)13:6<417::AID-HUMU1>3.0.CO;2-0 }}
* {{cite journal | vauthors = Reichardt JK, Belmont JW, Levy HL, Woo SL | title = Characterization of two missense mutations in human galactose-1-phosphate uridyltransferase: different molecular mechanisms for galactosemia | journal = Genomics | volume = 12 | issue = 3 | pages = 596–600 | date = mart 1992 | pmid = 1373122 | doi = 10.1016/0888-7543(92)90453-Y }}
* {{cite journal | vauthors = Leslie ND, Immerman EB, Flach JE, Florez M, Fridovich-Keil JL, Elsas LJ | title = The human galactose-1-phosphate uridyltransferase gene | journal = Genomics | volume = 14 | issue = 2 | pages = 474–80 | date = oktobar 1992 | pmid = 1427861 | doi = 10.1016/S0888-7543(05)80244-7 }}
* {{cite journal | vauthors = Reichardt JK, Levy HL, Woo SL | title = Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase | journal = Biochemistry | volume = 31 | issue = 24 | pages = 5430–3 | date = juni 1992 | pmid = 1610789 | doi = 10.1021/bi00139a002 }}
* {{cite journal | vauthors = Reichardt JK, Packman S, Woo SL | title = Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase | journal = American Journal of Human Genetics | volume = 49 | issue = 4 | pages = 860–7 | date = oktobar 1991 | pmid = 1897530 | pmc = 1683190 }}
* {{cite journal | vauthors = Reichardt JK, Woo SL | title = Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 7 | pages = 2633–7 | date = april 1991 | pmid = 2011574 | pmc = 51292 | doi = 10.1073/pnas.88.7.2633 | bibcode = 1991PNAS...88.2633R | doi-access = free }}
* {{cite journal | vauthors = Flach JE, Reichardt JK, Elsas LJ | title = Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase | journal = Molecular Biology & Medicine | volume = 7 | issue = 4 | pages = 365–9 | date = august 1990 | pmid = 2233247 }}
* {{cite journal | vauthors = Reichardt JK, Berg P | title = Cloning and characterization of a cDNA encoding human galactose-1-phosphate uridyl transferase | journal = Molecular Biology & Medicine | volume = 5 | issue = 2 | pages = 107–22 | date = april 1988 | pmid = 2840550 }}
* {{cite journal | vauthors = Bergren WG, Donnell GN | title = A new variant of galactose-1-phosphate uridyltransferase in man: the Los Angeles variant | journal = Annals of Human Genetics | volume = 37 | issue = 1 | pages = 1–8 | date = juli 1973 | pmid = 4759900 | doi = 10.1111/j.1469-1809.1973.tb01808.x | s2cid = 22699183 }}
* {{cite journal | vauthors = Shih LY, Suslak L, Rosin I, Searle BM, Desposito F | title = Gene dosage studies supporting localization of the structural gene for galactose-1-phosphate uridyl transferase (GALT) to band p13 of chromosome 9 | journal = American Journal of Medical Genetics | volume = 19 | issue = 3 | pages = 539–43 | date = novembar 1984 | pmid = 6095663 | doi = 10.1002/ajmg.1320190316 }}
* {{cite journal | vauthors = Ashino J, Okano Y, Suyama I, Yamazaki T, Yoshino M, Furuyama J, Lin HC, Reichardt JK, Isshiki G | title = Molecular characterization of galactosemia (type 1) mutations in Japanese | journal = Human Mutation | volume = 6 | issue = 1 | pages = 36–43 | year = 1995 | pmid = 7550229 | doi = 10.1002/humu.1380060108 | s2cid = 23500152 }}
* {{cite journal | vauthors = Elsas LJ, Langley S, Paulk EM, Hjelm LN, Dembure PP | title = A molecular approach to galactosemia | journal = European Journal of Pediatrics | volume = 154 | issue = 7 Suppl 2 | pages = S21-7 | year = 1995 | pmid = 7671959 | doi = 10.1007/BF02143798 | s2cid = 11937698 }}
* {{cite journal | vauthors = Elsas LJ, Langley S, Steele E, Evinger J, Fridovich-Keil JL, Brown A, Singh R, Fernhoff P, Hjelm LN, Dembure PP | title = Galactosemia: a strategy to identify new biochemical phenotypes and molecular genotypes | journal = American Journal of Human Genetics | volume = 56 | issue = 3 | pages = 630–9 | date = mart 1995 | pmid = 7887416 | pmc = 1801164 }}
* {{cite journal | vauthors = Fridovich-Keil JL, Langley SD, Mazur LA, Lennon JC, Dembure PP, Elsas JL | title = Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family | journal = American Journal of Human Genetics | volume = 56 | issue = 3 | pages = 640–6 | date = mart 1995 | pmid = 7887417 | pmc = 1801186 }}
* {{cite journal | vauthors = Davit-Spraul A, Pourci ML, Ng KH, Soni T, Lemonnier A | title = Regulatory effects of galactose on galactose-1-phosphate uridyltransferase activity on human hepatoblastoma HepG2 cells | url = https://archive.org/details/sim_febs-letters_1994-11-07_354_2/page/n107 | journal = FEBS Letters | volume = 354 | issue = 2 | pages = 232–6 | date = novembar 1994 | pmid = 7957929 | doi = 10.1016/0014-5793(94)01133-8 | s2cid = 45242645 }}
* {{cite journal | vauthors = Lin HC, Kirby LT, Ng WG, Reichardt JK | title = On the molecular nature of the Duarte variant of galactose-1-phosphate uridyl transferase (GALT) | url = https://archive.org/details/sim_human-genetics_1994-02_93_2/page/167 | journal = Human Genetics | volume = 93 | issue = 2 | pages = 167–9 | date = februar 1994 | pmid = 8112740 | doi = 10.1007/BF00210604 | s2cid = 42558872 }}
* {{cite journal | vauthors = Elsas LJ, Dembure PP, Langley S, Paulk EM, Hjelm LN, Fridovich-Keil J | title = A common mutation associated with the Duarte galactosemia allele | journal = American Journal of Human Genetics | volume = 54 | issue = 6 | pages = 1030–6 | date = juni 1994 | pmid = 8198125 | pmc = 1918187 }}
* {{cite journal | vauthors = Reichardt JK, Novelli G, Dallapiccola B | title = Molecular characterization of the H319Q galactosemia mutation | journal = Human Molecular Genetics | volume = 2 | issue = 3 | pages = 325–6 | date = mart 1993 | pmid = 8499924 | doi = 10.1093/hmg/2.3.325 }}
{{refend}}

== Vanjski linkovi ==
* {{MeshName|Galactose-1-P-Uridyltransferase}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=galactosemia  GeneReviews/NIH/NCBI/UW entry on Galactosemia]  
* [http://www.arup.utah.edu/database/GALT/GALT_welcome.php Galactosemia (GALT) Mutation Database]
* [http://bioinformatica.isa.cnr.it/GALT/ GALT Protein Database] {{Webarchive|url=https://web.archive.org/web/20121109012213/http://bioinformatica.isa.cnr.it/GALT/ |date=9. 11. 2012 }}
* [https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P07902 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Galactose-1-phosphate uridylyltransferase
{{metabolizam fruktoze i galaktoze}}
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{{DEFAULTSORT:Galactose-1-phosphate uridylyltransferase}}
[[Kategorija:EC 2.7.7]]
[[Kategorija:Geni na hromosomu 9]]
[[Kategorija:Ljudski proteini]]
[[Kategorija:Proteomika]]