Unutrašnji faktor

CBLIF
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2PMV, 3KQ4
Identifikatori
Aliasi	CBLIF
Vanjski ID-jevi	OMIM: 609342 MGI: 1202394 HomoloGene: 3773 GeneCards: CBLIF
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	59,845,499 bp
Lokacija gena (miš)
Hrom.	Hromosom 19 (miš)
Kraj	11,740,811 bp
Ontologija gena
Molekularna funkcija	• cobalamin binding;
Ćelijska komponenta	• extracellular region; • microvillus; • endozom; • lysosomal lumen; • apical plasma membrane; • Vanćelijsko;
Biološki proces	• cobalt ion transport; • ion transport; • cobalamin transport; • cobalamin metabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	2694
	14603
	ENSG00000134812
	ENSMUSG00000024682
	P27352
	P52787
	NM_005142
	NM_008118
	NP_005133
	NP_032144
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Unutrašnji faktor ili intrizični faktor (IF), kobalamin vezujući unutrašnji faktor,^[5] znan I kao želučani unutrašnji faktor (GIF), jest glikoprotein koji je kod ljudi kodiran genom CBLIF sa hromosoma 11. Kod ljudi proizvode ga parijetalne ćelije ili glavne ćelije (kod glodara) želuca. Neophodan je za apsorpciju vitamina B₁₂ kasnije u distalnom ileumskom tankom crevu.^[5]^[6]

Haptokorin (transkobalamin I) je još jedan glikoprotein koji luče pljuvačne žlijezde i koji se vezuje za vitamin B₁₂. Vitamin B₁₂ je osjetljiv na kiselinu i vezujući se za haptokorin može sigurno proći kroz kiseli želudac do dvanaestopalačnog crijeva.^[7] U manje kiseloj sredini duodenuma, enzimi gušterače probavljaju glikoproteinski nosač i vitamin B₁₂ se tada može vezati za unutrašnji faktor.^[7] Ovaj novi kompleks zatim apsorbuju epitelne ćelije (enterociti) ileuma.^[7] Unutar ćelija, vitamin B₁₂ se ponovo disocira i vezuje za drugi protein, transkobalamin II; novi kompleks tada može izaći iz epitelnih ćelija da se prenese u jetru.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 417 aminokiselina, a molekulska težina 45.416 Da.

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAWFALYLLS	LLWATAGTST	QTQSSCSVPS	AQEPLVNGIQ	VLMENSVTSS
AYPNPSILIA	MNLAGAYNLK	AQKLLTYQLM	SSDNNDLTIG	QLGLTIMALT
SSCRDPGDKV	SILQRQMENW	APSSPNAEAS	AFYGPSLAIL	ALCQKNSEAT
LPIAVRFAKT	LLANSSPFNV	DTGAMATLAL	TCMYNKIPVG	SEEGYRSLFG
QVLKDIVEKI	SMKIKDNGII	GDIYSTGLAM	QALSVTPEPS	KKEWNCKKTT
DMILNEIKQG	KFHNPMSIAQ	ILPSLKGKTY	LDVPQVTCSP	DHEVQPTLPS
NPGPGPTSAS	NITVIYTINN	QLRGVELLFN	ETINVSVKSG	SVLLVVLEEA
QRKNPMFKFE	TTMTSWGLVV	SSINNIAENV	NHKTYWQFLS	GVTPLNEGVA
DYIPFNHEHI	TANFTQY

Mjesto lučenja

Unutrašnji faktor luči želudac, pa je prisutan u želučanom soku kao i u sluzokoži želuca.^[9] The optimum pH for its action is approximately 7.^[10] Njegova koncentracija nije u korelaciji sa količinom HCl ili pepsina u želučanom soku, npr. unutrašnji faktor može biti prisutan čak i kada je pepsin u velikoj mjeri odsutan.^[11] Mjesto formiranja unutrašnjeg faktora varira kod različitih vrsta. Kod svinja se dobija iz pilorusa i početka duodenuma.^[12] kod ljudi je prisutan u fundusu i tijelu želuca.^[13]

Ograničena količina normalnog ljudskog želučanog unutrašnjeg faktora ograničava normalnu efikasnu apsorpciju B₁₂ na oko 2 μg po obroku, što je nominalno adekvatan unos B₁₂.^[14]

Insuficijencija

U opakoj anemiji, koja je obično autoimunska bolest, autoantitijela usmjerena protiv intrinzičnog faktora ili samih parijetalnih ćelija dovode do nedostatka unutrašnjeg faktora, malapsorpcije vitamina B< sub>12 i kasnija megaloblastna anemija.^[15] Atrofijski gastritis također može uzrokovati nedostatak unutrašnjeg faktora i anemiju, oštećenjem parijetalnih ćelija zida želuca.^[16] Egzokrina pankreasna insuficijencija može ometati normalnu disocijaciju vitamina B₁₂ od njegovih vezujućih proteina u tankom crijevu, sprječavajući apsorpciju preko kompleksa unutrašnjeg faktora.^[17]

Mutacije u "GIF" genu odgovorne su za rijetku nasljednu bolest zvanu "nedostatak unutrašnjeg faktora"^[18] što rezultira malapsorpcijom vitamina B₁₂.^[19]

Tretman

Za liječenje perniciozne anemije, u većini zemalja, koriste se intramuskularne injekcije vitamina B₁₂^[20] Oralno primijenjen vitamin B₁₂ apsorbira se bez unutrašnjeg faktora, ali na nivoima manjim od jednog procenta nego ako je prisutan intrinzični faktor.^[21] Uprkos malim apsorbovanim količinama, oralna terapija vitaminom B₁₂ je efikasna u smanjenju simptoma perniciozne anemije.^[22] Vitamin B₁₂ se također može davati podjezično, ali nema dokaza da je ovaj način primjene bolji od oralnog,^[23] and only Canada and Sweden routinely prescribe this route of administration.^[20]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134812 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024682 - Ensembl, maj 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.
^ ^a ^b "CBLIF - Cobalamin binding intrinsic factor precursor - Homo sapiens (Human) - CBLIF gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 15. 3. 2022.
^ Pocock G, Richards C (2006). Human Physiology: The Basis of Medicine (3rd izd.). Oxford University Press. str. 230. ISBN 978-019-856878-0.
^ ^a ^b ^c Fedosov SN (2012). "Physiological and molecular aspects of cobalamin transport". Water Soluble Vitamins. (review). Subcellular Biochemistry. 56. str. 347–67. doi:10.1007/978-94-007-2199-9_18. ISBN 978-94-007-2198-2. PMID 22116708.
^ Alpers DH, Russell-Jones G (maj 2013). "Gastric intrinsic factor: the gastric and small intestinal stages of cobalamin absorption. A personal journey". (review). Biochimie. 95 (5): 989–94. doi:10.1016/j.biochi.2012.12.006. PMID 23274574.
^ Sharma K (2016). "Gastrointestinal System". u Talwar G, Hasnain SE, Sarin SK (ured.). Textbook Of Biochemistry, Biotechnology, Allied And Molecular Medicine. (secondary) (4th izd.). PHI Learning Private Limited. str. 632. ISBN 978-81-203-5125-7.
^ Shum HY, O'Neill BJ, Streeter AM (1971). "Effect of pH changes on the binding of vitamin B12 by intrinsic factor". Journal of Clinical Pathology. 24 (3): 239–43. doi:10.1136/jcp.24.3.239. PMC 476962. PMID 5103294.
^ Poliner IJ, Spiro HM, Pask BA, Trocchio N (1958). "The independent secretion of acid, pepsin, and intrinsic factor by the human stomach". (primary). Gastroenterology. 34 (2): 196–209. doi:10.1016/S0016-5085(58)80102-X. PMID 13512593.
^ Heatley NG, Florey H, Turnbull A, Jennings MA, Watson GM, Wakisaka G, Witts LJ (1954). "Intrinsic factor in the pyloric and duodenal secretions of the pig". (primary). Lancet. 267 (6838): 578–80. doi:10.1016/S0140-6736(54)90355-4. PMID 13193076.
^ Howard TA, Misra DN, Grove M, Becich MJ, Shao JS, Gordon M, Alpers DH (1996). "Human gastric intrinsic factor expression is not restricted to parietal cells". (primary). Journal of Anatomy. 189 (Pt 2): 303–13. PMC 1167747. PMID 8886952.
^ Watanabe F (Nov 2007). "Vitamin B12 sources and bioavailability". (review). Experimental Biology and Medicine. 232 (10): 1266–74. doi:10.3181/0703-MR-67. PMID 17959839. S2CID 14732788.
^ Osborne D, Sobczyńska-Malefora A (2015). "Autoimmune mechanisms in pernicious anaemia & thyroid disease". (review). Autoimmunity Reviews. 14 (9): 763–8. doi:10.1016/j.autrev.2015.04.011. PMID 25936607.
^ Neumann WL, Coss E, Rugge M, Genta RM (2013). "Autoimmune atrophic gastritis--pathogenesis, pathology and management". (review). Nature Reviews. Gastroenterology & Hepatology. 10 (9): 529–41. doi:10.1038/nrgastro.2013.101. PMID 23774773. S2CID 205487577.
^ Guéant JL, Champigneulle B, Gaucher P, Nicolas JP (1990). "Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child". (review). Pancreas. 5 (5): 559–67. doi:10.1097/00006676-199009000-00011. PMID 2235967. S2CID 9077477.
^ "Intrinsic factor deficiency | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Arhivirano s originala, 27. 5. 2022. Pristupljeno 30. 3. 2022.
^ Kozyraki R, Cases O (2013). "Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders". (review). Biochimie. 95 (5): 1002–7. doi:10.1016/j.biochi.2012.11.004. PMID 23178706.
^ ^a ^b Shipton MJ, Thachil J (2015). "Vitamin B12 deficiency - A 21st century perspective". (review). Clinical Medicine. 15 (2): 145–50. doi:10.7861/clinmedicine.15-2-145. PMC 4953733. PMID 25824066.
^ Alpers DH (Mar 2005). "What is new in vitamin B(12)?". (review). Current Opinion in Gastroenterology. 21 (2): 183–6. doi:10.1097/01.mog.0000148331.96932.44. PMID 15711210.
^ Andrès E, Fothergill H, Mecili M (2010). "Efficacy of oral cobalamin (vitamin B12) therapy". (review). Expert Opinion on Pharmacotherapy. 11 (2): 249–56. doi:10.1517/14656560903456053. PMID 20088746. S2CID 37088496.
^ Sharabi A, Cohen E, Sulkes J, Garty M (2003). "Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route". (primary). British Journal of Clinical Pharmacology. 56 (6): 635–8. doi:10.1046/j.1365-2125.2003.01907.x. PMC 1884303. PMID 14616423.

Dopunska literatura

Devalia V, Hamilton MS, Molloy AM (Aug 2014). "Guidelines for the diagnosis and treatment of cobalamin and folate disorders". (review). British Journal of Haematology. 166 (4): 496–513. doi:10.1111/bjh.12959. PMID 24942828. S2CID 5772424.
Coati I, Fassan M, Farinati F, Graham DY, Genta RM, Rugge M (Nov 2015). "Autoimmune gastritis: Pathologist's viewpoint". (review). World Journal of Gastroenterology. 21 (42): 12179–89. doi:10.3748/wjg.v21.i42.12179. PMC 4641135. PMID 26576102.
Quadros EV (Jan 2010). "Advances in the understanding of cobalamin assimilation and metabolism". (review). British Journal of Haematology. 148 (2): 195–204. doi:10.1111/j.1365-2141.2009.07937.x. PMC 2809139. PMID 19832808.
Christensen EI, Nielsen R, Birn H (Feb 2013). "From bowel to kidneys: the role of cubilin in physiology and disease". (review). Nephrology, Dialysis, Transplantation. 28 (2): 274–81. doi:10.1093/ndt/gfs565. PMID 23291372.

Vanjski linkovi

Intrinsic factor na US National Library of Medicine Medical Subject Headings (MeSH)

MedlinePlus Encyclopedia: 002381

Overview at colostate.edu Arhivirano 9. 6. 2020. na Wayback Machine
P27352

Šablon:Gastrointestinalna fiziologija Šablon:Mukoproteini

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134812 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024682 - Ensembl, maj 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.

[uniprot-5] "CBLIF - Cobalamin binding intrinsic factor precursor - Homo sapiens (Human) - CBLIF gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 15. 3. 2022.

[Pocock_2006-6] Pocock G, Richards C (2006). Human Physiology: The Basis of Medicine (3rd izd.). Oxford University Press. str. 230. ISBN 978-019-856878-0.

[Fedosov_2012-7] Fedosov SN (2012). "Physiological and molecular aspects of cobalamin transport". Water Soluble Vitamins. (review). Subcellular Biochemistry. 56. str. 347–67. doi:10.1007/978-94-007-2199-9_18. ISBN 978-94-007-2198-2. PMID 22116708.

[Alpers_2013-8] Alpers DH, Russell-Jones G (maj 2013). "Gastric intrinsic factor: the gastric and small intestinal stages of cobalamin absorption. A personal journey". (review). Biochimie. 95 (5): 989–94. doi:10.1016/j.biochi.2012.12.006. PMID 23274574.

[Sharma_2016-9] Sharma K (2016). "Gastrointestinal System". u Talwar G, Hasnain SE, Sarin SK (ured.). Textbook Of Biochemistry, Biotechnology, Allied And Molecular Medicine. (secondary) (4th izd.). PHI Learning Private Limited. str. 632. ISBN 978-81-203-5125-7.

[Shum_1971-10] Shum HY, O'Neill BJ, Streeter AM (1971). "Effect of pH changes on the binding of vitamin B12 by intrinsic factor". Journal of Clinical Pathology. 24 (3): 239–43. doi:10.1136/jcp.24.3.239. PMC 476962. PMID 5103294.

[pmid13512593-11] Poliner IJ, Spiro HM, Pask BA, Trocchio N (1958). "The independent secretion of acid, pepsin, and intrinsic factor by the human stomach". (primary). Gastroenterology. 34 (2): 196–209. doi:10.1016/S0016-5085(58)80102-X. PMID 13512593.

[pmid13193076-12] Heatley NG, Florey H, Turnbull A, Jennings MA, Watson GM, Wakisaka G, Witts LJ (1954). "Intrinsic factor in the pyloric and duodenal secretions of the pig". (primary). Lancet. 267 (6838): 578–80. doi:10.1016/S0140-6736(54)90355-4. PMID 13193076.

[pmid8886952-13] Howard TA, Misra DN, Grove M, Becich MJ, Shao JS, Gordon M, Alpers DH (1996). "Human gastric intrinsic factor expression is not restricted to parietal cells". (primary). Journal of Anatomy. 189 (Pt 2): 303–13. PMC 1167747. PMID 8886952.

[14] Watanabe F (Nov 2007). "Vitamin B12 sources and bioavailability". (review). Experimental Biology and Medicine. 232 (10): 1266–74. doi:10.3181/0703-MR-67. PMID 17959839. S2CID 14732788.

[pmid25936607-15] Osborne D, Sobczyńska-Malefora A (2015). "Autoimmune mechanisms in pernicious anaemia & thyroid disease". (review). Autoimmunity Reviews. 14 (9): 763–8. doi:10.1016/j.autrev.2015.04.011. PMID 25936607.

[pmid23774773-16] Neumann WL, Coss E, Rugge M, Genta RM (2013). "Autoimmune atrophic gastritis--pathogenesis, pathology and management". (review). Nature Reviews. Gastroenterology & Hepatology. 10 (9): 529–41. doi:10.1038/nrgastro.2013.101. PMID 23774773. S2CID 205487577.

[pmid2235967-17] Guéant JL, Champigneulle B, Gaucher P, Nicolas JP (1990). "Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child". (review). Pancreas. 5 (5): 559–67. doi:10.1097/00006676-199009000-00011. PMID 2235967. S2CID 9077477.

[gard-18] "Intrinsic factor deficiency | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Arhivirano s originala, 27. 5. 2022. Pristupljeno 30. 3. 2022.

[pmid23178706-19] Kozyraki R, Cases O (2013). "Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders". (review). Biochimie. 95 (5): 1002–7. doi:10.1016/j.biochi.2012.11.004. PMID 23178706.

[Shipton_2015-20] Shipton MJ, Thachil J (2015). "Vitamin B12 deficiency - A 21st century perspective". (review). Clinical Medicine. 15 (2): 145–50. doi:10.7861/clinmedicine.15-2-145. PMC 4953733. PMID 25824066.

[21] Alpers DH (Mar 2005). "What is new in vitamin B(12)?". (review). Current Opinion in Gastroenterology. 21 (2): 183–6. doi:10.1097/01.mog.0000148331.96932.44. PMID 15711210.

[pmid20088746-22] Andrès E, Fothergill H, Mecili M (2010). "Efficacy of oral cobalamin (vitamin B12) therapy". (review). Expert Opinion on Pharmacotherapy. 11 (2): 249–56. doi:10.1517/14656560903456053. PMID 20088746. S2CID 37088496.

[pmid14616423-23] Sharabi A, Cohen E, Sulkes J, Garty M (2003). "Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route". (primary). British Journal of Clinical Pharmacology. 56 (6): 635–8. doi:10.1046/j.1365-2125.2003.01907.x. PMC 1884303. PMID 14616423.

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