wiki143 - User contributions [en]

Product inhibition

2024-02-15T19:40:47Z

167.201.243.135: /* Reactor design */ Copy edit

{{Short description|Enzyme inhibition}}
'''Product inhibition''' is a type of [[enzyme inhibitor|enzyme inhibition]] where the product of an [[enzyme catalysis|enzyme reaction]] inhibits its production.<ref>{{cite book |doi=10.1002/9780470122709.ch4 |chapter=The Prevalence and Significance of the Product Inhibition of Enzymes|year=1963|editor-last=Nord|editor-first=F.F.|last1=Walter |first1=Charles |last2=Frieden |first2=Earl |title=Advances in Enzymology and Related Subjects of Biochemistry |volume=25 |pages=167–274 |pmid=14149677 |isbn=978-0-470-12270-9 }}</ref> Cells utilize product inhibition to regulate of [[metabolism]] as a form of [[negative feedback]] controlling [[metabolic pathway]]s.<ref>{{cite journal |last1=Hutson |first1=NJ |last2=Kerbey |first2=AL |last3=Randle |first3=PJ |last4=Sugden |first4=PH |title=Regulation of pyruvate dehydrogenase by insulin action |journal=Progress in Clinical and Biological Research |date=1979 |volume=31 |pages=707–719 |id={{NAID|10010916605}} |pmid=231784 }}</ref> Product inhibition is also an important topic in [[biotechnology]], as overcoming this effect can increase the yield of a product, such as an [[antibiotic]].<ref>{{cite journal |last1=Schügerl |first1=Karl |last2=Hubbuch |first2=Jürgen |title=Integrated bioprocesses |journal=Current Opinion in Microbiology |date=June 2005 |volume=8 |issue=3 |pages=294–300 |doi=10.1016/j.mib.2005.01.002 |pmid=15939352 }}</ref> Product inhibition can be [[Competitive inhibition|competitive]], [[Non-competitive inhibition|non-competitive]] or [[Uncompetitive inhibitor|uncompetitive.]]

== Mitigation of product inhibition ==

=== Reactor design ===
One method to reduce product inhibition is the use of a [[membrane reactor]].<ref>{{cite journal |last1=Fan |first1=Rong |last2=Ebrahimi |first2=Mehrdad |last3=Czermak |first3=Peter |title=Anaerobic Membrane Bioreactor for Continuous Lactic Acid Fermentation |journal=Membranes |date=3 May 2017 |volume=7 |issue=2 |pages=26 |doi=10.3390/membranes7020026 |pmid=28467384 |pmc=5489860 |doi-access=free }}</ref> These [[Bioreactor|bioreactors]] uses a membrane to separate products from the rest of the reactor, limiting their inhibition. If the product differs greatly in size from the cells producing it, and the [[Substrate (chemistry)|substrate]] feeding the cells, then the reactor can utilize a [[semipermeable membrane]] allowing to products to exit the reactor while leaving the cells and substrate behind to continue reacting making more product. Other reactor systems use chemical potential to separate products from the reactor, such as solubility of different compounds allowing one to pass through the membrane. Electrokinetic bioreactor systems have been developed which use [[electrolysis]], a process that uses electrical charge to remove the product from the bioreactor system.<ref>{{cite journal |last1=Li |first1=Hong |last2=Mustacchi |first2=Roberta |last3=Knowles |first3=Christopher J |last4=Skibar |first4=Wolfgang |last5=Sunderland |first5=Garry |last6=Dalrymple |first6=Ian |last7=Jackman |first7=Simon A |title=An electrokinetic bioreactor: using direct electric current for enhanced lactic acid fermentation and product recovery |journal=Tetrahedron |date=January 2004 |volume=60 |issue=3 |pages=655–661 |doi=10.1016/j.tet.2003.10.110 }}</ref>

'''External loop reactor''' uses current created by air bubbles flowing through the reactor to create a flow that brings the reactor contents through an external loop. A separating membrane can be placed in the external loop to collect product, and reduce product inhibition. A downside to external loop reactors is they create additional [[shear stress]].<ref name="Carstensen et al 2012">{{cite journal |last1=Carstensen |first1=Frederike |last2=Apel |first2=Andreas |last3=Wessling |first3=Matthias |title=In situ product recovery: Submerged membranes vs. external loop membranes |journal=Journal of Membrane Science |date=March 2012 |volume=394-395 |pages=1–36 |doi=10.1016/j.memsci.2011.11.029 }}</ref>
'''Submerged membrane''' bioreactors have the membrane contained within the main chamber of the bioreactor.<ref name="Carstensen et al 2012" />

A '''separative bioreactor''' is a type of [[continuous reactor]] where the producing cells are mounted on a resin membrane as to not flow out of the reactor as substrate is passed over them. The continuous flow of the reactor takes the product downstream as it is produced.<ref>{{cite journal |last1=Arora |first1=M. B. |last2=Hestekin |first2=J. A. |last3=Snyder |first3=S. W. |last4=St. Martin |first4=E. J. |last5=Lin |first5=Y. J. |last6=Donnelly |first6=M. I. |last7=Millard |first7=C. Sanville |title=The Separative Bioreactor: A Continuous Separation Process for the Simultaneous Production and Direct Capture of Organic Acids |journal=Separation Science and Technology |date=July 2007 |volume=42 |issue=11 |pages=2519–2538 |doi=10.1080/01496390701477238 |pmid=23723533 |pmc=3662075 }}</ref>

=== Other methods of mitigating product inhibition ===
'''Integrated''' '''liquid-liquid extraction''' can be used to remove products that have a [[density]] that differs from the rest of the bioreactors contents.<ref>{{cite journal |last1=Kaur |first1=Guneet |last2=Srivastava |first2=A.K. |last3=Chand |first3=Subhash |title=Debottlenecking product inhibition in 1,3-propanediol fermentation by In-Situ Product Recovery |journal=Bioresource Technology |date=December 2015 |volume=197 |pages=451–457 |doi=10.1016/j.biortech.2015.08.101 |pmid=26356117 }}</ref> This is done by adding a [[solvent]] downstream of the bioreactor and letting the product separate out in a settling tank before the bioreactor effluent is moved to a secondary reactor or returned to its initial reactor to continue its cultivation. This process can be done in batch or continuous operation.

'''Vacuum extraction'''<ref>{{cite journal |last1=Tavares |first1=Bruna |last2=Felipe |first2=Maria das Graças de Almeida |last3=dos Santos |first3=Júlio César |last4=Pereira |first4=Félix Monteiro |last5=Gomes |first5=Simone Damasceno |last6=Sene |first6=Luciane |title=An experimental and modeling approach for ethanol production by Kluyveromyces marxianus in stirred tank bioreactor using vacuum extraction as a strategy to overcome product inhibition |journal=Renewable Energy |date=February 2019 |volume=131 |pages=261–267 |doi=10.1016/j.renene.2018.07.030 }}</ref> can be used in fermentation to remove [[ethanol]] from a reactor. When the liquid in the vessel is placed in [[vacuum]] conditions the ethanol begins to [[Evaporation|evaporate]] because its more volatile than the rest of the reactor contents. This technique requires an acclimation period for the yeast in the reactor to adapt to the lower pressure environment.{{fact|date=March 2021}}

'''Product neutralization''' if a products inhibition due to its pH then it can be neutralized in the reactor and further processed downstream back into its original form.{{fact|date=March 2021}}

==References==
{{reflist}}

[[Category:Enzymes]]

HSP90AA2

2024-02-08T19:58:17Z

167.201.243.135: Italicized gene name

{{infobox protein
| Name = heat shock protein 90kDa alpha (cytosolic), class A member 2
| caption =
| image =
| width =
| HGNCid = 5256
| Symbol = HSP90AA2
| AltSymbols = HSPCAL3
| EntrezGene = 3324
| OMIM = 140575
| RefSeq = NM_001040141
| UniProt = Q14568
| PDB =
| ECnumber =
| Chromosome = 11
| Arm = p
| Band = 14.2-14.1
| LocusSupplementaryData =
}}
'''Heat shock protein 90kDa alpha (cytosolic), class A member 2''', also known as '''''HSP90AA2''''', is a human [[gene]].<ref name="pmid1740332">{{cite journal |vauthors=Ozawa K, Murakami Y, Eki T, Soeda E, Yokoyama K | title = Mapping of the gene family for human heat-shock protein 90 alpha to chromosomes 1, 4, 11, and 14 | journal = Genomics | volume = 12 | issue = 2 | pages = 214–20 |date=February 1992 | pmid = 1740332 | doi = 10.1016/0888-7543(92)90368-3 }}</ref> The [[protein]] encoded by this gene belongs to the [[Hsp90]] family of [[heat shock protein]]s.<ref name="pmid16269234">{{cite journal |vauthors=Chen B, Piel WH, Gui L, Bruford E, Monteiro A | title = The HSP90 family of genes in the human genome: insights into their divergence and evolution | journal = Genomics | volume = 86 | issue = 6 | pages = 627–37 |date=December 2005 | pmid = 16269234 | doi = 10.1016/j.ygeno.2005.08.012 | doi-access = free }}</ref>

==References==
{{Reflist}}

{{Chaperones}}

{{gene-11-stub}}

SIM1

2024-02-05T15:39:50Z

167.201.243.135: /* Interactions */ Copy edit

{{Short description|Genetic protein}}
{{Infobox gene}}
'''Single-minded homolog 1''', also known as '''class E basic helix-loop-helix protein 14''' (bHLHe14), is a [[protein]] that in humans is encoded by the ''SIM1'' [[gene]].<ref name="pmid9199934">{{cite journal | vauthors = Chrast R, Scott HS, Chen H, Kudoh J, Rossier C, Minoshima S, Wang Y, Shimizu N, Antonarakis SE | title = Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region | journal = Genome Research | volume = 7 | issue = 6 | pages = 615–24 | date = Jun 1997 | pmid = 9199934 | pmc = 310662 | doi = 10.1101/gr.7.6.615 }}</ref><ref name="pmid11448938">{{cite journal | vauthors = Michaud JL, Boucher F, Melnyk A, Gauthier F, Goshu E, Lévy E, Mitchell GA, Himms-Hagen J, Fan CM | title = Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus | journal = Human Molecular Genetics | volume = 10 | issue = 14 | pages = 1465–73 | date = Jul 2001 | pmid = 11448938 | doi = 10.1093/hmg/10.14.1465 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SIM1 single-minded homolog 1 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6492}}</ref>

==Function==
The ''SIM1'' and ''[[SIM2]]'' genes are homologs of ''[[Drosophila melanogaster]]'' single-minded (''sim''), so named because cells in the midline of the sim mutant embryo fail to properly develop and eventually die, and thus the paired longitudinal axon bundles that span the [[Drosophila embryogenesis#Anterior-posterior axis patterning in Drosophila|anterior-posterior axis]] of the embryo (analogous to the embryo's spinal cord) are collapsed into a "single" rudimentary axon bundle at the midline. SIM is a [[basic helix-loop-helix]]–[[PAS domain]] [[transcription factor]] that regulates gene expression in the midline cells. Because the ''sim'' gene plays an important role in ''Drosophila'' development and has peak levels of expression during the period of [[neurogenesis]], it was proposed that the human ''SIM2'' gene, which resides in a critical region of chromosome 21, is a candidate for involvement in certain dysmorphic features (particularly facial and skull characteristics), abnormalities of brain development, or mental retardation of [[Down syndrome]].<ref name="entrez"/>

==Clinical significance==
[[Haploinsufficiency]] of ''SIM1'' has been shown to cause severe early-onset obesity in a human girl with a ''de novo'' balanced translocation between chromosomes 1p22.1 and 6q16.2<ref name="pmid10587584">{{cite journal | vauthors = Holder JL, Butte NF, Zinn AR | title = Profound obesity associated with a balanced translocation that disrupts the SIM1 gene | journal = Human Molecular Genetics | volume = 9 | issue = 1 | pages = 101–8 | date = Jan 2000 | pmid = 10587584 | doi = 10.1093/hmg/9.1.101 | doi-access = free }}</ref> and has been suggested to cause a Prader-Willi-like phenotype in other cases.<ref name="pmid12161602">{{cite journal | vauthors = Faivre L, Cormier-Daire V, Lapierre JM, Colleaux L, Jacquemont S, Geneviéve D, Saunier P, Munnich A, Turleau C, Romana S, Prieur M, De Blois MC, Vekemans M | title = Deletion of the SIM1 gene (6q16.2) in a patient with a Prader-Willi-like phenotype | journal = Journal of Medical Genetics | volume = 39 | issue = 8 | pages = 594–6 | date = Aug 2002 | pmid = 12161602 | pmc = 1735217 | doi = 10.1136/jmg.39.8.594 }}</ref> Additionally, studies in mice have shown that haploinsufficiency of Sim1 causes obesity that is due to [[hyperphagia]] and do not respond properly to increased dietary fat.<ref name="pmid11448938" /><ref name="pmid14982752">{{cite journal | vauthors = Holder JL, Zhang L, Kublaoui BM, DiLeone RJ, Oz OK, Bair CH, Lee YH, Zinn AR | title = Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 287 | issue = 1 | pages = E105-13 | date = Jul 2004 | pmid = 14982752 | doi = 10.1152/ajpendo.00446.2003 }}</ref> Overexpression of ''SIM1'' protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice,<ref name="pmid16709610">{{cite journal | vauthors = Kublaoui BM, Holder JL, Tolson KP, Gemelli T, Zinn AR | title = SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake | journal = Endocrinology | volume = 147 | issue = 10 | pages = 4542–9 | date = Oct 2006 | pmid = 16709610 | doi = 10.1210/en.2006-0453 | doi-access = free }}</ref> who have disrupted [[melanocortin]] signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of [[Paraventricular nucleus|PVN]] neurons<ref name="pmid16728530">{{cite journal | vauthors = Kublaoui BM, Holder JL, Gemelli T, Zinn AR | title = Sim1 haploinsufficiency impairs melanocortin-mediated anorexia and activation of paraventricular nucleus neurons | journal = Molecular Endocrinology | volume = 20 | issue = 10 | pages = 2483–92 | date = Oct 2006 | pmid = 16728530 | doi = 10.1210/me.2005-0483 | doi-access = free }}</ref> and [[oxytocin]] deficiency in these mice.<ref name="pmid18451093">{{cite journal | vauthors = Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR | title = Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice | journal = Molecular Endocrinology | volume = 22 | issue = 7 | pages = 1723–34 | date = Jul 2008 | pmid = 18451093 | pmc = 2453606 | doi = 10.1210/me.2008-0067 }}</ref> It has been demonstrated that modulating SIM1 levels postnatally also leads to hyperphagia and obesity,<ref name="pmid20220015">{{cite journal | vauthors = Tolson KP, Gemelli T, Gautron L, Elmquist JK, Zinn AR, Kublaoui BM | title = Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression | journal = The Journal of Neuroscience | volume = 30 | issue = 10 | pages = 3803–12 | date = Mar 2010 | pmid = 20220015 | pmc = 3285557 | doi = 10.1523/JNEUROSCI.5444-09.2010 }}</ref><ref name="pmid16807340">{{cite journal | vauthors = Yang C, Gagnon D, Vachon P, Tremblay A, Levy E, Massie B, Michaud JL | title = Adenoviral-mediated modulation of Sim1 expression in the paraventricular nucleus affects food intake | journal = The Journal of Neuroscience | volume = 26 | issue = 26 | pages = 7116–20 | date = Jun 2006 | pmid = 16807340 | pmc = 6673926| doi = 10.1523/JNEUROSCI.0672-06.2006 | doi-access = free }}</ref> suggesting a physiological role for SIM1 separate from its role in development.

==Interactions==
SIM1 has been shown to [[Protein-protein interaction|interact]] with [[aryl hydrocarbon receptor nuclear translocator]].<ref name=pmid9020169>{{cite journal | vauthors = Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O | title = Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4451–7 | date = Feb 1997 | pmid = 9020169 | doi = 10.1074/jbc.272.7.4451 | doi-access = free }}</ref><ref name=pmid11782478>{{cite journal | vauthors = Woods SL, Whitelaw ML | title = Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors | journal = The Journal of Biological Chemistry | volume = 277 | issue = 12 | pages = 10236–43 | date = Mar 2002 | pmid = 11782478 | doi = 10.1074/jbc.M110752200 | doi-access = free }}</ref>

==References==
{{reflist}}

==Further reading==
{{refbegin}}
* {{cite journal | vauthors = Fan CM, Kuwana E, Bulfone A, Fletcher CF, Copeland NG, Jenkins NA, Crews S, Martinez S, Puelles L, Rubenstein JL, Tessier-Lavigne M | title = Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome | journal = Molecular and Cellular Neurosciences | volume = 7 | issue = 1 | pages = 1–16 | date = Jan 1996 | pmid = 8812055 | doi = 10.1006/mcne.1996.0001 | s2cid = 11411254 }}
* {{cite journal | vauthors = Probst MR, Fan CM, Tessier-Lavigne M, Hankinson O | title = Two murine homologs of the Drosophila single-minded protein that interact with the mouse aryl hydrocarbon receptor nuclear translocator protein | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4451–7 | date = Feb 1997 | pmid = 9020169 | doi = 10.1074/jbc.272.7.4451 | doi-access = free }}
* {{cite journal | vauthors = Holder JL, Butte NF, Zinn AR | title = Profound obesity associated with a balanced translocation that disrupts the SIM1 gene | journal = Human Molecular Genetics | volume = 9 | issue = 1 | pages = 101–8 | date = Jan 2000 | pmid = 10587584 | doi = 10.1093/hmg/9.1.101 | doi-access = free }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = Nov 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Woods SL, Whitelaw ML | title = Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors | journal = The Journal of Biological Chemistry | volume = 277 | issue = 12 | pages = 10236–43 | date = Mar 2002 | pmid = 11782478 | doi = 10.1074/jbc.M110752200 | doi-access = free }}
* {{cite journal | vauthors = Faivre L, Cormier-Daire V, Lapierre JM, Colleaux L, Jacquemont S, Geneviéve D, Saunier P, Munnich A, Turleau C, Romana S, Prieur M, De Blois MC, Vekemans M | title = Deletion of the SIM1 gene (6q16.2) in a patient with a Prader-Willi-like phenotype | journal = Journal of Medical Genetics | volume = 39 | issue = 8 | pages = 594–6 | date = Aug 2002 | pmid = 12161602 | pmc = 1735217 | doi = 10.1136/jmg.39.8.594 }}
* {{cite journal | vauthors = Yamaki A, Kudoh J, Shimizu N, Shimizu Y | title = A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2 | journal = Biochemical and Biophysical Research Communications | volume = 313 | issue = 3 | pages = 482–8 | date = Jan 2004 | pmid = 14697214 | doi = 10.1016/j.bbrc.2003.11.168 | doi-access = free }}
* {{cite journal | vauthors = Meyre D, Lecoeur C, Delplanque J, Francke S, Vatin V, Durand E, Weill J, Dina C, Froguel P | title = A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2 | journal = Diabetes | volume = 53 | issue = 3 | pages = 803–11 | date = Mar 2004 | pmid = 14988267 | doi = 10.2337/diabetes.53.3.803 | doi-access = free }}
* {{cite journal | vauthors = Kublaoui BM, Holder JL, Tolson KP, Gemelli T, Zinn AR | title = SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake | journal = Endocrinology | volume = 147 | issue = 10 | pages = 4542–9 | date = Oct 2006 | pmid = 16709610 | doi = 10.1210/en.2006-0453 | doi-access = free }}
{{refend}}

{{Transcription factors|g1}}

[[Category:PAS-domain-containing proteins]]

Epididymal secretory protein E1

2024-02-02T20:38:22Z

167.201.243.135: Copy editing

{{protein
|Name=Niemann-Pick disease, type C2
|caption=
|image=
|width=
|HGNCid=14537
|Symbol=NPC2
|AltSymbols=
|EntrezGene=10577
|OMIM=601015
|RefSeq=NM_006432
|UniProt=P61916
|PDB=
|ECnumber=
|Chromosome=14
|Arm=q
|Band=24.3
|LocusSupplementaryData=
}}
The '''epididymal secretory protein E1''', also known as '''NPC2''' (Niemann-Pick intracellular cholesterol transporter 2), is one of two main lysosomal transport proteins that assist in the regulation of cellular cholesterol by exportation of LDL-derived [[cholesterol]] from [[Lysosome|lysosomes]].<ref name=":1">{{cite journal | vauthors = Infante RE, Wang ML, Radhakrishnan A, Kwon HJ, Brown MS, Goldstein JL | title = NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 40 | pages = 15287–15292 | date = October 2008 | pmid = 18772377 | pmc = 2563079 | doi = 10.1073/pnas.0807328105 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Li X, Saha P, Li J, Blobel G, Pfeffer SR | title = Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 36 | pages = 10079–10084 | date = September 2016 | pmid = 27551080 | pmc = 5018801 | doi = 10.1073/pnas.1611956113 | bibcode = 2016PNAS..11310079L | doi-access = free }}</ref> Lysosomes have digestive enzymes that allow it to break down LDL particles to LDL-derived cholesterol once the LDL particle is engulfed into the cell via [[Receptor-mediated endocytosis|receptor mediated endocytosis]].{{Short description|Group of transport proteins in vertebrates}}
NPC2 works cooperatively with the [[NPC1]] protein to facilitate the exportation of LDL-derived cholesterol out of the lysosome to regulate the concentrations of lipids and cholesterol in the body.<ref name=":1" /> Epididymal secretory protein E1 is a protein associated with [[Niemann-Pick disease, type C]], which is one of the 3 types of the [[Niemann–Pick disease|Niemann-Pick diseases]] (Type A, B, and C).<ref name=":0" /> This disease can lead to an over accumulation of [[cholesterol]] and [[Lipid|lipids]] in different types of tissues, including the brain.<ref name=":0" /> <ref name=":2" /> It is caused by a mutation in the ''NPC2'' gene that impairs the body's ability to transport [[Lipid|lipids]] or [[cholesterol]] intracellularly.<ref name=":2">{{Cite web |title=Niemann Pick Disease Type C |url=https://rarediseases.org/rare-diseases/niemann-pick-disease-type-c/ |access-date=2022-04-28 |website=NORD (National Organization for Rare Disorders) |language=en-US}}</ref>

== Structure ==
[[File:PDB 1nep EBI.jpg|thumb|Bovine NPC2/Epididymal secretory protein E1 3D structure]]

The epididymal secretory protein E1 is a small soluble glycoprotein consisting of 132 amino acids that is found in a large variety of cells.<ref name=":3" />

== Function ==

Lysosomal secretion of cholesterol is one part of the regulation of cholesterol in the body. LDL particles are low density lipoproteins that carry cholesterol to cells. LDL particles are engulfed into cells by [[receptor-mediated endocytosis]]. Once the LDL is engulfed this results in the budding of the receptors to disassemble from the LDL vesicle and move back up to the outer membrane of the cell. This is due to the pH on the outside of the cell being less acidic than the inside of the cell. After this budding process the [[lysosome]]s fuse with LDL particles. Lysosomes break down the [[Low-density lipoprotein|LDL]] into cholesterol and other lipids (fatty acids), hence LDL-derived [[cholesterol]]. The epididymal secretory protein E1 (NPC2) is produced via transcription of the ''NPC2'' gene and recruits and transfers the LDL-derived cholesterol to the sterol-binding pocket in the [[N-terminal]] domain of the NPC1 protein to be transferred from the lysosome lumen and excreted from the lysosome [[membrane]].<ref name=":0" /><ref>{{Cite web |title=NPC2 Gene - GeneCards {{!}} NPC2 Protein {{!}} NPC2 Antibody |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=NPC2 |access-date=2022-04-28 |website=www.genecards.org}}</ref>

== Clinical significance ==
Since the epididymal secretory protein E1 plays a role in the intracellular transport of cholesterol, a mutation in the gene that produces it (''NPC2'' gene) can cause serious issues that lead to [[Niemann-Pick disease, type C]].<ref name=":0">{{Cite web |title="NPC2 - NPC intracellular cholesterol transporter 2 precursor - Homo sapiens (Human) - NPC2 gene & protein" |url=https://www.uniprot.org/uniprot/P61916}}</ref> [[Niemann-Pick disease, type C]] is a rare disorder that results in the over accumulation of lipids and cholesterol in different types of tissues in the body due to this protein being ubiquitous.<ref name=":2" /><ref name=":3">{{cite journal | vauthors = Vanier MT, Millat G | title = Structure and function of the NPC2 protein | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1685 | issue = 1–3 | pages = 14–21 | date = October 2004 | pmid = 15465422 | doi = 10.1016/j.bbalip.2004.08.007 }}</ref> Symptoms vary per individual and can be fatal at birth or go undiagnosed up until adulthood.<ref name=":0" />

== See also ==
* [[NPC1]]
* [[Low-density lipoprotein|Low density lipoproteins]]
* [[Receptor-mediated endocytosis|Receptor mediated endocytosis]]
* [[Hypercholesterolemia]]

== References ==
{{Reflist}}

== Further reading ==
* Belleannée C, Labas V, Teixeira-Gomes AP, Gatti JL, Dacheux JL, Dacheux F. Identification of luminal and secreted proteins in bull epididymis. Journal of Proteomics. 2011. doi:10.1016/j.jprot.2010.07.013
* Boe-Hansen GB, Rego JPA, Crisp JM, Moura AA, Nouwens AS, Li Y, Venus B, Burns BM, McGowan MR. Seminal plasma proteins and their relationship with percentage of morphologically normal sperm in 2-year-old Brahman (Bos indicus) bulls. Animal Reproduction Science. 2015. doi:10.1016/j.anireprosci.2015.09.003

== External links ==
* {{MeshName|NPC2+protein,+human}}

{{Protein-stub}}

Template:Digestive system neoplasia

2024-01-30T21:35:30Z

167.201.243.135: Formatting

{{Navbox
| name = Digestive system neoplasia
| title = [[Digestive system neoplasm|Digestive system neoplasia]]
| state = {{{state|autocollapse}}}
| listclass = hlist

| group1 = [[Human gastrointestinal tract|GI tract]]
| list1 =
{{Navbox|subgroup

| group1 = [[Upper alimentary tract#Upper gastrointestinal tract|Upper]]
| list1 =
{{Navbox|subgroup

| group1 = [[Esophageal cancer|Esophagus]]
| list1 =
* [[Squamous cell carcinoma]]
* [[Adenocarcinoma]]

| group2 = [[Stomach cancer|Stomach]]
| list2 =
* [[Gastric carcinoma]]
* [[Signet ring cell carcinoma]]
* [[Gastric lymphoma]]
** [[MALT lymphoma]]
* [[Linitis plastica]]
* [[Hereditary diffuse gastric cancer]]
}}

| group2 = [[Human gastrointestinal tract#Lower gastrointestinal tract|Lower]]
| list2 =
{{Navbox|subgroup

| group1 = [[Small intestine cancer|Small intestine]]
| list1 =
* [[Duodenal cancer]]
** [[Adenocarcinoma]]

| group2 = [[Appendix cancer|Appendix]]
| list2 =
* [[Carcinoid]]
* [[Pseudomyxoma peritonei]]

| group3 = [[Colorectal cancer|Colon/rectum]]
| list3 =
* ''[[Colorectal polyp]]:'' [[Colorectal adenoma|adenoma]], [[hyperplastic polyp|hyperplastic]], [[Juvenile polyp|juvenile]], [[sessile serrated adenoma]], [[traditional serrated adenoma]], [[Peutz–Jeghers syndrome|Peutz–Jeghers]], [[Cronkhite–Canada syndrome|Cronkhite–Canada]]

* ''Polyposis syndromes:'' [[Juvenile polyposis syndrome|Juvenile]]
* [[MUTYH-associated polyposis|MUTYH-associated]]
* [[Familial adenomatous polyposis|Familial adenomatous]]/[[Gardner's syndrome|Gardner's]]
* [[Polymerase proofreading-associated polyposis|Polymerase proofreading-associated]]
* [[Serrated polyposis syndrome|Serrated polyposis]]

* ''Neoplasm:'' [[Adenocarcinoma]]
* [[Familial adenomatous polyposis]]
* [[Hereditary nonpolyposis colorectal cancer]]

| group4 = [[Anal cancer|Anus]]
| list4 =
* [[Squamous cell carcinoma]]
}}

| group3 = Upper and/or lower
| list3 =
* [[Gastrointestinal stromal tumor]]
* [[Krukenberg tumor|Krukenberg tumor (metastatic)]]

}}

| group2 = [[Accessory digestive gland|Accessory]]
| list2 =
{{Navbox|subgroup

| group1 = [[Liver tumor|Liver]]
| list1 =
* ''[[malignant]]:'' [[Hepatocellular carcinoma]]
** [[Fibrolamellar hepatocellular carcinoma|Fibrolamellar]]
* [[Hepatoblastoma]]
* [[Liver angiosarcoma]]

* ''[[Benign tumor|benign]]:'' [[Hepatocellular adenoma]]
* [[Cavernous hemangioma]]

* ''[[hyperplasia]]:'' [[Focal nodular hyperplasia]]
* [[Nodular regenerative hyperplasia]]

| group2 = [[Biliary tract]]
| list2 =
* ''[[bile duct]]:'' [[Cholangiocarcinoma]]
* [[Klatskin tumor]]

* ''[[gallbladder]]:'' [[Gallbladder cancer]]

| group3 = [[Pancreatic cancer|Pancreas]]
| list3 =
* ''[[exocrine pancreas]]:'' [[Adenocarcinoma]]
* [[Pancreatic ductal carcinoma]]

* ''[[cyst]]ic [[neoplasm]]s'': [[Serous microcystic adenoma]]
* [[Intraductal papillary mucinous neoplasm]]
* [[pancreatic mucinous cystic neoplasm|Mucinous cystic neoplasm]]
* [[Solid pseudopapillary neoplasm]]

* [[Pancreatoblastoma]]
}}

| group3 = [[Peritoneum]]
| list3 =
* [[Primary peritoneal carcinoma]]
* [[Peritoneal mesothelioma]]
* [[Desmoplastic small round cell tumor]]

}}<noinclude>
{{Documentation|content=
==Parameters==
{{Collapsible option}}
==See also==
* [[:Category:Digestive system neoplasia]]

[[Category:Oncology navigational boxes]]
}}</noinclude>