View source for Prorenin

'''Prorenin''' ({{IPAc-en|p|r|ə|ˈ|r|iː|n|ɪ|n}}<ref>{{Cite web|url=https://www.lexico.com/en/definition/renin|archive-url=https://web.archive.org/web/20191109153714/https://www.lexico.com/en/definition/renin|url-status=dead|archive-date=November 9, 2019|title=Renin &#124; Definition of Renin by Lexico|website=Lexico Dictionaries &#124; English}}</ref>) is a protein that constitutes a precursor for [[renin]],<ref name="aha">{{cite journal |last1=Jan Danser |first1=A.H. |title=Prorenin: Back Into the Arena |journal=Hypertension |date=May 2006 |volume=47 |issue=5 |pages=824–826 |doi=10.1161/01.HYP.0000215952.91959.4a |pmid=16585418 |doi-access=free }}</ref> the hormone that activates the [[renin–angiotensin system]], which serves to raise [[blood pressure]]. Prorenin is converted into renin by the [[juxtaglomerular cell]]s, which are specialised [[smooth muscle]] cells present mainly in the afferent, but also the efferent, [[arteriole]]s of the [[glomerulus|glomerular]] capillary bed.
Prorenin is a relatively large molecule, weighing approximately 46 [[KDa]].<ref name="pringle" />
==History==
Prorenin was discovered by [[Eugenie Lumbers]]<ref>{{cite journal |last1=Morrison |first1=Janna L. |last2=Lumbers |first2=Eugenie |last3=Bennet |first3=Laura |last4=Black |first4=Jane |title=Introduction: Celebrating Emeritus Scientia Professor Eugenie R Lumbers AM and Professor Caroline McMillen |journal=Clinical and Experimental Pharmacology and Physiology |date=November 2013 |volume=40 |issue=11 |pages=740–742 |doi=10.1111/1440-1681.12180 |pmid=24117727 |s2cid=44555887 }}</ref> in 1971.<ref>{{cite journal |last1=Lumbers |first1=ER |title=Activation of renin in human amniotic fluid by low pH. |journal=Enzymologia |date=30 June 1971 |volume=40 |issue=6 |pages=329–336 |pmid=4105386 }}</ref>
==Synthesis==
In addition to juxtaglomerular cells, prorenin is also synthesised by other organs, such as the adrenal glands, the ovaries, the testis and the pituitary gland, which is why it is found in the plasma of anephric individuals.<ref>{{cite journal |last1=Danser |first1=A. H. Jan |last2=Batenburg |first2=Wendy W. |last3=van Esch |first3=Joep H. M. |last4=Krop |first4=Manne |title=Prorenin anno 2008 |journal=Journal of Molecular Medicine |date=June 2008 |volume=86 |issue=6 |pages=655–658 |doi=10.1007/s00109-008-0318-2 |pmid=18322669 |pmc=2374880 }}</ref>
==Concentration==
Blood concentration levels of prorenin are between 5 and 10 times higher than those of renin.<ref name="aha" /> There is evidence to suggest that, in [[diabetes mellitus]], prorenin levels are even higher.<ref name="aha" /><ref name="sd">{{cite book |doi=10.1016/B978-0-12-801238-3.03982-9 |chapter=Renin and Prorenin |title=Encyclopedia of Endocrine Diseases |year=2019 |last1=Morganti |first1=Alberto |pages=478–482 |isbn=978-0-12-812200-6 |s2cid=102634216 }}</ref><ref>{{cite journal |last1=Jan Danser |first1=A. H. |last2=Batenburg |first2=W. W. |last3=van Esch |first3=J. H. M. |title=Prorenin and the (pro)renin receptor--an update |journal=Nephrology Dialysis Transplantation |date=8 March 2007 |volume=22 |issue=5 |pages=1288–1292 |doi=10.1093/ndt/gfl846 |pmid=17259648 |doi-access=free }}</ref> One study using relatively newer technology found that blood concentrations levels may be several order of magnitude higher than previously believed, and placing it at micrograms rather than nanograms per millilitre.<ref>{{cite journal |last1=Fujimoto |first1=Kazumi |last2=Kawamura |first2=Sayuki |last3=Bando |first3=Satoru |last4=Kamata |first4=Yuji |last5=Kodera |first5=Yoshio |last6=Shichiri |first6=Masayoshi |title=Circulating prorenin: its molecular forms and plasma concentrations |journal=Hypertension Research |date=June 2021 |volume=44 |issue=6 |pages=674–684 |doi=10.1038/s41440-020-00610-0 |pmid=33564180 |s2cid=231859379 }}</ref>
==Pregnancy==
Prorenin occurs in very high concentrations in [[amniotic fluid]] and [[amnion]].<ref name="pringle">{{cite journal |last1=Pringle |first1=Kirsty G. |last2=Wang |first2=Yu |last3=Lumbers |first3=Eugenie R. |title=The synthesis, secretion and uptake of prorenin in human amnion |journal=Physiological Reports |date=April 2015 |volume=3 |issue=4 |pages=e12313 |doi=10.14814/phy2.12313 |pmid=25902786 |pmc=4425950 }}</ref> It is secreted in large amounts from the [[placenta]] and womb, and from the ovaries.<ref>{{cite journal |last1=Wiegel |first1=Rosalieke E. |last2=von Versen-Höynck |first2=Frauke |last3=Steegers-Theunissen |first3=Régine P.M. |last4=Steegers |first4=Eric A.P. |last5=Danser |first5=A.H. Jan |title=Prorenin periconceptionally and in pregnancy: Does it have a physiological role? |journal=Molecular and Cellular Endocrinology |date=February 2021 |volume=522 |pages=111118 |doi=10.1016/j.mce.2020.111118 |pmid=33340569 |s2cid=229294165 |doi-access=free |hdl=1765/132984 |hdl-access=free }}</ref>
==Conversion to renin==
[[Proprotein convertase 1]] converts prorenin into renin,<ref>{{Cite web|url=https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/4/21/93.html|title=EC 3.4.21.93|website=www.qmul.ac.uk}}</ref> but proprotein convertase 2 does not.<ref>{{Cite web|url=https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/4/21/94.html|title=EC 3.4.21.94|website=www.qmul.ac.uk}}</ref>
There is no evidence that prorenin can be converted into renin in the circulation. Therefore, the granular (JG) cells seem to be the only source of active renin.<ref name="lote">{{cite book |doi=10.1007/978-1-4614-3785-7_9 |chapter=Regulation of Body Fluid Volume |title=Principles of Renal Physiology |year=2012 |last1=Lote |first1=Christopher J. |pages=105–119 |isbn=978-1-4614-3784-0 }}</ref>
==References==
{{Reflist}}
==External links==
* [https://www.rcsb.org/structure/3VCM RCSB PDB]
* [https://www.ebi.ac.uk/pdbe/entry/pdb/3vcm PDBe]
[[Category:Proteins]]