User:Jcorelite/Angiotensin
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Angiotensinogen[edit]
Angiotensinogen is an α-2-globulin synthesized in the liver[1] and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides.[2] It is a member of the serpin family of proteins, leading to another name: Serpin A8,[3] although it is not known to inhibit other enzymes like most serpins. In addition, a generalized crystal structure can be estimated by examining other proteins of the serpin family, but angiotensinogen has an elongated N-terminus compared to other serpin family proteins.[4] Obtaining actual crystals for X-ray diffractometric analysis is difficult in part due to the variability of glycosylation that Angiotensinogen exhibits. The non-glycosylated and fully glycosylated states of angiotensinogen also vary in molecular weight, the former weighing 53kDa and the latter weighing 75kDa, with a plethora of partially glycosylated states weighing in between these two values.[2]
Angiotensinogen is also known as renin substrate. It is cleaved at the N-terminus by renin to result in angiotensin I, which will later be modified to become angiotensin II.[2][4] This peptide is 485 amino acids long, and 10 N-terminus amino acids are cleaved when renin acts on it.[2] The first 12 amino acids are the most important for activity.
- Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-...
Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels. In mice with a full body deficit of angiotensinogen, the effects observed were low newborn survival rate, stunted body weight gain, stunted growth, and abnormal renal development.[2]
Angiotensin III[edit]
- Asp | Arg-Val-Tyr-Ile-His-Pro-Phe
Angiotensin III has 40% of the pressor activity of angiotensin II, but 100% of the aldosterone-producing activity. Increases mean arterial pressure. It is a peptide that is formed by removing an amino acid from angiotensin II by aminopeptidase A.[5]
Activation of the AT2 receptor by angiotensin III triggers natriuresis, while AT2 activation via angiotensin II does not. This natriuretic response via angiotensin III occurs when the AT1 receptor is blocked.[6]
Angiotensin IV[edit]
- Arg | Val-Tyr-Ile-His-Pro-Phe
Angiotensin IV is a hexapeptide that, like angiotensin III, has some lesser activity. Angiotensin IV has a wide range of activities in the central nervous system.[7][8]
The exact identity of AT4 receptors has not been established. There is evidence that the AT4 receptor is insulin-regulated aminopeptidase (IRAP).[9] There is also evidence that angiotensin IV interacts with the HGF system through the c-Met receptor.[10][11]
Synthetic small molecule analogues of angiotensin IV with the ability to penetrate through blood brain barrier have been developed.[11]
The AT4 site may be involved in memory acquisition and recall, as well as blood flow regulation.[12] Angiotensin IV and its analogs may also benefit spatial memory tasks such as object recognition and avoidance (conditioned and passive avoidance).[13] Studies have also shown that the usual biological effects of angiotensin IV on the body are not affected by common AT2 receptor antagonists such as the hypertension medication Losartan.[13]
References[edit]
- ^ "Angiotensin | Hormone Health Network". www.hormone.org. Retrieved 2019-12-02.
- ^ a b c d e Lu, Hong; Cassis, Lisa A.; Kooi, Craig W. Vander; Daugherty, Alan (July 2016). "Structure and functions of angiotensinogen". Hypertension Research. 39 (7): 492–500. doi:10.1038/hr.2016.17. ISSN 1348-4214. PMC 4935807. PMID 26888118.
- ^ "AGT - Angiotensinogen precursor - Homo sapiens (Human) - AGT gene & protein". www.uniprot.org. Retrieved 2019-12-02.
- ^ a b Streatfeild-James, Rosa M. A.; Williamson, David; Pike, Robert N.; Tewksbury, Duane; Carrell, Robin W.; Coughlin, Paul B. (1998). "Angiotensinogen cleavage by renin: importance of a structurally constrained N-terminus". FEBS Letters. 436 (2): 267–270. doi:10.1016/S0014-5793(98)01145-4. ISSN 1873-3468. PMID 9781693. S2CID 29751589.
- ^ "Angiotensin III". PubChem. NIH. Retrieved 9 May 2019.
- ^ Padia, Shetal H.; Howell, Nancy L.; Siragy, Helmy M.; Carey, Robert M. (2006-03). "Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor–Blocked Rat". Hypertension. 47 (3): 537–544. doi:10.1161/01.HYP.0000196950.48596.21. ISSN 0194-911X.
{{cite journal}}: Check date values in:|date=(help) - ^ Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL (November 2004). "The angiotensin IV/AT4 receptor". Cellular and Molecular Life Sciences. 61 (21): 2728–37. doi:10.1007/s00018-004-4246-1. PMID 15549174.
- ^ Gard PR (December 2008). "Cognitive-enhancing effects of angiotensin IV". BMC Neuroscience. 9 Suppl 2: S15. doi:10.1186/1471-2202-9-S2-S15. PMC 2604899. PMID 19090988.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Albiston AL, McDowall SG, Matsacos D, Sim P, Clune E, Mustafa T, Lee J, Mendelsohn FA, Simpson RJ, Connolly LM, Chai SY (December 2001). "Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase". The Journal of Biological Chemistry. 276 (52): 48623–6. doi:10.1074/jbc.C100512200. PMID 11707427.
- ^ Wright JW, Harding JW (2015-01-01). "The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease". Journal of Alzheimer's Disease. 45 (4): 985–1000. doi:10.3233/JAD-142814. PMID 25649658.
- ^ a b Wright JW, Kawas LH, Harding JW (February 2015). "The development of small molecule angiotensin IV analogs to treat Alzheimer's and Parkinson's diseases". Progress in Neurobiology. 125: 26–46. doi:10.1016/j.pneurobio.2014.11.004. PMID 25455861. S2CID 41360989.
- ^ Wright JW, Krebs LT, Stobb JW, Harding JW (January 1995). "The angiotensin IV system: functional implications". Frontiers in Neuroendocrinology. 16 (1): 23–52. doi:10.1006/frne.1995.1002. PMID 7768321. S2CID 20552386.
- ^ a b Ho, Jean K.; Nation, Daniel A. (2018-09-01). "Cognitive benefits of angiotensin IV and angiotensin-(1–7): A systematic review of experimental studies". Neuroscience & Biobehavioral Reviews. 92: 209–225. doi:10.1016/j.neubiorev.2018.05.005. ISSN 0149-7634.