User:Jcorelite/Angiotensin

Angiotensinogen
Angiotensinogen is an α-2-globulin synthesized in the liver and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides. It is a member of the serpin family of proteins, leading to another name: Serpin A8, 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. 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.

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. This peptide is 485 amino acids long, and 10 N-terminus amino acids are cleaved when renin acts on it. 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.

Angiotensin III

 * 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.

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.

Angiotensin IV

 * 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.

The exact identity of AT4 receptors has not been established. There is evidence that the AT4 receptor is insulin-regulated aminopeptidase (IRAP). There is also evidence that angiotensin IV interacts with the HGF system through the c-Met receptor.

Synthetic small molecule analogues of angiotensin IV with the ability to penetrate through blood brain barrier have been developed.

The AT4 site may be involved in memory acquisition and recall, as well as blood flow regulation. Angiotensin IV and its analogs may also benefit spatial memory tasks such as object recognition and avoidance (conditioned and passive avoidance). 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.