A mutant form of polypeptide hormone angiotensin II has the amino acid compositi

Question

A mutant form of polypeptide hormone angiotensin II has the amino acid composition
(Asp, Arg, Ile, Met, Phe, Pro, Tyr, Val)
The following observations are made:
Trypsin yields a dipeptide containing Asp and Arg, and a hexapeptide with all the rest.
Cyanogen bromide cleavage yields a dipeptide containing Phe and Pro, and a hexapeptide containing all the others.
Chymotrypsin cleaves the hormone into two tetrapeptides, of composition
(Asp, Arg, Tyr, Val) and (Ile, Met, Phe, Pro)
The dipeptide of composition (Pro, Phe) cannot be cleaved by either chymotrypsin or carboxypeptidase.

Part A

What is the sequence of angiotensin II?

The sequence must be Asp-Arg-Tyr-Val-Ile-Met-Pro-Phe ( two of these are misplaced which two are there?

Explanation / Answer

Angiotensinogen-

Angiotensinogen is an -2-globulin produced constitutively and released into the circulation mainly by the liver. It is a member of the serpin family, although it is not known to inhibit other enzymes, unlike most serpins. Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.

Angiotensinogen is also known as renin substrate. Human angiotensinogen is 453 amino acids long, but other species have angiotensinogen of varying sizes. The first 12 amino acids are the most important for activity.

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-...

Angiotensin II-

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe | His-Leu

Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells and kidney epithelial cells). ACE found in other tissues of the body has no physiological role (ACE has a high density in the lung, but activation here promotes no vasoconstriction, angiotensin II is below physiological levels of action).[citation needed] Angiotensin II acts as anendocrine, autocrine/paracrine, and intracrine hormone.

ACE is a target for inactivation by ACE inhibitor drugs, which decrease the rate of Angiotensin II production. Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates an IP3-dependent mechanism leading to a rise in intracellular calcium levels and ultimately causing contraction). In addition, angiotensin II acts at the Na/H exchanger in the proximal tubules of the kidney to stimulate Na reabsorption and H excretion which is coupled to bicarbonate reabsorption. This ultimately results in an increase in blood volume, pressure, and pH.[4] Hence, ACE inhibitors are major anti-hypertensive drugs.

Other cleavage products of ACE, seven or 9 amino acids long, are also known; they have differential affinity for angiotensin receptors, although their exact role is still unclear. The action of AII itself is targeted by angiotensin II receptor antagonists, which directly block angiotensin II AT1 receptors.

Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. It has a half-life in circulation of around 30 seconds, whereas, in tissue, it may be as long as 15–30 minutes.

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