Renin, also known as angiotensinogenase, is a crucial enzyme produced and released primarily by the juxtaglomerular cells of the kidneys. It serves as the rate-limiting step in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure, fluid volume, and electrolyte balance. Understanding the substrate upon which renin acts is pivotal to grasp how this system functions.

What is the Substrate for Renin?

• The substrate for renin is angiotensinogen, a large plasma protein synthesized primarily by the liver and secreted into the bloodstream.

• Angiotensinogen is a member of the serpin family (serine protease inhibitors), although it itself does not inhibit proteases.

• Renin cleaves angiotensinogen at a specific bond between leucine and valine residues near its N-terminus, releasing the decapeptide angiotensin I.

• Angiotensin I is biologically inactive but serves as the precursor for angiotensin II, which is produced by angiotensin-converting enzyme (ACE) mainly in the lungs.

Renin’s Specific Action on Angiotensinogen

• Renin specifically recognizes and binds angiotensinogen, undergoing a conformational change that allows precise cleavage.

• This proteolytic cleavage initiates a cascade vital for cardiovascular and renal regulation of blood pressure and electrolyte homeostasis.

• Renin’s activity depends on availability of angiotensinogen, blood flow, sympathetic stimulation, and sodium levels sensed by the kidney.pmc.ncbi.nlm.nih+2

Why Other Options Are Incorrect

• Angiotensin I (option 2) is the product formed after renin acts; it is not the substrate for renin.

• Angiotensin II (option 3) is formed from angiotensin I by ACE; it does not serve as a substrate for renin.

• Renin itself (option 4) is the enzyme, not a substrate.

Importance in Physiology

• The renin-angiotensin system modulates vasoconstriction, aldosterone secretion, and sodium retention.

• Disruption in renin or angiotensinogen levels can lead to disorders like hypertension or hypotension.

• Therapeutic agents targeting this system include ACE inhibitors and angiotensin receptor blockers.

Conclusion

The correct and natural substrate for renin (angiotensinogenase) is angiotensinogen.

Answer: (1) Angiotensinogen