1. Introduction

The kallikreins are a group of serine proteases known as kininogens, which act on plasma α2-globulins to release kinins such as bradykinin. Bradykinin is the most potent vasodilator substance known.

The kallikrein–kinin system consists of proteins present in blood and other body fluids such as lymph, urine, saliva, pancreatic juices. In the blood they play a role in coagulation, blood pressure control, and inflammation.

2. Biochemistry and Physiology

Two classes of kallikreins have been identified: (a) those present in plasma and (b) those present in organs, including the kidney, salivary glands, and pancreas. The plasma kallikreins have molecular weights of ~70,000 and ~110,000 Da. All of the kallikreins are serine pro teases. There are 14 kallikreins.

The plasma kallikrein is normally found as a proenzyme termed prekallikrein. Prekallikrein is activated to kallikrein by one of the blood-clotting factors, factor XII, or Hageman factor. In turn, the Hageman factor is activated by the plasma kallikrein (see Figure 1C). The kallikreins utilize their protease activity to release peptide kinins from their precursor substrate forms.

Fig1. Fundamentals of blood pressure regulation by integrated actions of the peptide hormones renin, and angiotensin II, and the steroid hormone aldosterone. (A) A flowchart of 14 sequential steps that becomes activated starting with an acute decrease either in blood volume and/or blood pressure that is detected by the kidney, resulting in the release of the enzyme protease, renin, which functions as a hormone. Renin, also known as angiotensinogenase, has 406 amino acids while the functional mature renin has 340 amino acids (~37 kDa). Renin is secreted by the granular cells associated with the glomerulus in response to a drop in blood pressure and/or a decrease in Na+ concentration. Renin’s substrate is the blood protein, α2-globulin (57 kDa), that has been secreted by the liver and then localized within the capillaries of the lungs. This is described in steps #4 to #7 of panel 4A. The hormone angiotensin II is an octapeptide produced by the Angiotensin Converting Enzyme (ACE; step #8) acting on the precursor, angiotensin I. Angiotensin II is a hormone that acts on the zona glomerulosa of the adrenal cortex where it stimulates the production and secretion of the steroid hormone, aldosterone, which binds to its receptor in the kidneys . Then in steps #11 to #14, angiotensin II stimulates the release of the steroid hormone aldosterone from the adrenal cortex (zona glomerulosa) which then binds to its receptor localized in the kidney’s collecting duct where it increases the reabsorption of both Na+ and water and, also, increases secretion of H+ and K+ into the urine, thus leading to an increased blood volume, which increases blood pressure until it has returned to normal. (B) Amino acid sequence of the hormone angiotensin II and two precursor peptides. Panel 4B presents the following: (i) the 13 amino acid pro-hormone portion cleaved off angiotensinogen which has 453 amino acids; (ii) the 10 amino acid peptide sequence of angiotensin I (not a hormone); and (iii) the 8 amino acid peptide sequence of the active hormone, angiotensin II. (C) A schematic illustration of the sources of production of the peptide hormones renin, angiotensin II, and bradykinin and the steroid hormone, aldosterone. There are three important protein sources: (a) the plasma α2-globulin (57 kDa) which is the substrate for (b) the enzyme, renin (42 kDa), that is secreted by the kidney’s juxtaglomerular cells based on changes in renal arterial pressure; and (c) the prekallikrein (86 kDa; see upper right blue rectangle), that is converted by the activated Hagemen Factor (also known as blood coagulation factor XI; 80 kDa) that cleaves off an 85 kDa portion of prekallikrein. When the enzyme kininase II serine protease becomes available, it inactivates bradykinin by removing one or two amino acids from the active bradykinin (a potent vasodilator). The same kininase II enzyme (angiotensin converting enzyme, ACE) also can cleave a 2 amino acid peptide from angiotensin I, which then generates angiotensin II, which is a potent vasoconstrictor. The same angiotensin II, besides being a potent vasoconstrictor, also is a stimulating agent for the biosynthesis of aldosterone in the zona glomerulosa of the adrenal cortex.

The receptors for bradykinin are a group of G-protein coupled proteins that, when activated, increase the cytosol Ca2+ concentration. The bradykinin receptor is present on the human BDKRB1 gene. The principal kinin is a nonapeptide named bradykinin. It has the following amino acid sequence: Arg Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg. The bradykinin receptor, which is principally associated with endothelial cells, has been cloned and found to belong to the seven-transmembrane G-protein-coupled receptor superfamily.

It is noteworthy that the principal mode of inactivation of bradykinin is the removal from the COOH terminal of a dipeptide by an enzyme termed kininase II; see Figure 1C. The enzymatic activities of kininase II and the enzymatic activities of angiotensin I converting enzyme (ACE) have shown them to be the same protein. Thus, ACE, which generates the potent vasoconstrictor, angiotensin II, inactivates the vasodilator bradykinin.

اخر الاخبار

اخبار العتبة العباسية المقدسة

استعدادًا لانطلاق الفعاليات.. وصول المشاركات في مسابقة بصائر العلم الوطنية إلى مجمع الشيخ الكليني

قسم الشؤون الدينية يستذكر فضائل يوم دحو الأرض عبر محاضراته اليومية

عبر منافذ العتبة العباسية المقدسة.. ممثّلية مواكب محافظتي ديالى وذي قار تشارك بحملة التبرّع للشعبين الإيراني واللبناني

لتوسيعِ آفاقِ الإفادةِ من محتواها.. مركز الشيخ الأنصاري يحدّث الموقع الإلكترونيّ لمجلّة الخزانة

المزيد

الآخبار الصحية

خبير يكشف 5 حقائق طبية صادمة وغير معروفة

ليس الأسود ولا الحيتان.. "كائن صغير" هو أخطر قاتل للبشر!

بارقة أمل لمرضى "الإيدز".. علاج خلوي ينجح في كبح الفيروس

ظاهرة مقلقة تتوسع.. "المستنشقات" خطر صامت يهدد المراهقين

المزيد

الآخبار التكنلوجية

اكتشاف مادة في الثوم تحسن قوة العضلات وتبطئ شيخوختها

تطور الحياة على الأرض المبكرة اعتمد على معدن نادر

باحثون صينيون يطوّرون بطارية مائية قد تعمل 300 عام

الذكاء الاصطناعي..هل يصبح متهما جنائيا في الجرائم والانتحار؟

المزيد

مواضيع ذات صلة

Biological Actions of NO

Biological Actions of Endothelins

Red Blood Cell Enzymopathies- Metabolic Pathways

Hemoglobins with Decreased Oxygen Affinity

Chemistry, Biosynthesis, and Secretion of Nitric Oxide System

Chemistry, Biosynthesis, and Secretion of Endothelins

Chemistry, Biosynthesis, and Secretion of ANP

Hemoglobins with Increased Oxygen Affinity

Specific Enzymes are Associated with Compartments Separated by the Mitochondrial Membranes

ATP Acts as the “Energy Currency” of The Cell

Living Organisms Package Transition Metals Within Organometallic Complexes

Androgen Biosynthesis