| Identification | Back Directory | [Name]
RENNIN | [CAS]
9015-94-5 | [Synonyms]
RENIN
RENNET
RENNIN
MUCORPEPSIN
RENIN HUMAN
EC 3.4.23.23
Native Human Renin
RENIN, HUMAN KIDNEY
RENIN, HUMAN PLASMA
RenninExCalfStomach
renin from hog kidney
RENIN, HUMAN RECOMBINANT
renin from porcine kidney
Angiotensin forming enzyme
Renin from Mouse, recombinant
Renin from Human, Recombinant
RENIN FROM HOG KIDNEY, LYOPH., ~0.01 U/MG, 250 UG*
Angiotensin forming enzyme, Renin from hog kidney | [EINECS(EC#)]
232-796-2 | [MDL Number]
MFCD00132171 |
| Questions And Answer | Back Directory | [Properties]
Mr. 38 kDa. Renin has high specificity on AGT and
cleaves Ang I from AGT. The cleavage specificity is determined by the [HPF]-domain on Ang I.
Renin recognizes this signature domain and cleaves the
peptide bond at two aa residues after the domain. The
[HPF]-domain is highly conserved among vertebrates
(see Angiotensin II), indicating that similar functional
constraints could be present in other vertebrate renins.
Renin can be activated by proteolysis, acidic pH, and
low temperature. | [Gene, mRNA, and mRNA]
REN1 is located at chromosome 1q32.1 in humans.
Renin is synthesized as an inactive form called prorenin
but recent studies indicated that prorenin can bind to
the renin receptor and activate the cleavage site reversibly
by changing the conformation of the prosegment. REN1 is synthesized mainly by the kidney but mRNA
is also found in many other tissues, including the heart,
brain, and adrenal glands. | [Synthesis and release]
The macula densa, in response to the change in the Na
concentration in the distal tubules, signals the juxtaglomerular cells to release renin. Renin is stored in granules
and the secretion is stimulated by the β-adrenergic
response and cAMP augmentation. The release of active
renin from the kidney is inhibited by increased arterial
pressure or Ang II, and an increased intracellular Ca concentration. This is in contrast to the other secretory cells,
in which an increase in intracellular calcium usually
enhances the depletion of secretory granules. Thus, this
is often called the calcium paradox. The regulatory elements of the promoter of the renin gene were termed
the “renin enhancer.” This was later found to be a compound regulatory element with several stimulatory and
inhibitory activities. In the renin enhancer, cAMP
response elements have been identified. Besides transcriptional regulation, a posttranslational regulation at
the untranslated region (a 200 bp segment beyond the
coding region) was also known, where the mRNA stability can be enhanced by cAMP stimulation. | [Receptors]
The renin receptor (ATP6AP2) binds to both prorenin
and renin. The renin receptor gene is located on chromosome Xp11. in humans. The major known function is
that the binding increases the catalytic activity of renin
on AGT by 5–10 fold: the Km for AGT (in the absence
of the renin receptor) is 1μM and the Km of the
membrane-bound renin receptor complex is 0.15μM.
The renin receptor is abundantly expressed in the heart,
brain, and placenta, and lower expressions are found in
the kidney and liver. In the brain, the renin receptor is
expressed in the subfornical organ, paraventricular
nucleus, supraoptic nucleus, tractus solitaries nucleus,
and rostral ventrolateral medulla, which are likely
involved in the regulation of cardiovascular and volume
regulation. Global knockout of the renin receptor is
embryonically lethal. Genome data also suggest that
the orthologous renin receptor is present in other vertebrates, including teleosts and tetrapods. | [Antagonist]
Aliskiren is the first in a new class of orally active, nonpeptide, low-molecular-weight renin inhibitors. It is a
transition-state mimetic with favorable physicochemical
properties, including high aqueous solubility
(350mg/mL at pH 7.4) and high hydrophilicity (log
Poct/water=2.45 at pH 7.4), which are important properties for oral bioavailability. Aliskiren is designed
through a combination of molecular modeling techniques
and crystal structure elucidation, and it effectively
reduces the blood pressure as a monotherapy as well in
combination therapy. | [Biological functions]
Renin is the rate-limiting enzyme that initiates the cascade generating the angiotensin peptides that regulate
blood pressure, cell growth, apoptosis, and electrolyte
balance. Renin is a hormone that ultimately integrates
cardiovascular and renal function in the control of blood
pressure as well as salt and volume homeostasis. Prorenin is activated by proteolytic enzymes such as trypsin and kallikrein. Acid treatment (optimal pH at 3.3) and
low temperature fully or partially (~15%) activate prorenin. The binding of prorenin to the renin receptor changes
the conformation of the prosegment to expose the active
site to activate the enzyme. |
| Chemical Properties | Back Directory | [storage temp. ]
−20°C
| [form ]
powder
| [color ]
slightly brown
| [Merck ]
13,8218 | [Uses]
Rennin is a milk coagulant that is an enzyme obtained from the abo-
masum portion of the stomach of suckling mammals. it is most
active at ph 3.8. one part purified rennin will coagulate more than
five million parts of milk. the commercial extract of rennin is termed
rennet. it is used to coagulate milk in making cheese, junket, and
custard. see rennet. |
| Hazard Information | Back Directory | [Description]
Renin is the rate-limiting enzyme for the initiation of the
cascade of the renin-angiotensin system. Plasma renin activity is a marker for hypertension. This is a drug target for
hypertension and renal disease. In the late 18th century, renin was discovered based on the
observation that the injection of saline extracts from fresh rabbit kidneys into other rabbits increased arterial blood
pressure. | [Definition]
An enzyme secreted by cellslining the stomach in mammals thatis responsible for clotting milk. Itacts on a soluble milk protein (caseinogen),which it converts to theinsoluble form casein. This ensuresthat milk remains in the stomachlong enough to be acted on by protein-digesting enzymes. | [Biological Functions]
Renin is an enzyme that is synthesized and stored in the
renal juxtaglomerular apparatus and that catalyzes the
formation of a decapeptide, angiotensin I, from a
plasma protein substrate. Renin has a narrow substrate
specificity that is limited to a single peptide bond in angiotensinogen,
a precursor of angiotensin I. Renin is
considered to control the rate-limiting step in the ultimate
production of angiotensin II. Control of renin secretion
by the juxtaglomerular apparatus is important
in determining the plasma renin concentration.
Three generally accepted mechanisms are involved
in the regulation of renin secretion. The first
depends on renal afferent arterioles that act as stretch
receptors or baroreceptors. Increased intravascular
pressure and increased volume in the afferent arteriole
inhibits the release of renin. The second mechanism is
the result of changes in the amount of filtered sodium
that reaches the macula densa of the distal tubule.
Plasma renin activity correlates inversely with dietary
sodium intake. The third renin secretory control mechanism
is neurogenic and involves the dense sympathetic
innervation of the juxtaglomerular cells in the afferent
arteriole; renin release is increased following activation
of 1-adrenoceptors by the neurotransmitter norepinephrine.
Angiotensin II, the primary end product of the
renin–angiotensin system, acts on the juxtaglomerular
cells to inhibit the release of renin; this process is therefore
a negative feedback mechanism. The half-life of
renin in the circulation is 10 to 30 minutes, with inactivation
occurring primarily in the liver. Small amounts of
renin are eliminated by the kidneys. Pure human renin has been used to develop specific inhibitors of the enzyme.
Low-molecular-weight orally effective renin inhibitors
are under development. | [Clinical Use]
Renin inhibitors can be used for the treatment of
hypertension. In current medical practice, PRA is the
indicator of RAS overactivity and is more commonly treated using either ACE blockers and/or AT1 blockers
rather than a direct oral renin inhibitor. ACE inhibitors
and/or AT1 blockers are also part of the standard treatment after a heart attack. The diagnosis of kidney cancer
includes a juxtaglomerular cell tumor (reninoma), Wilms’
tumor, and renal cell carcinoma, all of which may produce renin and lead to hypertension in patients. | [Structure and conformation]
Renin is a highly specific endopeptidase whose only
known function is to generate angiotensin I (Ang I) from
angiotensinogen (AGT), initiating a cascade of reactions
that produces elevated blood pressure and increased
sodium retention by the kidney. REN1 is a protein coding gene with 406 aa residues in
humans; it forms an aspartyl protease. |
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