Bradykinin potentiating peptide

Question 1

structure of BPP

Answer 1

5-13 amino acid resides, proline-rich peptide with cyclized form of glutamate at N-terminus

Question 2

target of BPP

Answer 2

ACE = angiotensin-converting enzyme ; trans-membrane metallopeptidase with 2 active sites in N and C domain

Question 3

AngII

Answer 3

vasoconstriction and increase aldosterone = which increases Na+ retention = increase blood volume

Question 4

MOA of bj-bpp

Answer 4

binding to ACE prevents the conversion of angI to angII and inhibits the inactivation of bradykinin

Question 5

Types of bpp

Answer 5

Bj-BPP-9a , 10c, 5a, 12b

Question 6

Bj-BPP-9a

Answer 6

discovery of 9a led to the creation of ACE inhibitor drug = captopril

Question 7

Bj-BPP-10c

Answer 7

most selective inhibitor of C-domain of ACE ; most potent in eliciting hypotensive effects ; its main target is AsS (argininosuccinate synthase) ; enhance arginine production

Question 8

How does AsS binding cause anti-hypertension effects?

Answer 8

10c binding to the AsS leads to the activation of enzymatic activity of AsS, increasing NO produced when L-arginine is converted to L-citrulline.

Question 9

How does NO production lead to hypotensive effects

Answer 9

endothelial cells produce NO ; NO diffuse to the smooth muscle cells in the blood vessels ; cGMP produced and relax the smooth muscle ; Ca2+ levels decrease as well, leading to relaxation of smooth muscle

Question 10

function of AsS in urea cycle

Answer 10

AsS is part of the urea cycle in the liver and of the arginine-citulline cycle. The cycle provide the main source of arginine and NO in the renal and endothelial cells respectively. in the endothelial cells, the arginine-citrulline cycle + NOS ensures supply of NO

Question 11

Bj-BPP-5a

Answer 11

not as potent as the others in terms of inhibiting ACE activity but does have high levels of bradykinin potentiating activity - through NO-dependent mechanism :
-depend on M1 AChRs muscarinic subtype
-bradykinin beta 2 receptor activation
(both contribute to vasodilation induced by 5a)
-presence of NOS inhibitor (blocked vasodilation by 5a

Question 12

toxin to therapeutics

Answer 12

SARS-CoV2 binds to ACE2 inhibiting it (therefore inhibiting the conversion of ATII to AT(1-7)) ;
When ACE2 is inhibited, bradykinin-1 receptor is activated to promote vasodilation so that immune cells can reach to the site of infection faster ;
but SARS-CoV 2 also limits the activation of bradykinin therefore affecting vasodilation ;
The renin-angiotensin system (RAS) and kinin-kallikrein system (KKS) are tightly linked
thus 10c is the solution as it targets both RAS and KKS by potentiating BPP production while inhibiting ACE, reducing ACE in body