TY - JOUR
T1 - The possible role of a bacterial aspartate β-decarboxylase in the biosynthesis of alamandine
AU - Jha, Shalinee
AU - Speth, Robert C.
AU - Macheroux, Peter
PY - 2020/11
Y1 - 2020/11
N2 - The understanding of the renin-angiotensin system (RAS) has significantly expanded over the last two decades. The elucidation of angiotensin-converting enzyme 2 (ACE2) that converts angiotensin (Ang) II into Ang (1–7) led to the discovery of the cardio-protective axis of the RAS. In addition, novel components of the system, Angiotensin A (Ang A) and alamandine have been identified. Like Ang (1–7), alamandine is a vasodilator and can counteract the effects of Ang II by increasing nitric oxide release from the endothelium and decreasing nicotinamide adenine dinucleotide phosphate oxidase (NADPH)-related superoxide production. Theoretically, alamandine can be derived from Ang (1–7) by decarboxylation of the N-terminal aspartic acid residue to alanine, but the enzyme responsible for this is still unknown. To date, no human or mammalian enzyme with the assigned decarboxylase activity has been identified. However, several bacterial enzymes capable of converting aspartate to alanine have been reported. Therefore, we hypothesize that a bacterial enzyme, most likely present in the microbiome of the gastrointestinal tract, the heart, or systemic circulation could metabolize Ang II, and/or Ang 1–7, to Ang A and alamandine, respectively, in mammals
AB - The understanding of the renin-angiotensin system (RAS) has significantly expanded over the last two decades. The elucidation of angiotensin-converting enzyme 2 (ACE2) that converts angiotensin (Ang) II into Ang (1–7) led to the discovery of the cardio-protective axis of the RAS. In addition, novel components of the system, Angiotensin A (Ang A) and alamandine have been identified. Like Ang (1–7), alamandine is a vasodilator and can counteract the effects of Ang II by increasing nitric oxide release from the endothelium and decreasing nicotinamide adenine dinucleotide phosphate oxidase (NADPH)-related superoxide production. Theoretically, alamandine can be derived from Ang (1–7) by decarboxylation of the N-terminal aspartic acid residue to alanine, but the enzyme responsible for this is still unknown. To date, no human or mammalian enzyme with the assigned decarboxylase activity has been identified. However, several bacterial enzymes capable of converting aspartate to alanine have been reported. Therefore, we hypothesize that a bacterial enzyme, most likely present in the microbiome of the gastrointestinal tract, the heart, or systemic circulation could metabolize Ang II, and/or Ang 1–7, to Ang A and alamandine, respectively, in mammals
KW - Alamandine
KW - Aspartate β-decarboxylase
KW - Gut bacteria
KW - Renin-angiotensin system
UR - http://www.scopus.com/inward/record.url?scp=85087033669&partnerID=8YFLogxK
U2 - 10.1016/j.mehy.2020.110038
DO - 10.1016/j.mehy.2020.110038
M3 - Article
SN - 1532-2777
VL - 144
JO - Medical Hypotheses
JF - Medical Hypotheses
M1 - 110038
ER -