Identifying a role for the interaction of homocysteine and copper in promoting cardiovascular-related damage

Homocysteine and copper ions: is their interaction responsible for cardiovascular-related damage?

“…The authors observed an intramolecular hydrogen atom (H) transfer resulting in α-amino carbon-centered radical, which is known to promote biological damage (see Refs. in Gupta et al 2021 ). Critical concerns in the experiments by Gupta et al ( 2021 ) are the drastic experimental conditions, i.e., reflux for 2 min and the use of very high concentrations of l -homocysteine (5 mM) and of CuCl 2 (5 mM).…”

“…in Gupta et al 2021 ). Critical concerns in the experiments by Gupta et al ( 2021 ) are the drastic experimental conditions, i.e., reflux for 2 min and the use of very high concentrations of l -homocysteine (5 mM) and of CuCl 2 (5 mM). Such concentrations are almost three orders of magnitude higher than pathophysiological and even toxic concentrations of l -homocysteine (Mansoor et al 1992 ) and CuCl 2 .…”

“…I read with great interest the paper by Gupta et al “Identifying a role for the interaction of homocysteine and copper in promoting cardiovascular-related damage”, which was recently published in Amino Acids (Gupta et al 2021 ). Homocysteine, i.e., specifically plasma total homocysteine, is considered to be associated with oxidative stress and to be an independent risk factor in over 100 conditions, especially including diseases associated with the cardiovascular and central nervous systems, and to be a guide for the prevention of disease (Smith and Refsum 2021 ).…”

“…Such a dose would lead to blood Cu 2+ concentrations of about 50 mM in laboratory (200 g weighing) rats. Also, no demonstration of an l -homocysteine/CuCl 2 -specific biological damage was reported, except for the observation of a C α reactive radical (Gupta et al 2021 ). It is worth mentioning that Cu 2+ ions can bind to circulating proteins, such as albumin and enzymes, such as ceruloplasmin, the most abundant carrier of Cu 2+ ions in the human circulation.…”

“…Free L-homocysteine and free Cu 2+ ions are unlikely to play a major role in cardiovascular disease, even not in severe hyper-homocysteinemia (> 15 µM), by inducing α-amino carbon-centered radical formation from l -homocysteine (Gupta et al 2021 ). Reported observations obtained using high concentrations of l -homocysteine and of potentially important factors such as Cu 2+ ions are misleading and presumably not related to homocysteine’s biology.…”