biostudies-literatureKawaguchi RJapan Science and Technology AgencyJapan Society for the Promotion of ScienceBSR20253768https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905485biostudies-literatureUnknown46(1)Hyperhomocysteinemia is a risk factor of cardiovascular disease (CVD). High-density lipoprotein (HDL) plays an important role in anti-atherosclerosis, with its anti-atherogenic function attributed to HDL-associated proteins such as apolipoprotein A-I (apoA-I) and paraoxonase 1 (PON1). Homocysteine (Hcy) thiolactone modifies lysine residues in proteins, thereby altering their function. Although dysfunction of apoA-I and PON1 has been reported, the precise modification sites and underlying mechanisms have remained unclear. In this study, we aimed to identify Hcy-thiolactone modification sites on apoA-I and PON1. In addition, we sought to clarify the effects of Hcy-thiolactone on PON1 activity and its distribution. Modification sites were analyzed using MALDI-TOF MS. The effects of Hcy-thiolaBioscience reportsHomocysteine thiolactone affects paraoxonase 1 activity via altered paraoxonase 1 distribution on high-density lipoprotein particles.PMC1290548522K07466, 25K10657JPMJSP2120Kugii YOhkawa RHosoya SSuzuki NKawaguchi RSasaki TMiyakoshi TYoshimoto AfalseHomocysteine thiolactone affects paraoxonase 1 activity via altered paraoxonase 1 distribution on high-density lipoprotein particles.Hyperhomocysteinemia is a risk factor of cardiovascular disease (CVD). High-density lipoprotein (HDL) plays an important role in anti-atherosclerosis, with its anti-atherogenic function attributed to HDL-associated proteins such as apolipoprotein A-I (apoA-I) and paraoxonase 1 (PON1). Homocysteine (Hcy) thiolactone modifies lysine residues in proteins, thereby altering their function. Although dysfunction of apoA-I and PON1 has been reported, the precise modification sites and underlying mechanisms have remained unclear. In this study, we aimed to identify Hcy-thiolactone modification sites on apoA-I and PON1. In addition, we sought to clarify the effects of Hcy-thiolactone on PON1 activity and its distribution. Modification sites were analyzed using MALDI-TOF MS. The effects of Hcy-thiola2026-01-01T00:00:00Z2026 Jan2026-07-15T16:28:58.944Z2026-07-07T03:08:11.901ZS-EPMC129054854149656110.1042/BSR20253768