Synthesis and transsulfuration of homocysteine in blood.

Interest in total plasma homocysteine (homocyst[e]ine) as a risk factor for atherosclerosis is expanding. However, the origin of plasma homocyst(e)ine has not been defined. Our studies examined the metabolism of homocyst(e)ine by blood cells as a potential contributor to the homeostasis of homocyst(e)inemia. Incubation of blood for 24 hours at 37 degrees C produced a threefold increase in the level of plasma homocyst(e)ine. In samples of fractionated blood cells incubated in vitro, increases in total plasma homocysteine were limited to incubated erythrocyte fractions and were influenced by addition of methionine. Anticoagulants had no significant effect. Incubation of blood in the presence of methionine tagged with sulfur 35 demonstrated incorporation of label into homocysteine and transsulfuration products. Similar incubations of blood cell fractions suggested that synthesis of homocysteine occurred in erythrocytes, whereas leukocytes both synthesized and transsulfurated homocysteine. These findings demonstrated a possible interaction of different blood cells in the metabolism of methionine, as well as their potential role as a source of total plasma homocysteine in plasma.