The plasma level of homocysteine (Hcy) and its oxidized products, i.e.
, plasma total Hcy (tHcy), is a function of the influx rate of Hey to
plasma and the plasma tHcy clearance. In vitro experiments show that p
roliferating cells usually export more Hcy than stationary cells and t
hat the Hcy export increases in response to high methionine, low folat
e or low cobalamin level, and to agents interfering with Hcy remethyla
tion. Comparison between various cell types suggests that hepatocytes
have a unique ability to increase the Hcy export in response to extrac
ellular methionine, probably due to its capacity to form adenosylmethi
onine. Some but not all cell types have an ability to use extracellula
r Hey as a methionine source. Clearance studies in healthy subjects in
dicate that about 1.2 mmol Hey is supplied from the cells to plasma pe
r 24 h, which is only about 5-10% of total Hcy formed. Comparison of a
rea under the curves after administration of Hcy and methionine shows
that about 10% of the methionine administered is released to plasma as
Hcy. Notably, only a few percent of Hey from plasma is excreted uncha
nged in the urine, and this shows that most tHcy in plasma is metaboli
zed. Folate or cobalamin deficient patients have normal plasma tHcy cl
earance, which suggests that their elevated tHcy level is due to incre
ased Hey export from tissues into the plasma compartment. In contrast,
the hyperhomocysteinemia in renal failure is accounted for by a marke
d reduction in tHcy clearance, suggesting an important role of kidney
in elimination of Hcy from plasma.