An Overview of Homocysteine Metabolism - Homocysteine in Protein Structure/Function and Human Disease - page 8

Table 2.1 Concentrations of Hcy metabolites in normal human and mouse plasma and urine
Hcy metabolite Concentration (nM) in human Concentration (nM) in mouse

Plasma Urine Plasma Urine

tHcy 12,000 2,500 3,000 45,000

Hcy 250

Hcy-S-S-Hcy + Hcy-S-S-Cys 1,940

S-Hcy-protein 9,810

Hcy-thiolactone 0.2 168 3.7 136

N-Hcy-protein 490 1,900

Nε -Hcy-Lys 100 100 400 100

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AdoHcy 15 490

Homocysteic acid 186

Homocysteine sulfinic acid 677

Cystathionine 126 350-49,900 2,479

Concentration values are from references discussed in the text

2.1.1 “Total Homocysteine”

The sum of free thiol (reduced) and disulfide-bound Hcy (oxidized) species,
obtained by the treatment of a sample with a reducing agent, is called “total Hcy”
(tHcy) and serves as a plasma marker in clinical studies of relationships between
Hcy metabolism and human disease [102]. Unfortunately, the term “total Hcy” is a
misnomer because it does not include a host of important Hcy congeners (discussed
in the following sections). Normal tHcy levels of about 10 μ M increase to several

hundred M in genetic deficiencies in Hcy, folate, or vitamin B 12 metabolism, both

in mice and humans. In normal human plasma, S-Hcy-protein comprises ~80 % of
tHcy, homocystine Hcy-S-S-Hcy and homocysteine-cysteine mixed disulfide Hcy-
S-S-Cys comprise 20 %, while free thiol Hcy comprises just ~1 % of tHcy
(Table 2.1 ) [87].
In healthy humans, tHcy concentration in plasma (~10

μ

μ M) is ~twofold higher

than in urine [95]. In mice, however, plasma tHcy (3.5 M) is 15-fold lower than

urinary tHcy (Table 2.1 ) [93]. While in humans urinary tHcy clearance is insignifi-
cant (~1 %), in mice a significant fraction of tHcy (~38 %) is eliminated by urinary
excretion [93]. It should be noted, however, that because the reduction of the
disulfide bonds in the commonly used tHcy assays is carried out at alkaline pH,
one of them—Hcy-thiolactone—most likely contributes to the tHcy pool.

μ

2.1.2 S -Homocysteinyl-Protein

Plasma protein S-linked Hcy is carried on albumin [103] and γ -globulin [79] and in

smaller quantities on transthyretin [104, 105], α 1 -acid glycoprotein, and high-

density lipoprotein (HDL) [106]. Each of those proteins, except ApoA1 in HDL,