An Overview of Homocysteine Metabolism - Homocysteine in Protein Structure/Function and Human Disease - page 10

in mouse liver are 50-160 pmol/mg protein and increase 4- and 12-fold in Pcft /
and Cbs / animals [113].

2.1.5 N

ε -Homocysteinyl-Lysine

The isopeptide Nε -Hcy-Lys, discovered in vitro as a product of a facile reaction of

Hcy-thiolactone with lysine [73], forms in vivo during proteolytic turnover of
N-Hcy-protein [72]. Nε-Hcy-Lys is undetectable in normal human plasma
( M in patients with renal disease and

CBS deficiency, respectively. In normal mouse plasma, Nε

0.1 μ M) and increases to 0.17 and 0.42 μ

<

-Hcy-Lys level is 0.4 μ M

(Table 2.1 ) and increase up to tenfold in hyperhomocysteinemic animals.

2.1.6 S -Adenosylhomocysteine

AdoHcy, an immediate precursor of Hcy (Fig. 1.1 ), occurs in human cells at
micromolar concentrations, while in plasma, it is present at nanomolar
concentrations (Table 2.1 ) [116, 117]. AdoHcy concentrations are 33-fold higher
in human urine than in plasma, consistent with its significant fractional excretion
(39 %) [117].

2.1.7 Cystathionine

Normal human plasma level of cystathionine, an intermediate in the transsul-
furation pathway converting Hcy to Cys, is 126 nM. Cystathionine concentrations
are much higher in urine, reaching millimolar range (Table 2.1 ). The urinary
clearance of cystathionine is 50.9 % of the clearance of creatinine [98]. In mice,
normal plasma cystathionine concentration is 2,479 nM [118], 20-fold higher than
in normal human plasma.

2.1.8 Homocysteic Acid and Homocysteine Sulfinic Acid

Other oxidized Hcy metabolites have been reported in humans and experimental
animals: homocysteine sulfinic acid (HSA) and homocysteic acid (HCA). However,
the mechanism of biological formation of HSA and HCA is not known. Normal
human plasma concentration is 677 38 nM for HCA

(Table 2.1 ) [99]. Elevation of Hcy and HCA occurs in cerebrospinal fluid of

210 nM for HSA and 186