N-Homocysteinyl-Proteins - Homocysteine in Protein Structure/Function and Human Disease - page 60

Table 5.1 Mouse genetic hyperhomocysteinemia: inactivation of folate (Mthfr, Pcft) or Hcy
(Cbs) metabolism genes increases N-Hcy-protein levels (Recalculated from [113])

Fold increase relative to wild-type littermates
N-Hcy-protein tHcy

Genotype (n) Plasma Liver Plasma Liver

Mthfr / (7) 6.3 1.4 8.6 1.1

Pcft / (4) 24.7 3.6 75.0 5.1

Cbs / (4)

8.1 58.3

Tg-S466L Cbs / (4) 12.6 60.9

Tg-I287T Cbs / (4)

10.4 11.3 143.2 75.7

Tg-hCBS Cbs / (4) 4.2 3.4 27.4 3.8

Table 5.2 Tissue levels of N-Hcy-protein and tHcy in Pcft / mice and wild-type Pcft +/+
littermates

Pcft
genotype

N-Hcy, pmol/
1 mg protein

N-Hcy, fold increase
in Pcft / vs. Pcft +/+

tHcy, pmol/
1 mg protein

tHcy, fold increase
in Pcft / vs. Pcft +/+ Organ

Brain a +/+ 47 10 1.2 113 13 1.2

/ 58 8 138 59

Heart b +/+ 112 22 2.8 166 33 4.3

/ 318 98 703 267

Lungs b +/+ 229 70 1.6 348 92 2.8

/ 362 113 969 524

Liver b,c

+/+ 87 32 3.7 299 92 5.1

/ 318 98 1,529 391

Kidney b

+/+ 126 49 1.8 499 194 2.2

/ 228 38 1,109 152

Plasma c +/+ 46 12 24.8 36 11 75.3

/ 1,132 264 2,696 566

Jakubowski and Perla-Kajan, unpublished data
a

p ¼ 0.14-0.22

b

0.005 for the differences in N-Hcy-protein or tHcy between Pcft / and Pcft +/+ mice
c Data from [113]

p <

and wild-type littermates (34.7 12.7 pmol/mg protein). In folate metabolism

deficiencies (Mthfr, Pcft), N-Hcy-protein levels increase much more in the plasma
than in the liver or other organs, while in Hcy metabolism deficiency (Cbs),
similar increases in N-Hcy-protein are observed in both the plasma and the liver
(Tables 5.1 and 5.2 ).
Protein N-homocysteinylation is reversibly modifiable by a diet (Table 5.3 ).
For example, plasma N-Hcy-protein increases 11.6-fold in mice fed a high-
methionine diet for 2 weeks, compared with animals fed a normal chow diet
[113]. The increase in N-Hcy-protein reflects 36-fold and 14-fold increases in
plasma tHcy and Hcy-thiolactone levels, respectively. After replacing the high-
methionine diet with a normal chow diet, plasma N-Hcy-protein decreases
sixfold after 2 weeks but remains twofold elevated compared with mice fed