In four patients with
hypercholesterolemia (
type II hyperlipoproteinemia) and
xanthomatosis the decay of serum
cholesterol specific activity was followed for 53-63 wk after pulse labeling. Specific activity of biopsied
xanthoma cholesterol was measured four times in the course of the study. The
xanthoma specific activity curve crossed and thereafter remained above the serum specific activity curve. The average ratio of
xanthoma to serum specific activity was 4.7 at the end of the study. The final half-time of the
xanthoma decay curves was significantly greater (average: 200 days) than the slowest half-time of serum specific activity decay (average: 93 days). The data were analyzed by input-output analysis and yielded the following results. The average value for the total input rate of body
cholesterol (I(T)) (sum of dietary and biosynthesized
cholesterol) was 1.29 g/day. The average size of the rapidly miscible pool of
cholesterol (M(a)) was 55.7 g. and of the total exchangeable body mass of
cholesterol (M) 116.5 g. The average value of M - M(a) (remaining exchangeable mass of
cholesterol) was 60.8 g. The derived values for exchangeable masses of
cholesterol, in the present patients with marked
hypercholesterolemia, were significantly larger than in a group of patients with normal serum
lipids in previous studies. One of the four patients died of a sudden acute
myocardial infarction 53 wk after pulse labeling. Specific activity of aortic wall and
atheroma cholesterol was 3.12 times that of serum. The ratio was close to 2 for adipose tissue and spleen, and was slightly above 1 or was close to unity in most other organs studied, with the exception of brain which showed a ratio of 0.19.