Mammalian cells cannot use plant sterols. Normally, plant sterols are poorly absorbed from the gastrointestinal tract; fewer than 5% of plant sterols are absorbed compared to approximately 40% of cholesterol absorbed. The liver preferentially excretes plant sterols over cholesterol. Dietary sterols have recently been shown to passively enter intestinal cells, and subsequently the vast majority are pumped back into the gut lumen by ATP-binding cassette transporter (ABC transporter) proteins.<unk>  is inherited as a rare autosomal recessive condition. It has been shown to result from mutations in either of two adjacent and oppositely oriented genes (ABCG5 and ABCG8) located in chromosome 2 in band 2p21 and encode for ABC transporter proteins named sterolin-1 and sterolin-2, respectively. Thus, the active pumping back into the intestine of passively absorbed plant sterols is disrupted, and hepatic secretion of the resultant accumulation of these sterols is decreased. The ability of the liver to preferentially excrete plant sterols into the bile is apparently impaired. While bile acid synthesis remains the same as in healthy people, the total excretion of sterols in the bile is reportedly less than 50% in subjects with<unk>  compared to control subjects. The mechanism for decreased hepatic secretion is unknown. Patients have markedly reduced whole-body cholesterol biosynthesis associated with suppressed hepatic, ileal, and mononuclear leukocyte hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-controlling enzyme in the cholesterol biosynthetic pathway. Whether or not the down-regulation is due to accumulated sitosterol is still debatable, but most recent data indicate that secondary effects of unknown regulators other than sitosterol can lead to reduced HMG-CoA reductase activity in the disease. This is coupled with significantly increased low-density lipoprotein (LDL) receptor expression.
Sitosterolemia
Dehydration
Hypoaldosteronism
Pseudohypoaldosteronism
Stress hyperglycemia
Acromegaly
Isotonic hyponatremia
Apparent mineralocorticoid excess syndrome