dolichols and Osteoporosis

The case report of a family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive-compulsive disorder (OCD), major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa, and healthy aging with longevity is described. The family members had hyposexual behavior and less tendency toward spirituality. They did not have insomnia, but they did display tendency toward increased somnolence. No addictive behavior was observed. The family demonstrated a high level of bonding and affectionate behavior, and they were less creative, with an average intelligence quotient (IQ). There was a total absence of vascular thrombosis, systemic neoplasms and neuronal degeneration in the indexed family. All members of the indexed family were left hemispheric dominant. The levels of serum digoxin, HMG-CoA reductase activity, and dolichol were found to be decreased in the members of the indexed family, with a corresponding increase in red blood cell (RBC) Na(+)-K+ ATPase activity, serum ubiquinone and magnesium levels. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in the serum. The total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, activity of glycosaminoglycans (GAG) degrading enzymes, and glycohydrolases were decreased in the serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased, while the cholesterol: phospholipid ratio of the membrane decreased. The activity of free radical scavenging enzymes were increased, while the concentration of free radicals decreased significantly. The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed.

Topics: Body Mass Index; Brain Chemistry; Depressive Disorder, Major; Digoxin; Dolichols; Dominance, Cerebral; Erythrocytes; Family Health; Female; Glycosaminoglycans; Humans; Hydroxymethylglutaryl CoA Reductases; Hypertension; Hypothalamic Diseases; Male; Obsessive-Compulsive Disorder; Osteoporosis; Respiration Disorders; Sexual Dysfunction, Physiological; Sodium-Potassium-Exchanging ATPase; Tics; Tryptophan; Tyrosine

The isoprenoid pathway produces three key metabolites: i) digoxin (a membrane sodium-potassium ATPase inhibitor which can regulate intracellular calcium/magnesium ratios), ii) dolichol (which regulates N-glycosylation of proteins), and iii) ubiquinone (a free radical scavenger), all of which are important in bone and joint metabolism. The pathway was assessed in senile osteoporosis, spondylosis, and osteoarthritis. Digoxin could possibly play a role in the genesis of cerebral dominance because it can regulate multiple neurotransmitter systems. The pathway was also assessed in individuals of differing hemispheric dominance for comparison and to find out the role of cerebral dominance in the pathogenesis of these diseases. The plasma/serum-activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, and tryptophan/tyrosine catabolic patterns, as well as RBC Na(+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism, free radical metabolism, and membrane composition were also studied. The pathway was upregulated with increased digoxin synthesis in patients with spondylosis and osteoarthritis. In this group of patients, the glycoconjugate levels and dolichol levels were increased and lysosomal stability reduced. The ubiquinone levels were low and free radicals increased in spondylosis and osteoarthritis. On the other hand, in senile osteoporosis, the isoprenoid pathway was downregulated and digoxin synthesis reduced. The glycoconjugate and dolichol levels were low and lysosomal stability increased. The ubiquinone levels were increased and free radical production increased in senile osteoporosis. The significance of these changes in the pathogenesis of osteoarthritis, spondylosis, and osteoporosis is discussed. The hyperdigoxinemic state is seen in osteoarthritis and spondylosis and in right hemispheric dominance. The hypodigoxinemic state is seen in left hemispheric dominance and senile osteoporosis. Hemispheric dominance plays a crucial role in deciding the predisposition to bone and joint diseases. Right hemispheric chemical dominance predisposes to spondylosis and osteoarthritis. Left hemispheric chemical dominance predisposes to osteoporosis.

Topics: Digoxin; Dolichols; Dominance, Cerebral; Erythrocytes; Female; Free Radicals; Glycoconjugates; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Lysosomes; Magnesium; Male; Matched-Pair Analysis; Osteoarthritis; Osteoporosis; Sodium-Potassium-Exchanging ATPase; Spinal Osteophytosis; Ubiquinone