Wednesday, 6 November 2013

Biochemistry

 Lecithin: cholesterol acyltransferase (LCAT) activity is associated with HDL containing apo A-I. As cholesterol in HDL becomes esterified, it creates a concentration gradient and draws in cholesterol from tissues and from other lipoproteins..

Coprostanol is the principal sterol in the feces; it is formed from cholesterol by the bacteria in the lower intestine.

The principal rate-limiting step in the biosynthesis of bile acids is at the cholesterol 7alpha-hydroxylase reaction.The activity of the enzyme is feedback-regulated via the nuclear bile acid-binding receptor farnesoid X receptor FXR

 LDL:HDL cholesterol ratio a good predictive parameter

Ezetimibe reduces blood cholesterol levels by inhibiting the absorption of cholesterol by the intestine by blocking uptake via the Neimann-Pick C-like 1 protein.
Other drugs used include fibrates such as
clofibrate and
gemfibrozil and
nicotinic acid,
which act mainly to lower plasma triacylglycerols by decreasing the secretion of triacylglycerol and cholesterol-containing VLDL by the liver...

Hyperlipoproteinemias
   Familial lipoprotein lipase deficiency (type I)
  Hypertriacylglycerolemia due to deficiency of LPL, abnormal LPL, or apo C-II deficiency causing inactive LPL.  Slow clearance of chylomicrons and VLDL. Low levels of LDL and HDL. No increased risk of coronary disease.  

   Familial hypercholesterolemia (type IIa)  Defective LDL receptors or mutation in ligand region of apo B-100.  Elevated LDL levels and hypercholesterolemia, resulting in atherosclerosis and coronary disease.  

    Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia  Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor.1
   Increase in chylomicron and VLDL remnants of density < 1.019 (VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis.  

    Familial hypertriacylglycerolemia (type IV)  Overproduction of VLDL often associated with glucose intolerance and hyperinsulinemia.  Cholesterol levels rise with the VLDL concentration. LDL and HDL tend to be subnormal. This type of pattern is commonly associated with coronary heart disease, type II diabetes mellitus, obesity, alcoholism, and administration of progestational hormones.
  
    Familial hyperalphalipoproteinemia Increased concentrations of HDL.A rare condition apparently beneficial to health and longevity.  

    Hepatic lipase deficiency .. 
Deficiency of the enzyme leads to accumulation of large triacylglycerolrich HDL and VLDL remnants.  Patients have xanthomas and coronary heart disease.  

    Familial lecithin:cholesterol acyltransferase (LCAT) deficiency  Absence of LCAT leads to block in reverse cholesterol transport. HDL remains as nascent disks incapable of taking up and esterifying cholesterol.  Plasma concentrations of cholesteryl esters and lysolecithin are low. Present is an abnormal LDL fraction, lipoprotein X, found also in patients with cholestasis. VLDL is abnormal (-VLDL). 
 
 Familial lipoprotein(a) excess  Lp(a) consists of 1 mol of LDL attached to 1 mol of apo(a). Apo(a) shows structural homologies to plasminogen.  Premature coronary heart disease due to atherosclerosis, plus thrombosis

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