Correlation Between Cholesterol Levels and Coronary Heart Disease Events 18 RULE 16 For every 1%increase 141 in LDL-C, there is a 1% 12 increase in CHD events Age-adjusted 6-year 10 CHd death rate per 1000 men 8 ●●● 0 140160180200220240260280300 n=325.000men Serum total cholesterol(mg/dL) Martin MJ et al. Lancet. 1986: 11: 933-936
0 2 4 6 8 10 12 14 16 18 140 160 180 200 220 240 260 280 300 Serum total cholesterol (mg/dL) Age-adjusted 6-year CHD death rate per 1000 men Correlation Between Cholesterol Levels and Coronary Heart Disease Events Martin MJ et al. Lancet. 1986;II:933-936. n=325,000 men RULE: For every 1% increase in LDL-C, there is a 1% increase in CHD events
LDL ow density lipoprotein) LDL is associated with increased heart disease lousy cholesterol”“ bad cholesterol The major carrier of cholesterol in the blood Role: transport cholesterol to peripheral tissues Half-life: 24 hrs(every day about half of the circulating LDL is removed via receptor mediated endocytosis) Lp(a lipoprotein (a)l Lp(a is extracted from LDL Lp(a)is a independent risk factor of atherosclerosis
• LDL is associated with increased heart disease “lousy cholesterol” “bad cholesterol” • The major carrier of cholesterol in the blood LDL (low density lipoprotein) • Role: transport cholesterol to peripheral tissues • Half-life: ~ 24 hrs (every day about half of the circulating LDL is removed via receptor mediated endocytosis) Lp(a) [lipoprotein (a)] • Lp(a) is extracted from LDL • Lp(a) is a independent risk factor of atherosclerosis
Low-Density Lipoprotein (LDL) Unesterified Apo B-100O cholesterol Phospholipid Cholesterol ester Triglyceride Diameter 225-275A
Low-Density Lipoprotein (LDL) Apo B-100 Diameter 225-275 Å Phospholipid Unesterified cholesterol Cholesterol ester Triglyceride
DIETARY FAT LNVER To endocrine AND CHOLESTERO glands for steroid hormone synthesis Bile salt Biosynthesis Pickup of cholesterol Fecal of fats and cholesterol cholestero Intestine LDL ◎○ LDL receptor Lymph o88 protein Remnant FERIFHERAL Chylomicrons chylomicrons VLDL (Remnants) TISSUES and cholesteric muscles TG ald TC various organs) Capillaries Capillaries Apo B-100 Hydrolysis of chole sterol triacylglycerols TG in capillaries Plasma LCAT ○ Hydrophilic layer Lipoprotein lipase (protein, phospholipids O Triacylglycerols Glycerol Fatty acids B-Oxidation in peripheral tissues Cholesterol Transpon by serum albumin Returned to liver Resynthesis and storag for glucose synthesis mainly in adipose tissue
LPL TG and TC TG TC
Cholesterol Synthesis Pathway Acetyl-CoA Acetoacetyl-CoA S-COA S-COA HMG-CoA(羟甲基戊二酸甲酰辅酶A S-COA HMG-COA Reductase OH Mevalonate(甲羟戊酸,MVA Dolichol 人人人 oPP Farnesyl-PP Haem Ubiquinone Farnesylated Proteins (人人人), Squalene Lipoprotein Cholesterol Vitamin D Bile Acids Steroid Hormones Istvan E and Deisenhofer J Science 2001: 292: 1160-1164
Cholesterol Synthesis Pathway （羟甲基戊二酸甲酰辅酶A） （甲羟戊酸，MVA）