《生物化学》课程PPT教学课件（留学生）Chapter 20 The metabolism of cholesterol

BIOCHEMISTRYANDMOLECULARBIOLOGYchapter 20The metabolism ofcholesterolDepartment of Biochemistryand Molecular Biology,MedicineSchool

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY chapter 20 The metabolism of cholesterol

ABIOCHEMISTRYANDMOLECULARBIOLOGYOutlineKmetabolism of cholesterolOverviewStructureof cholesterolSynthesis of cholesterolDegradationofcholesterol*Metabolismof bileacidsFunction of bile acidsDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Outline * metabolism of cholesterol ✓ Overview ✓ Structure of cholesterol ✓ Synthesis of cholesterol ✓ Degradation of cholesterol *Metabolism of bile acids ✓ Function of bile acids

BIOCHEMISTRYANDMOLECULARBIOLOGY1.metabolism of cholesterolThesynthesis ofcholesterolThe degradation of cholesterolDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY The synthesis of cholesterol The degradation of cholesterol 1. metabolism of cholesterol

BIOCHEMISTRYANDMOLECULARBIOLOGY1)overviewandinplasmaCholesterol is presentintissueslipoproteins either as free cholesterol or, combined with along-chain fatty acid, as cholesteryl esterDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Cholesterol is present in tissues and in plasma lipoproteins either as free cholesterol or, combined with a long-chain fatty acid, as cholesteryl ester. 1) overview

BIOCHEMISTRYANDMOLECULARBIOLOGY2)Structureofcholesterol2221202623181217242511162713191415928107HO3546Department of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY HO 1 2 3 4 5 6 7 8 9 10 11 19 12 13 14 15 16 17 18 20 21 22 23 24 25 26 27 2) Structure of cholesterol

BIOCHEMISTRYANDMOLECULARBIOLOGY3)SynthesisofcholesterolSynthesis site:all kinds of cells except mature brain and erythrocytes(cytosol and endoplasmic reticulum)the material of synthesis :acetyl CoA、ATP、NADPH + H+Department of Biochemistryand Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY the material of synthesis： acetyl CoA、ATP、NADPH + H+ Synthesis site： all kinds of cells except mature brain and erythrocytes （cytosol and endoplasmic reticulum） 3) Synthesis of cholesterol

北BIOCHEMISTRYANDMOLECULARBIOLOGYCholesterol is synthesized by virtually all tissues inhumans, although liver, intestine, adrenal cortex, andreproductive tissues including ovaries, testes, andplacenta make the largest contributions to the body'scholesterol poolDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY Cholesterol is synthesized by virtually all tissues in humans, although liver, intestine, adrenal cortex, and reproductive tissues including ovaries, testes, and placenta make the largest contributions to the body’s cholesterol pool

BIOCHEMISTRYANDMOLECULARBIOLOGYAll the carbon atoms in cholesterol are provided byacetate, and NADPH provides the reducing equivalentsThe pathway is driven by the hydrolysis of the high-energy thioester bond of acetyl CoA and the terminalphosphate bond of ATP. Synthesis occurs in thecytoplasm, with enzymes in both the cytosol and theendoplasmic reticulumDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY All the carbon atoms in cholesterol are provided by acetate, and NADPH provides the reducing equivalents. The pathway is driven by the hydrolysis of the high￾energy thioester bond of acetyl CoA and the terminal phosphate bond of ATP. Synthesis occurs in the cytoplasm, with enzymes in both the cytosol and the endoplasmic reticulum

BIOCHEMISTRYANDMOLECULARBIOLOGYpathway:1.Mevalonic acid synthesize2.The synthesis of squalene3.The synthesis of cholesterolDepartment of Biochemistry and Molecular Biology,Medicine School

Department of Biochemistry and Molecular Biology, Medicine School BIOCHEMISTRY AND MOLECULAR BIOLOGY pathway： 1.Mevalonic acid synthesize 2.The synthesis of squalene 3.The synthesis of cholesterol

Pathway:COOHthiolaseCH2HMGCoAsynthase2CH,COCoACH,COCH,COCoAC(OH)CH3HSCoACH3COCoACH2COOHCOCOACH2HMGCoA reductaseCOHCH3@-@-O-CH--CH-C-CHCH2CHCH2OHDimethylallyl(mevalonicacid,MVA)pyrophosphatecholesterol lanosterol squalene

Pathway: 2CH3COCoA CH3COCH2COCoA COOH CH2 C(OH)CH3 CH2 COOH COCoA CH2 C(OH)CH3 CH2 CH2OH squalene HSCoA CH3COCoA thiolase HMGCoA synthase HMGCoA reductase （mevalonic acid,MVA) Dimethylallyl pyrophosphate P P - -O-CH2-CH=C-CH3 CH3 lanosterol cholesterol