lipid metabolism chapter 29, stryer short course
DESCRIPTION
TAG Synthesis Mainly in Liver Packaged in chylomicronsTRANSCRIPT
![Page 1: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/1.jpg)
Lipid Metabolism
Chapter 29, Stryer Short Course
![Page 2: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/2.jpg)
Lipid anabolism
• Triacylglyderides• Membrane components• Cholesterol– Regulation
• Steroids
![Page 3: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/3.jpg)
TAG Synthesis
• Mainly in Liver• Packaged in
chylomicrons
![Page 4: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/4.jpg)
![Page 5: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/5.jpg)
Cholesterol Biosynthesis
• Three Stages: Acetyl CoAIsopentyl diphosphateSqualeneCholesterol
![Page 6: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/6.jpg)
Stage 1• Similar to ketogenesis, but in
cytosol• HMG-CoA reductase is main
regulatory enzyme• Mevalonate made into isoprene
building block for many lipids
![Page 7: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/7.jpg)
![Page 8: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/8.jpg)
Stage 2
• Head-to-tail to form farnesyl group
• Tail-to-tail to form squalene
![Page 9: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/9.jpg)
Stage 3
• Carbocation cascade sets the A-D rings and stereocenters
• Further processing
![Page 10: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/10.jpg)
Regulation of Cholesterol Synthesis• HMG-CoA Reductase• Local covalent regulation
– AMP-protein kinase down regulates synthesis (like fatty acid)
• Transcription – Low [cholesterol] releases
SER (sterol regulatory element) to nucleus to upregulate the Reductase
• Translation inhibition• Degradation of enzyme
![Page 11: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/11.jpg)
Lipoprotein Metabolism
• Liver is the packaging center
• VLDL are sent out of liver
• Constant cycling of LDL in blood
• HDLs are “good cholesterol”
LDL =
![Page 12: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/12.jpg)
LDL receptors
![Page 13: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/13.jpg)
Atherosclerosis• Formation of plaques from
high LDL• LDLs oxidize and cause
inflammation• “hardening of the arteries”• Familial hypercholesterolemia
from absence of LDL receptors on cells
• HDL picks up cholesterol scavenged by macrophages
• Low HDL leads to macrophages contributing to plaque/artery damage
![Page 14: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/14.jpg)
Medical Approach to High Cholesterol
• Deprive cells of cholesterol– Dietary– De novo
• Cell responds by upregulating LDL receptors to pull LDLs out of blood
![Page 15: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/15.jpg)
Reduce dietary cholesterol
• Inhibit reabsorption of bile salts in intestine so that cholesterol is used up making bile salts
• Drug: positively charged polymers that are not absorbed
![Page 16: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/16.jpg)
Block de novo synthesis
• Statins inhibit HMG-CoA Reductase• Problem: inhibits all steroid biosynthesis
![Page 17: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/17.jpg)
Medical Applications
• Parasites like malaria make isopentenyl diphosphate through a different mechanism
• A competitive inhibitor can selectively kill malaria
-OP
O
O O-
OH
OH
O
intermediate in cholesterol biosynthesis
-OP N
O O- OH
O
competitive inhibitor
![Page 18: Lipid Metabolism Chapter 29, Stryer Short Course](https://reader034.vdocuments.net/reader034/viewer/2022051521/5a4d1ad67f8b9ab05997307a/html5/thumbnails/18.jpg)
Biosynthetic Precursor
• Steroids– Sex hormones– Metabolic regulation– Kidney water/salt
balance• Vitamin D