Cv Path Cholesterol

Front 1

Describe triglyceride

Back 1

-90% of Dietary fat intake
-95% of fat stored in tissue

Front 2

Describe phospholipids

Back 2

Essential component of cell membranes

Front 3

Describe Cholesterol and Cholesterol Esters

Back 3

-Very hydrophobic
-Solid at body temperature
-Integral part of membranes

Front 4

Describe sources of cholesterol

Back 4

-Cholesterol can be obtained through diet or de novo synthesis
-Uptake is carried from the intestines to adipose tissue and the liver by chylomicrons
-De novo synthesis is from Acetyl CoA in the liver

Front 5

What is cholesterol used for?

Back 5

-Several steroid hormones are derived from cholesterol (including glucocorticoids, androgens, mineralcorticoids, estrogents)
-A precursor for bile salts and vitamin D

Front 6

Describe how the body processes dietary lipid

Back 6

-Initially broken down by pancreatic lipase
-Absorbed by the intestinal mucosa
-Chylomicrons formed
-Chylomicrons travel through lymph and circulation
-Exposed to other lipases on the way to tissue and muscle

Front 7

Describe the interaction between chylomicrons and lipoprotein lipase.

Back 7

-Endothelium has lipoprotein lipase
-Enzymes break down the lipids in the chylomicron
-Cholesterol and free fatty acids are released
-Available for different tissues
-What remains goes to liver and through the process of converting chylomicrons to VLDL

Front 8

Describe Lipoproteins

Back 8

-Particles found in plasma
-Transport lipids including cholesterol
-Inner droplet primarily triglycerides and cholesterol esters
-A solubilizing surface of a single monolayer of phospholipids and unesterified cholesterol
-Specific proteins (apolipoproteins) are attached to the outer lipid layer through specific lipophilic domains

Front 9

What are the different classes of lipoprotein?

Back 9

-Chylomicrons
-Very Low Density Lipoproteins (VLDL)
-Intermediate Density Lipoproteins (IDL)
-Low Density Lipoproteins (LDL) (uptake controlled by LDL receptor)
-High Density Lipoproteins (HDL): Circulate continuously in plasma. They contain an enzyme that converts free cholesterol to cholesterol esters and aids in the transport of cholesterol

Front 10

How are Apoproteins classified?

Back 10

On the basis of density and electrophoretic mobility

Front 11

What are the importtant apoproteins?

Back 11

B48: Only in chylomicrons
B100 - Principle protein in LDL

These are large proteins that have a role in atherosclerosis

Front 12

What do apoproteins do?

Back 12

The apoproteins maintain the intergrity of the particles and helps them to be recognized by different cells. They can stimulate or integrate some enzymes in the process of metabolism of the proteins.

Front 13

Describe the composition and properties of HDL

Back 13

Diameter: 5-15nm
Core Lipids: Cholesterol Esters
Major Protein: ApoA-1
Mechanism of Lipid Delivery: Transfer of cholesterol esters to LDL and IDLh

Front 14

Describe the composition and properties of LDL

Back 14

Diameter: 18-28nm
Core Lipids: Cholesterol Esters
Major Protein: ApoB
Mechanism of Lipid Delivery: Cholesterol esters receptor-mediated endocytosis by liver and conversion to LDL

Front 15

Describe the composition and properties of chylomicrons

Back 15

Diameter: 100-500
Core Lipids: Triacylglycerol
Major Protein: ApoB
Mechanism of Lipid Delivery: Hydrolysis by Lipoprotein Lipase


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Front 16

Describe the difference in composition of chylomicrons, VLDL, LDL, and HDL

Back 16

Chylomicrons have the most triacylglycerol and the leads protein

HDL has the most protein and the least triacyglycerol

Front 17

Describe the breakdown of chylomicrons

Back 17

-ApoC2 activates lipoprotein lipase which catalyzes the hydrolysis of triacylglycerols
-The chylomicron remnant is taken up by the ApoB48/Remnant receptor in the liver

Front 18

Describe the mobilization of triacyglycerols

Back 18

-Hormones regulate the conversion of ATP to cAMP
-cAMP activates lipoprotein lipase
-Lipoprotein lipase interacts with the lipid droplet to cause the release of glycerol and fatty acids

Front 19

What do lipases do?

Back 19

Hydrolyze triacylglycerols, releasing one fatty acid at a time and forming diacylglycerols, monoacylglycerol, and glycerol

Front 20

What are the different lipases?

Back 20

Pancreatic Lipase - Hydrolyzes dietary TG

Lipoprotein Lipase - Acts on lipoprotein triglycerides

Hormone-sensitive lipase - Responsible for mobilization of adipose stores of TG. Regulated by insulin, adrenalin, and glucagon

Front 21

How is cholesterol removed from the body?

Back 21

Bile acids

Front 22

Describe hepatic cholesterol synthesis

Back 22

-Acetate is used to make HMG CoA
-This becomes mevalonic acid through HMG-CoA reductase (rate limiting step)
-Through about 20 other steps cholesterol is made

Front 23

Describe HMG-CoA reductase

Back 23

-Integral membrane protein in the ER
-Different from mitochondrial HMG-CoA Reductase, which plays a role in Ketosis
-Carries out an irreversible reaction
-Is an important regulatory enzyme in cholesterol synthesis

Front 24

Describe VLDL Biogenesis

Back 24

VLDL is going to be synthesized and excreted through the circulation. The TG assembling together and going through the rough and smooth ER and then pass through the golgi apparatus as a vesicle to be excreted. The VLDL has lots of triglycerides and cholesterol. They have Apo-B and Apo-C and other proteins as well.

Front 25

Describe VLDL Metabolism

Back 25

VLDL goes through the cascade of the reaction and the delivering of the triglycerides and fatty acids to different tissues. It is carried through them with the HDL it will gain more cholesterol and apoproteins. With the impact of lipase it will release free fatty acids and turn to LDL or go back to the liver to carry the triglycerides to the body to deliver free fatty acids to the organs that are in need.

Front 26

Describe VLDL remnant uptake and converstion to LDL

Back 26

VLDL rements/IDL, if it contains ApoE, can be taken up by the ApoE/remnant receptor and made into LDL

Front 27

Describe the LDL receptor

Back 27

-Recognizes both ApoB and ApoE
-Active mainly in the liver

Front 28

Describe LDL uptake by tissues

Back 28

75% is taken in by the liver
3/4 of this is receptor mediated
1/4 is nonreceptor mediated

25% is taken up by extrahepatic tissue
2/3 of this is receptor mediated
1/3 is nonreceptor mediated

Front 29

Describe the formation of the LDL receptor

Back 29

LDL receptor is synthesized through the code in DNA. It goes through ER and golgi and then through the microsomes to the cell membrane. The LDL is taken into the cell and the cholesterol is removed. If there is a deficiency you get hypercholesteremia.

Front 30

Describe Familial Lipoprotein Lipase Deficiency

Back 30

-Caused by deficient activity of lipoprotein lipase (LPL)
-Encoded by the gene LDL
-Inherited in an autosomal recessive manner
-Childhood-onset with marked hypertriglyceridemia
-Symptoms include recurrent acute pancreatitis, eruptive cutaneous xanthomata, hepatosplenomegaly, chylomicronemia
-Diagnosis by enzyme/DNA testing
-No risk of premature atherosclerosis
-Treatment: Dietary restriction

Front 31

Describe Familial Hypercholesterolemia

Back 31

-Genetic diseases
-From one of many mutant alleles for the LDL receptor gene
-LDL uptake into cells defective
-Cholesterol accumulation in blood
-Homozygotes: 680mg/dL (atherosclerosis in childhood)
-Heterozygotes: 300mg/dL (atherosclerosis in middle age)
-Healthy level 175mg/dL
-Treated with inhibitors of de novo cholesterol biosynthesis and cholestryamine

Front 32

Describe Tangiers disease and Familial HDL Deficiency

Back 32

-Rare diseases that result from defects in the gene encoding the ABC1 protein
-Cholesterol-depleted HDL cannot acquire cholesterol from any cell lacking ABC1
-Cholesterol-depleted HDL is rapidly removed from the circulation so plasma HDL levels are 1-5% of normal
-Patients accumulate Cholesterol in lymphoreticular system (hepatomegaly and spleenomegaly)

Front 33

Describe type 1 hyperlipidemia

Back 33

-Elevated blood concentrations of chylomicrons
-Caused by either of two seperate genetic defects
Deficiency in ApoC2
Deficiency in Lipoprotein Lipase
-Symptoms: Plasma triacylglycerol levels >1000mg/dL. Eruptive Xanthomas and Pancreatitis

Front 34

Describe Abetalipoproteinemia

Back 34

-Genetic disease characterized by lack of ApoB-100
-Patients cannot synthesize chylomicrons, VLDLs and LDLs
-Symptoms: Malabsorption of fat, accumulation of lipid droplets within cells of the small intestine, spiny shaped red cells, neurological disease (ie, ataxia and retardation)

Front 35

Describe Type 3 Hyperlipidemia

Back 35

-Caused by defects in the gene encoding ApoE
-Patients Show Reduced Uptake of Chylomicrons and VLDL remnants
-Symptoms include increased risk of atherosclerosis

Front 36

Describe the relationship between ApoE and Alzheimer's Disease

Back 36

-Individuals homozygous for ApoE4 have a 16fold increased risk of Alheimer's Disease
-Individuals homozygous for ApoE3 have a mean age of onset of 90y
-ApoE may have a second role in stabilizing neuronal cytoskeleton

Front 37

Describe the regulation of cholesterol production

Back 37

There are many factors in balance, including insulin and glucagon

Front 38

Describe pancreatic lipase inhibitors

Back 38

-Pancreatic lipase hydrolyzes dietary TG
-Xenical = pancreatic lipase inhibitor (prevents absorption of dietary TG)