Chapter 15 ( Lipid Synthesis And Storage ) Flashcards
What is the primary product of fatty acid synthesis ?
Palmitic acid
The 2 essential fatty acids ?
Linolenic FA
Linoleic FA
What FA does Arachidonic acid formed from ? Its precursor for what ?
Linoleic acid Precursor for : Prostaglandins Thromboxanes Leukotrienes
How Omega-3 FAs in diet decrease cardiovascular disease risk ?
By replacing some of the arachidonic acid in platelet membranes which may lower the production of thromboxane and tendency of the platelets to aggregate
In which configuration are the double bonds of FAs?
Cis-configuration
How does fatty acids activation occur ?
By attaching Coenzyme A to them by fatty acyl-CoA synthetase
Role of insulin in fatty acids biosynthesis ?
Promotes many steps in the conversion of glucose into acetyl-CoA in liver :
1- glucokinase
2- PFK2/PFK1
3- pyruvate dehydrogenase
Both of the major enzymes of fatty acid synthesis are affected also by insulin :
1- acetyl-CoA carboxylase
2- fatty acid synthase
2 sources for NADPH in FA synthesis ?
HMP shunt
Malic enzyme
Acetyl-CoA carboxylase requirements and activators ?
Requires : ATP Biotin CO2 Activators : Insulin Citrate
Sources for glycerol-3-phosphate for triglyceride synthesis ?
1-Reduction of DHAP from glycolysis by glycerol-3-p dehydrogenase which present in both liver and adipose tissue
2-phosphorylation of free glycerol by glycerol kinase which found in liver only
Functions of Glycerophospholipids ?
Membrane synthesis
Producing hydrophilic layer on lipoproteins
Serve as reservoir of second messengers in cell membranes such as : DAG , IP3 and arachidonic acid
Chylomicrons : functions , attached apoproteins ?
Transport dietary triglyceride and cholesterol from intestine to tissues
ApoB-148
ApoC-ll
ApoE
Apo proteins ? Their functions ?
Apo A : activator of LCAT
Apo B , Apo E : involved in receptor lipoprotein interactions
Apo C : activator of LPL
VLDL function and its apoproteins ?
Transport triglyceride from liver to tissues
ApoB-100
ApoC-ll
ApoE
IDL function and its apoprotein ?
Picks up cholesterol from HDL to become LDL , picked up by liver
ApoB-100
ApoE
LDL function and its apoprotein ?
Deliver cholesterol into cells
ApoB-100
HDL function and its apoprotein ?
Picks up cholesterol accumulating in blood vessels
Deliver cholesterol to liver and steroidogenic tissues via Scavenger receptor (SR-B1)
Shuttles apoC-ll and apoE in blood
ApoA-1
Abetalipoproteinemia defect and hallmark ?
Defect in apoB-48 leading to accumulation of fat in enterocytes and hepatocytes
Hallmark : decreased triglycerides
Effects : malabsorption of fat soluble vitamins and the 2 essential fatty acids
Symptoms :
Steatorrhea
Cerebellar ataxia
Pigmentary degeneration the retina
Acanthocytes ( decreased vit E )
Possible loss of night vision ( decreased vit A )
Liver pathways for acquiring cholesterol ?
1- de novo synthesis
2- endocytosis of LDL
3- transfer of cholesterol from HDL vis SR-B1 receptor
4- endocytosis of chylomicron remnants with residual dietary cholesterol
Increased cholesterol in hepatocytes repress the expression of genes for what ?
1- HMG-CoA reductase
1- LDL receptor
2- SR-B1 receptor
Difference between ACAT and LCAT ?
ACAT : intracellular enzyme which makes cholesterol esters for storage
LCAT : blood enzyme which makes cholesterol esters for trapping in lipoproteins
Factors contributing to blood vessel endothelium damage ?
1- normal turbulence of blood
2- elevated LDL ( especially oxidized LDL )
3- free radicals from cigarette smocking
4- homocystinemia
5- diabetes
6- hypertension
Type 1 hypertriglyceridemia ? Defect ? Lipid elevated ? Lipoprotein elevated ? Symptoms ?
Defect : deficiency of familial lipoprotein lipase or apoC-ll Lipid elevated : triglyceride Lipoprotein elevated : chylomicrons Symptoms : Red orange eruptive xanthomas Fatty liver Acute pancreatitis Abdominal pain after fatty meal
Type lla(familial) hypercholesterolemia ? Deficiency of what ? Lipid elevated ? Lipoprotein elevated ? Symptoms ?
Autosomal dominant Deficiency of LDL receptor Lipid elevated : cholesterol Lipoprotein elevated : LDL Symptoms : Risk of atherosclerosis and its complications Homozygous die < 20 years Xanthomas of Achilles tendon Corneal arcus Tuberous xanthomas on elbows Xanthelasmas
Factors contributes to hyperlipidemia in Type 1 hypertriglyceridemia ?
Decreased glucose and triglyceride uptake in adipose tissue
Over active hormone-sensitive lipase
Underactive lipoprotein lipase
What’s the most common type of hyperlipidemia ?
Type V : patients have elevated triglycerides in VLDL and chylomicrons in response to a meal containing carbohydrates and fat
Functions of cholesterol in human ?
1- membrane synthesis
2- steroid and vitamin D synthesis
3- bile acids synthesis
Rate limiting enzyme of cholesterol synthesis ? Its direct product ? Activator ? Inhibitor ?
HMG-CoA reductase on the SER Direct product : Mevalonate Activator : insulin Inhibitor : glucagon , statin drugs Cholesterol repress its gene expression and increase its degradation
Uses of Farnesyl pyrophosphate in the body ?
1- synthesis of Coenzyme Q for ETC
2- synthesis of dolichol pyrophosphate , required cofactor in N-glycosylation of proteins in ER
3- prenylation of proteins ( posttranslational modification ) that need to be held in the cell membrane by a lipid tail , Example : p21ras G protein
Cholestyramine mechanism ?
Increase elimination of bile salts which force the liver to increase their synthesis from cholesterol which in turn increase LDL receptor expression allowing hepatocytes to remove more LDL cholesterol from the blood
Most common side effect of statin ?
Muscle pain due to decreased Farnesyl PPi which lead to decreased CoQ synthesis which is important for ETC in mitochondria , myoglobinuria may be associated
Function of glycerol kinase in liver other than triglyceride synthesis ?
During fasting it allows the liver to trap glycerol released into the blood from lipolysis in adipose tissue for subsequent conversion to glucose ( gluconeogenesis )
