Chapter 29: Lipid Synthesis: Storage Lipids, Phospholipids, and Cholesterol Flashcards
What is the storage form of FAs?
Triacylglycerol
Lipids are made from _____ or from their breakdown products.
Fatty acids
Phospholipids and sphingolipids make up…
Membrane lipids
Membrane components and precursor to steroid hormones
Cholesterol
What is the precursor of storage lipids?
Phosphatidate
Phosphatidate (diacylglycerol 3-phosphate) is formed by the addition of _____ to _____.
Two fatty acids to glycerol 3-phosphate
Glycerol 3-phosphate –> _____ –> _____.
–> Lysophosphatidate –> Phosphatidate
What is bound to ER and synthesizes triacylglycerol from phosphatidate and acyl CoA in liver?
Triacylglycerol synthase
TAG is transported to _____ or _____
Muscle (fuel) or Adipose tissue (storage)
Phosphatidate –> DAG –>
TAG
Phosphatidate is the precursor to make…
Triacylglycerols (TAG)
Phospholipids are generated from _____ and _____ in the ER.
Phosphatidate and Alcohol
Phospholipid synthesis requires the activation of _____ to provide the needed energy
Either alcohol or phosphatidate
DAG is activated by forming _____.
CDP-diacylglycerol
In other cases, the alcohol is activated by _____ and subsequent _____ to form _____.
Activated by phosphorylation and subsequent reaction with CTP to form CDP-alcohol
The activated alcohol in phospholipid synthesis reacts with _____ to form the phospholipid.
Diacylglycerol
Sphingolipids are synthesized from _____.
Ceramide
Sphingolipids: Membrane lipids found in all eukaryotic cells, have a _____ instead of a glycerol bakcbone.
Sphingosine backbone
Sphingolipids are synthesized from _____ and _____.
Palmitoyl CoA and serine
What is the initial product of sphingolipid sythesis?
Ceramide
The _____ of ceramide is substituted to form other sphingolipids.
Terminal hydroxyl group
_____ is found in the extracellular fluid in lungs and prevent lung collapse after exhaling.
Dipalmitoyl phosphatidylcholine
Describe Respiratory Disease Syndrome
Failure to synthesize sufficient dipalmitoyl phosphatidylcholine, leading to collapse of the lung
Describe Tay-Sachs Disease.
- Inability to degrade ganglioside (phospholipids) due to lack of beta-N-acetylhexosaminidase in lysosomes
- Neurons become swollen with lipid-filled lysosomes, which leads to lack of psychomotor skills and blindness
- Tay-Sachs disease results in death by age 3
What is a key regulatory enzyme in lipid metabolism?
Phosphatidic Acid Phosphatase
What catalyzes the conversion of phosphatidate to diacylglycerol?
Phosphatidic acid phosphatase (regulates lipid metabolism)
Different lipids are synthesized depending on whether the phosphatase is _____ or _____.
Active or Inactive
Loss of phosphatase activity in mice results in loss of _____ and the development of _____.
Loss of body fat Development of insulin resistance
Excess phosphatase activity results in _____.
Obesity
No cholesterol = ?
No membrane function
Cholesterol is synthesized from _____.
Acetyl Coenzyme A
_____ is the primary site of cholesterol synthesis.
Liver
All 27 carbons of cholesterol are derived from _____.
Acetyl CoA
Cholesterol is synthesized from acetyl CoA to _____ to _____.
Mevalonate to isopentenyl pyrophosphate
6 molecules of isopentenyl pyrophosphate are condensed into _____.
Squalene
Squalene is cyclized into…
Cholesterol
What is the rate-limiting step of cholesterol synthesis?
Mevalonate formation
_____ initiates the synthesis of cholesterol
Formation of mevalonate
First step in the synthesis of cholesterol is the formation of mevalonate by…
HMG-CoA Reductase
HMG-CoA Reductase catalyzes the _____ and is the major _____ for cholesterol synthesis.
Catalyzes the committed step and is the major control site
HMG-CoA Reductase is an _____ in the _____.
Integral membrane protein in the ER
In other words, mevalonate determines…
How much cholesterol is synthesized by the cell
HMG-CoA reductase is controlled by four different mechanisms in response to cellular cholesterol levels:
- Regulation of transcription
- Covalent modification
- Regulation of translation
- Control of degradation
HMG-CoA Reductase synthesis rate is controlled by…
SREBP
HMG-CoA Reductase: When cholesterol levels increase,
Degradation of the reductase occurs
HMG-CoA Reductase: Phosphorylation will
Inactivate the enzyme
Cholesterol and triacylglycerols are NOT _____ and transported in the blood in form of _____ particles.
NOT water-soluble and transported in the form of lipoprotein particles
Lipoprotein particles consist of a _____ component and various _____.
Protein component and various lipids
The protein(s) serve to _____ the lipids and to _____ the particles to specific targets.
Serve to solubilize the lipids and to direct the particles to specific targets (specific tissues)
Lipoprotein particles are classified according to _____.
Increasing density
Proteins are _____ than lipids.
Denser
The higher density lipoproteins have MORE protein
VLDL is what % lipid?
98%
Cholesterol is carried by _____.
LDLs.
High levels of HDL…
Decrease the risk for heart disease
LDL _____ bloodstream; HDL _____ bloodstream.
LDL brings chol. to bloodstream; HDL removes chol. from bloodstream
The major carrier of cholesterol in the blood
Low-density lipoprotein (LDL)
Carries cholesterol released into the blood back to the liver - reverse cholesterol transport
High-density lipoprotein (HDL)
Which type is known as the ‘bad’ cholesterol?
LDL - can cause heart attacks
LDL plays a central role in…
Cholesterol Metabolism
LDLs deliver cholesterol to peripheral tissues and cholesterol enters the cell by _____.
Receptor-mediated endocytosis
What is the genetic disease that results from the absence of functional LDL receptor?
Familial hypercholesterolemia
- High levels of cholesterol and LDL in plasma
- Excess LDL contribute to development of heart attacks
What is the goal to treat high blood cholesterol?
- Goal is to increase # of LDL-R to more effectively remove cholesterol
How do you treat high blood cholesterol? 2 Treatments
- Decrease new cholesterol synthesis by inhibition of HMG-CoA reductase by a class of drugs called statins.
- Block the uptake of dietary cholesterol
- Blocked by ingesting a resin that binds to the bile salts
HDL protects against…
Atherosclerosis
HDL is considered the ‘good’ cholesterol because it can _____ by retrieving cholesterol from other tissues to the liver for excretion.
Prevent heart attacks
What is the precursor to steroid hormones, vitamin D and bile salts?
Cholesterol
Steroid hormones are crucial _____.
Signaling molecules
All five major classes of steroid hormones are derived from _____.
Cholesterol
Vitamin D is derived from cholesterol by _____.
Energy of sunlight
Regulation of calcium and phosphate metabolism
Vitamin D
Active form of vitamin D formed from cholesterol
Calcitriol
Deficiency of vitamin D results in…
- Rickets: inadequate calcification of cartilage and bone
In adults, vitamin D deficiency results in…
Osteomalacia, a condition characterized by soft and weak bones
T or F: HMG CoA reductase catalyzes the first committed step of cholesterol synthesis.
True
T or F: HMG CoA reductase can be regulated by phosphorylation.
True
T or F: The absence of sterols results in an increase in HMG CoA reductase degradation
False
T or F: SREBP is involved in transcriptional regulation of the HMG CoA reductase gene
True
T or F: Statins are competitive inhibitors of HMG CoA reductase.
True
Lipids in the intestine are coated with _____ and digested by _____?
- Coated with bile salts
- Digested by pancreatic lipases
Which is NOT a method for regulation of HMG CoA reductase?
- Inactivation due to phosphorylation by AMP-dependent kinase
- Alteration in rate of translation of reductase mRNA by dietary cholesterol
- Regulation of rate of synthesis of reductase mRNA by SREBP
- Proteolytic degradation of reductase controlled by cholesterol levels
- Transportation of reductase to the mitochondria controlled by cholesterol levels
Transportation of reductase to the mitochondria controlled by cholesterol levels
Cholesterol is used in formation of:
- Bile salts
- Testosterone and other steroid hormones
- Cholesterol esters
- Vitamin D
All are correct
If levels of cholesterol are low:
- Proteolysis of HMG CoA reductase is increased
- HMG CoA reductase is phosphorylated by AMP-activated protein kinase
- HMG CoA reductase is translocated to the nucleus
- SREBP is cleaved by a protease, allowing the DNA binding domain to increase transcription of the HMG CoA reductase gene
- HMG CoA reductase expression is not altered in any way
SREBP is cleaved by a protease, allowing the DNA binding domain to increase transcription of the HMG CoA reductase gene
Lipoproteins:
- Are used primarily to transport amino acids throughout the body
- Contain hydrophobic cores with triacylglycerols and cholesterol esters
- Have hydrophobic surfaces with charged carbohydrates
- Contain only cholesterol as a lipid component
- Function only in the liver
Contain hydrophobic cores with triacylglycerols and cholesterol esters