Week 7: Lipid Overview Flashcards
What are some of the characteristics of lipid?
- Heterogenous group of hydrophobic molecules
- Insoluable in aqueous solution
- Compartmentalize in membranes or stored as TAGs in adipose
- Major energy source in body
- Precursors for vitamins and signaling molecules
What proteins transport lipids in the blood?
Albumin and lipoprotein
What are the 4 main function of fatty acids?
- Fuel molecules are stroed by TAGs
- Components of phospholipids and glycolipids
- Attached to proteins to localize the proteins to membranes
- Function as hormones and intracellular messengers
What type of molecules are important building blocks of membranes?
Amphipathic
What covalently attaches proteins to the membrane?
GPI anchors
What are examples of fatty acid hormones and intracellular messengers?
- PIP2
- IP3
- DAG
- GPCR Gqa signalling
In what ways are fatty acids used as fuels?
- Long chain FA are oxidized as fuels
2. FAs are released from adipose tissue between meals, during overnight fasting, or periods of increased fuel demand
What occurs when FA is released from adipose between meals?
- Decresaed insulin level and increased glucagon levels
- Activates lipolysis
- Free FA’s are transported to the tissues
What fatty acid molecule is the majority in biological systems?
Triacylglycerols (TAGs)
What are TAGs function in the body?
- Primary storage of body fat
2. Serve as concentrated stores of metabolic energy
What components form TAGs?
- Esterification of 3 fatty acids to glycerol
- Ester groups form the polar head
- Tails are nonpolar
Why are TAGs less soluable in water than fatty acids?
Esterification of the carboxylate group
How and when are ester linkages hydrolyzed?
Lipases when fatty acids are being used by organism
What are the advantages of using fats over polysaccarides?
- Fatty acids carry more energy per carbon because they are more reduced
- Fatty acids carry less water per gram because they are nonpolar
What’s the difference between glucose/glycogen and fats in regards to energy supply?
- Glucose are for short-term energy needs and quick delivery time
- Fats are for long-term energy needs, good stroage, and slow delivery
How are TAGs stored?
- Anhydrous form
- Stored in large droplets in the cytoplasm of adipocytes (adipose tissue)
- Muscle cells also store TAGs
Why are TAGs considered energy rich?
More reduced then glycogen
Compare the amount of energy fats and glycogen provide
1 g of TAG stores 4x more energy than 1 g of glycogen
What are the methods of digesting dietary lipids?
- Digestion begins in the stomach
- Lipase in secreted from glands in the back of tongue and in stomach
- Lipase breaks down TAG molecules that contain short and medium chain (<12 Cs) fatty acids
What are the steps of TAG metabolism?
- Emulsification of TAGs by bile salts
- Hydrolysis of TAGs by intenstinal lipases to generate free fatty acids
- Resynthesis of TAG inside intestinal epithelial cells
- Packaging of TAGs into large lipoprotein particles
- Export of chylomicrons to the lymphatic system
- Entry of chlomicrons into circulatory system through the left subclavian vien
What occurs during the emulsification of TAGS?
- Bile salts are produced in the liver and stored and secreted by the gallbladder
- Lipids are emulsified by bile salts and peristalsis
What occurs during the hydrolysis of TAG in the instestine?
- Cleaving TAGs into glycerol and fatty acids
2. Generation of free fatty acids because TAGs were too large to be taken up by mucosal cells of intestinal villi
What are the large lipoprotein particls that package TAGs?
Chylomicrons
What are chylomicrons’ contents?
- TAG
- Proteins
- Phospholipids
- Cholestrol
What is the process of chylomicrons being transported into the body?
- Carries lymph, water, chylomicrons from the lymphatic system to the blood
- Carried by the blood to the hepatic portal vein to the liver
- Transported to adipose tissue for storage
- Transported to muscle cells to use for energy
How is digestion of dietary lipids instigated by pancreatic lipases?
- Dietary TAGs form lipid droplets in the stomach
- Because TAGs are insoluable, it is incorporated into micelles from bile salt ready to be digested
- Pancreatic lipases convert TAGs into 2 fatty acids and monacylglycerol
- Products are carried by miscelles to intestinal epithelium cells for absorption
What is Alli (Orlistat)?
- Anti-obesity drug
- Inhibits gastric and pancreatic lipases
- Decreases fat absorption resulting in weight loss
What are the side effects of using Alli (Orlistat)?
- Oily spotting
- Flatus w/ discharge
- Fecal urgency
- Loose/fatty stool
- Fecal incontinence
What are the 3 stages of fuel processing?
- Degradation of TAG to release fatty acids and glycerol into the blood for transport to energy-requiring tissues
- Activation of the FA and transport into the mitochondria for oxidation
- Degradation of the FA to acetyl-coA by the CAC
How are TAGs hydrolyzed by hormone-stimulated lipases?
- Epinephrine and glucagon acting through GPCRs
- PKA hormone sensitive lipase intitiates breakdown of TAG into 3 FFA
- FFA are dilivered to tissues by albumin
- Glycerol is absorbed by liver for glycolysis or gluconeogensis
What occurs during the formation of fatty acid-coA?
- FA are attached to Coenzyme A by the catalyization of acyl-coa synthetase in cytosol
- Formation of PPi by pyrophosphatase makes this reaction irreversible
How is FA activated to enter the mitochandria?
2ATP is used to convert AMP to ATP
What happens to fatty-acyl coa when cell energy is low?
- Fatty-acyl-coA is imported to mitochandrial matirx by carnitine transport cycle
- Degrades FA by beta-oxidation into Acetly-coa, FADH2, and NADH
What happens to fatty-acyl coa when cell energy is high?
- Fatty acid synthesis is favored forward
2. Mitochandrial import of fatty acyl-coa is inhibited by malonyl-coa (presursor for FA synthesis)
What occurs during the carnitine transport cycle?
- FA are activated prior to entering the mitochondrial matrix
- Acyl-CoA is transfered to carnitine to be transported into mitochandria by translocase, carnitine shuttle
What is the rate limiting step for FA degradtion?
The trasfer of Acyl-CoA is transfered to carnitane by carnitine shuttle
How is the carnitine shuttle inhibited?
Malonyl-CoA
Where does FA synthesis primarily occur?
Cytoplasm of liver and lactating mammary glands cells from acetyl-coa, NADPH, and ATP
How does glucose contribute to lipid synthesis?
- Glucose is converted to acetyl-coa
2. Glucose is used to produce NADPH from the PPP
Describe the process of FA synthesis
- Glucose → pyruvate by glycolysis
- Pyruvate → Acetyl-CoA by pyruvate dehydrogenase in the matrix
- Acetyl-CoA movement from mitochandria to cytosol by the citrate shuttle
- Acetyl-CoA → citrate by citrate synthase
- Citrate is cleaved into OAA and Acetyl-CoA by ATP-citrase lyase
How is malonyl-coa formed?
Acetyl-CoA combines with HCOc- and is catalyzed by ACC to form malonyl-CoA
Requires ATP and irreversible
What are the components of a fatty acid?
- Activated acyl group
2. Activated malonyl group
What is the rate limiting step for fatty acid synthesis?
The conversion of Acetyl-CoA to Malonyl-CoA
How is FA synthesis regulated?
- ACC catalyzes the rate limiting step to where it is inhibited by palmitoyl-coa
- Activated by citrate
- Glucagon and epinephrine inactivates ACC stimulating lipolysis
- Insulin activates ACC to stimulate FA synthesis
- Malonyl-CoA inhibits FA import into mitochondria preventing B-oxidation
How is TAG synthesis regulated by insulin?
Stimulates FA and TAG synthesis
How are TAGs produced from FA?
FAs are added to glycerol by aceyltransferase
What happens when there is a lack of insulin?
- Increased lipolysis
- Increased FA oxidation
- Acetyl-CoA moves toward ketone bodies of CAC intermediates
- Failure to syntheisize fatty acids
What are the 4 steps of fatty acid degradation?
- Oxidation
- Hydration
- Oxidation
- Thiolysis
What occurs general during fatty acid degration?
Oxidation occurs at the beta-carbon atom
How do unsaturated FAs go achieve b-oxidation?
- B-oxidation occurs till double bond
- Isomerase changes the cis double bond of unsatruated fat to trans
- NADPH dependent reductase enzyme is required for polysaturated FA’s
- B-oxidation continues
How is b-oxidation of odd carbon FAs achieved?
- Generation of propionyl-coa
2. Propionyl-coa is converted to succinyl-coa for the CAC
What is the difference between FA degradation and synthesis?
- Both consist of 4 steps that mirror each other
- FA degradation is an oxidative process yielding Acetyl-CoA
- FA synthesis is a reductive process that begins with Acetyl-CoA
What occurs during the catabolism of FAs?
- Produces Acetyl-CoA
- Produces reducing power (NADH, FADH2)
- In the mitochondrial matrix
What occurs during the anabolism of FAs?
- Requires acetyl-CoA and malonyl-CoA
- Requires reducing power from NADPH
- Takes place in cytosol
