Lipid Metabolism and Disorders Flashcards
What are the 3 types of dietary lipids
Triglycerides- principally
Cholesterol
Phospholipids
what are the types of dietary fatty acids in triglycerides
saturated
monounsaturated
polyunsaturated
where does lipid digestion occur
Occurs in small intestine
What role does bile play in lipid digestion
Bile is an emulsifier, it turns large droplets into small lipid droplets –> easier digestion
What role do pancreatic lipase and colipase play in lipid digestion
Break down TAG into 2 fatty acids and monoglyceride
What is the target of drug Orlistat and what is its function
Targets are pancreatic lipase and colipase
Function: drug designed to inhibit lipid digestion
what are the steps of lipid digestion
Large lipid droplets converted by bile salts (emulsifiers) into small lipid droplets.
Small lipid droplets are converted by bile salts, pancreatic lipase and colipase into water soluble micelles of Fatty acids and monoglycerides
describe the steps of lipid absorption
TRiglycerides (TAG) re-formed in intestinal cell –> TAG packaged with cholesterol, lipoproteins and other lipids to form chylomicrons –> chylomicrons released into lymphatic system by exocytosis
describe the transport of lipids in chylomicron from plasma to adipose tissue
PLASMA: TAG are packaged into large molecules known as chylomicron. The enzyme, Lipoprotein lipase breaks down chylomicron into FA.
ADIPOSE: FA travel to adipose tissue where they are broken down to TAG (storage), structural FA (phoshphlipids) and Oxidation (ATP).
Describe the transport of lipids in chylomicron from plasma to liver
PLASMA: Large chylomicron molecules become small chylomicron molecules as lipids travel to adipose tissue.
LIVER: small chylomicrons travel to liver and are packaged into VLDL
describe endogenous lipid transport
Chylomicrons in liver packaged into VLDL > VLDL travels in capillaries > LPL breaks it down to free fatty acids which is stored in the adipose tissue > LPL attacks VLDL and expresses IDL protein > IDL protein interacts with the liver and is converted into LDL > LDL travels in the plasma > peripheral tissues take up the LDL
What 3 processes can u make from FFA
Ketone bodies
Phospholipid synthesis
B-Oxidation (making ATP)
What is B-oxidation
generation of energy (ATP) from fatty acids
what is the 1st step of B-oxidation
fatty acids added to acetyl CoA to form fatty acyl-CoA (makes it more soluble)
where does B-oxidation occur
occurs within the mitochondria
Fatty acids must cross the ____________
inner mitochondrial membrane
Describe the function of carnitine
- carrier molecule that transports fatty acids to inner mitochondrial membrane
- derived from lysine and methionine
- high percentage in muscle (muslce carries out a lot of B oxidation)
Describe fatty acid entry to mitochondria
FACoA converted to FAcarnitine by CPT I (Carnitine Palmitoyl transferase I)
FAcarnitine is then converted to FACoA by CPT II
FACoA enters B oxidation
How does FACoA become Acetyl CoA
FACoA degraded by oxidation at the B-carbon.
Reduces size of fatty acid chain by 2 carbons each time
–> Acetyl CoA
What does B-oxidation yield
FADH2
NADH
Acetyl CoA
________ are an excellent source of ATP
Fatty acids
what is triglyceride synthesis
esterification of 3 fatty acids and glycerol
Describe triglyceride synthesis
- LPL hydrolyses TAG in chylomicrons
- DGAT re-esterifies to TAG
- glycerol obtained form glycolysis
what is lipolysis and when does it occur
Triglyceride breakdown into 3 FA and glycerol
Fasting state
what is hormone sensitive lipase and what does it do
Found in adipose tissue
Stimulates lipolysis
Activated by camp-dependent phosphorylation in response to adrenaline in fasted state, inhibited by insulin
Describe fatty acid synthesis
Reverse of B oxidation
Fatty acids built 2 carbons at a time
What are the key regulatory enzymes of fatty acid synthesis
Acetyl CoA Carboxylase (1st)
Fatty Acid synthase (2nd)
what is the function of Acetyl CoA Carboxylase (1st step)
Converts Acetyl CoA –> Malonyl CoA
what component does Acetyl coA carboxylase require to carry out its function
Biotin
what is the 2nd step of fatty acid synthesis where fatty acid synthase is involved
Acetyl CoA coupled to Malonyl CoA
7 successive steps by multifunctional enzyme- fatty acod synthase
where does fatty acid synthesis occur
occurs in cytoplasm
what does fatty acid syntehsis require
requires NADPH (pentose phosphate pathway)
how are ketones formed
B-oxidation leads to substantial amount of acetyl co A production
Too much Acetyl CoA makes ketones
If oxaloacetate not present, then acetyl coA does not go through the TCA cycle and will be converted to _____
ketones
give examples of ketone bodies
Acetoacetate
B-hydroxybutyrate
Acetone
Acetacetate can be converted to _____ and _______
Acetone
B-hydroxybutyrate
Describe formation of phospholipids
Diglyceride is made (same steps as Triglyceride)
Then, combined with an alcohol
High levels of phospholipid synthesis occurs in what type of cells
Rapidly-dividing cells
can essential fatty acids be synthesised
NO
how are essential fatty acids obtained
Obtained from diet
what are the functions of essential fatty acids
- cell membrane formation
- required for proper growth and development
- required for brain and nerve function
what are essential fatty acids a precursor of
- Eicosanoids
- Prostanoids
- Leukotrienes
what does omega-6 fatty acid lower regarding CV risk
may lower LDL and HDL
What are the key regulators of lipid metabolism
Insulin and noradrenaline
What effect does insulin have on lipid metabolism
INSULIN GETS LIPID TO BE STORED
stimulates FA synthesis, TAG synthesis
suppresses lipolysis
what effect does noradrenaline have on lipid metabolism
stimulates lipolysis
What does insulin stimulate
- GLUT 4 mediated transport of glucose
- ACC activity- acetyl choline carboxylase
- Increases expression of FAS
- Increases activity of LPL in adipose (Increased uptake of lipids from circulating TGs)
active in fed state- stimulating storage
what does noradrenaline stimulate
- cAMP synthesis
- cAMP dependent (PKA) activation
- PKA mediated phosphorylation and activation of HSL
Goal: stimulate hormone sensitive lipase to breakdown TG stores
active in fasted state
How does insulin inhibits lipolysis
Doesnt inhibit lipolysis directly
Insulin stimulates breakdown of cAMP- inhibition of activation of hormone sensitive lipase
How does the regulation of LPL by insulin differ in muscles and adipocytes in fed and fasted state
FED state:
- Adipocytes: LPL synthesis increase
- Muscle: LPL synthesis decrease
FASTED state:
- Adipocytes: LPL synthesis decrease
- Muscle: LPL synthesis increase
