Lipid Metabolism Flashcards
List the dietary lipids
- Triglycerides
- Cholesterol
- Phospholipids
List the different types of FAs in triglycertides
- Saturated (no-double bonds - usually solid at RT)
- Monounsaturated (1 double bond - liquid)
- Polyunsaturated (>1 double bond - liquid)
*the H
Structure of tryglycerides
Glycerol attached to 3 FA chains via ESTER BOND
Where does lipid digestion occur?
Small intestine
What enzymes digest lipids?
Pancreatic lipase and co-lipase
Enzymes also require bile salts which are formed from cholesterol; stored and secreted from the gall bladder and emulsify the large lipid droplet to smaller lipid droplets
What does the digestion of lipid yield?
triglyceride –> monoglyceride + 2FAs
How are lipids absorbed?
- Micelles breakdown forming FAs and MG at the apical surfaces of enterocytes
- Diffusion
- Triacytlglycerol (TAG) packaged with cholesterol, phospholipids, and others forming chylomicrons
- Chylomicrons are released into lymphatic system by exocytosis (into lacteal to thoracic duct into venous system)
How are lipids transported in the plasma after absorption?
- Chylomicron binds to lipoprotein lipase
What is the fate of lipids absorbed?
- Storage - TAG
- Structural - phospholipid membrane bilayer
- Oxidation - ATP
How are lipids taken up by cells?
Via LDLrs
Low density lipoprotein receptors
How is fat-metabolised?
Beta-oxidation
- Generation of ATP (energy) from FFAs
- Oxidation of the beta-carbon (C3) facilitates sequential cleavage of acetyl units
What is beta-oxidation
Where does it occur?
- Generation of ATP from FFAs
- FAs first added to acetyl CoA to form fatty acytl-CoA
- Occurs in the mitochondria
Therefore it must cross the inner mitochondrial membrane via carnitine (carrier molecule)
What is carnitine?
Carrier molecule
Carries FFA into mitochondria
Derived from lysine and methionine
High in muscle
Where is CPT I located?
Outer mitochondrial membrane
Where is CPT II located?
Inner mitochondria membrane
What does CPT stand form?
Carnitine Palmitoyl Transferase
What does B-oxidation yield?
FADH2
NADH
Acetyl CoA (2C)
Ends up with final Acetyl CoA —> ATP
(TCA cycle/oxidative phosphorylation)
How many C-atoms are oxidised at a time?
2
How much is the ATP yield of palmitate (C16)
106ATP
What is triglyceride synthesis?
Esterification of 3FAs and glycerol
What are the intermediates and regulated enzymes of triglyceride synthesis in adipose tissue?
- Esterification of 3FAs + glycerol
- Lipoprotein lipase (LPL) hydrolyses TAG in chylomicroms
- Diacylglycerol Acyl Transferase (DGAT) re-esterifies to TAG
- Glycerol obtained from glycolysis
What are the 2 enzymes involved in triglyceride synthesis?
Lipoportein lipase (on surface) DGAT (inside cell)
What are intermediates and regulated enzymes of lipolysis in adipose tissue?
Lipolysis = Triglyceride breakdown of triglycertide into glycerol and 3FAs
- Hormone sensitive lipase in adipose tissue
What is hormone sensitive lipase and how is it activated?
HSL is involved in lipolysis
It is activated by cAMP-dependent phosphorylation in response to adrenaline in the fasted state
What inhibits hormone sensitive lipase?
Insulin
What triggers hormone sensitive lipase activity?
Adrenaline
Describe the key intermediates and regulated enzymes of fatty acid synthesis
Stage 1: formation of precursor malonyl CoA by acetyl CoA carboxylase and biotin from acetyle CoA
Stage 2: coupling acetyl CoA to malonyl CoA elongation of chain 2Cs at a time by fatty acid synthase
- requires NADPH via pentose phosphate pathway
- 7 steps
What is the significance of malonyl CoA?
Inhibits carnitine palmitoyl transferase (CPT) thus inhibiting FA b-oxidation
Where does FA synthesis takes place?
Cytoplasm
Where does FA oxidation takes place?
Mitochondria
What is the product of b-oxidation?
Acetyl CoA
How are ketone bodies formed from FA oxidation?
- b-oxidation forms acetyl CoA
- acetyl CoA enters Krebs
HOWEVERE
if oxaloacetate is NOT present then acetyl CoA is converted into ketone bodies
Ketone bodies are essentially and OVERFLOW of acetyl CoA
- they start joining together
acetyl-CoA + acetyl-CoA = acetoacetyl CoA
acetoacetyl CoA - CoA = acetoacetate
Acetoacetate can be converted into acetone or/and hydroxybutyrate
Describe the formation of phospholipids
Same as triglyceride synthesis
Then combine with alcohol
Where do you find high levels of phospholipid synthesis?
Rapidly dividing cells
Explain the requirements for essential fatty acids
- Cannot be synthesised
- Must be obtained from diet
- Polyunsaturated omega 3 and 6
What are the functions of essential FAs
- Cell membrane function
- Required for proper growth and development
- Required for brain and nerve function
- Precursors for inflammatory mediators
What are the key regulators of lipid metabolism?
Insulin - inhibits
Adrenaline - triggers
How does insulin regulate lipid metabolism?
Stimulates FA and TAG synthesis
Suppresses lipolysis
How does insulin suppress lipolysis?
Inhibits hormone sensitive lipase
What does adrenaline do in lipid metabolism?
Stimulates lipolysis via hormone sensitive lipase
Outline what insulin does during lipid metabolism
IN THE FED STATE
- GLUT4 translocation
- Activates acetyl CoA Carboxylase (FA synthesis first step)
- Increases expression of FA synthase (FA synthesis 2nd step)
- Increases activity of lipoprotein lipase
Outline what adrenaline does during lipid metabolism
- cAMP synthesis
- cAMP-dependent phosphorylation of PKA
- cAMP-PKA phosphorylation and activation of hormone sensitive lipase (HSL)
What does insulin do to lipolysis?
Inhibits lipolysis by stimulating the breakdown of cAMP
Describe the regulation of lipoprotein lipase
Lipoprotein lipase breakdown chylomicrons into FAs
Expressed on the cell surface
In the fed state:
- LPL synthesis and activity is increased on adipocyte
- LPL synthesis and activity is decreased on muscle and liver
In the fasting state:
- LPL synthesis and activity decreases on adipocytes
- LPL synthesis and activity increases on muscle and liver
