Lipid metabolism and pathways Flashcards
List the biological functions of lipids
Essential components of cell membranes e.g. phospholipids, glycolipids, cholesterol
Energy generation and storage i.e. triglycerides
Inter- and Intra-cellular signalling events e.g. precursor of steroid hormones
Metabolism e.g. bile acids
What are metabolites?
The reactants, intermediates and products of a Series of connected enzymatic reactions that produce specific products
Describe the 2 major steps in the digestion of dietary TGs
TGs need to be first EMULSIFIED by BILE ACIDS; (bile acids are detergent-like molecules)
TGs are then HYDROLYSED by the enzyme PANCREATIC TRIACYLGLYCEROL LIPASE
What are the products of fat digestion?
Mixture of fatty acids and mono-and diacylglycerols
What are the 2 major metabolism pathways of lipids?
Oxidation in the mitochondria to release energy in the form of ATP
Synthesis of TG from acetyl-CoA (for storage)
Describe the process of oxidation of triglycerides
Oxidation of long chain fatty acids to 2-carbon fragments in the form of acetyl-CoA: THIS IS β-OXIDATION
Oxidation of acetyl-CoA to CO2 in the citric acid cycle
Transfer of electrons from reduced electron carriers to mitochondrial respiratory chain
What is beta oxidation?
Successive removal of 2-carbon fragments from fatty acids
Where does beta oxidation occur?
Occurs in mitochondria, also in peroxisomes
Describe the process of beta oxidation
1st step: fatty acids activated by attachment to Coenzyme A (CYTOSOL)
2nd step: transfer of acyl-CoA across mitochondrial membrane (RATE-LIMITING STEP)
3rd step: progressive oxidation of fatty acids by removal of 2-carbon units to form acetyl-CoA which enters the citric acid cycle
What is formed after each cycle of beta oxidation?
Each cycle: Shorten by 2C 1 acetyl-CoA formed 1 FADH2 formed 1 NADH formed
Where does fatty acid synthesis occur?
In the liver and adipocytes
Occurs in the cytosol of the cells
What occurs during fatty acid synthesis?
Long chain carbon molecules built up from 2-carbon units derived from acetyl CoA
Where is acetyl CoA found?
In the mitochondria
How does the acetyl CoA get out of the mitochondria and into the cytosol?
Via Citrate malate cycle
Acetyl CoA is converted to citrate which can be then converted back to Acetyl CoA in the cytosol
Describe the rate limiting steps
Rate-limiting steps:
β-oxidation: transfer of acyl-CoA into mitochondria
Fatty acid synthesis: formation of malonyl CoA from acetyl-CoA, catalysed by acetyl CoA carboxylase
Describe fatty acid synthesis
Malonyl CoA and acetyl CoA both bind to fatty acid synthase
A series of condensation reactions involving malonyl CoA adds further C2 units
Where is cholesterol synthesised and eliminated?
Synthesized from acetyl CoA and eliminated as bile acids
Where is cholesterol stored?
Amphipathic lipid (hydrophobic and hydrophilic portions) storage form is cholesterol ester found in most tissues
List the physiological roles of cholesterol
Important lipid component of biological membranes,
Precursor of steroid hormones
Source of bile acids
What do bile acids aid?
lipid digestion
lipid absorption
cholesterol excretion
What are bile acids?
Cholesterol derivatives
What are bile acids?
Cholesterol polar derivatives
Describe cholesterol in health
Essential for life
Bad in excess
In healthy organism, balance maintained between biosynthesis, utilisation and transport – keeping harmful deposition to a minimum
What does HMG-CoA reductase do?
Catalyses the conversion of acetyl CoA to mevalonate
Why is HMG-CoA important?
Rate determining step
Cholesterol is feedback inhibitor
Mevalonate is feedback inhibitor
Target for statin drugs
What are statins and how do they work?
Statins are competitive inhibitors of HMG-CoA reductase. They are bulky and literally get “stuck” in the active site
This prevents the enzyme from binding with its substrate, HMG-CoA
Describe the 2 classes of statins
Natural Statins: Lovastatin (mevacor), Compactin, Pravastatin (pravachol), Simvastatin (Zocor).
Synthetic Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol)
Why is lipid transport around the body important?
Bring dietary lipids to cells for energy production or storage
Provide lipids from the diet to cells for synthesizing cell membranes
Move lipids from storage in adipose tissue for use in energy production
Carry cholesterol from peripheral tissues to the liver for excretion
How are short chain fatty acids transported in the body?
Short-chain fatty acids are transported bound to blood proteins like albumin
How are the bulk of lipids transported around the body?
Bulk transport of neutral lipids, which are insoluble in water, requires special carrier proteins: lipoproteins
What are lipoproteins composed of?
Lipoproteins are composed of hydrophilic, hydrophobic and amphipathic molecules
Describe the structure of lipoproteins
In addition to the lipids carried in a central core, the outer layer of amphipathic phospholipids contains cholesterol, and has proteins called apolipoproteins associated with it.
Give a summary of lipid transport
Chylomicrons: deliver dietary TGs to muscle and adipose tissue + dietary cholesterol to the liver
VLDL: transport endogenous TGs and cholesterol
LDL: transport cholesterol from liver to tissues
HDL: transport cholesterol from tissues to liver i.e. remove cholesterol from tissues- reverse transport
Where is most cholesterol carried?
LDL
some in HDL
What does VLDL become when it unloads some lipid?
IDL and then LDL in cases where lots of lipid is unloaded
What are VLDL,IDL, LDL used for?
From liver to periphery
What is HDL used for?
Reverse transport
What is the importance of tissue bound lipoprotein lipase?
Allows release of triglycerides at the tissues
How does the liver uptake the particles?
The liver recognises remnants of these particles by their ApoE content, and takes them up for re-cycling
How is LDL uptaken?
LDL particles contain ApoB-100, which is recognised by cell surface LDL receptors
What causes degradation of LDLR?
PCSK9 binds to LDL receptor and results in it’s degradation
Uptake of cholesterol results in…
A decrease in cholesterol synthesis
