Lipids Flashcards
Lipid Structure Facts
- Structurally diverse
- Generally insoluble in water (hydrophobic)
- Most only contain C, H, O – (phospholipids contain P, N)
- More reduced than carbohydrates
– release more energy when oxidised – complete oxidation requires more O2
Structure of fatty acids
Alaphatic chain od methyl groups with acid (carboxylic) group on one end
What are the types of lipids
Fatty acids, triacylglycerols and ketone bodies are the types of lipid used as fuel molecules.
How are lipids stored
Triacylglycerol
What is the structure of Triacylglycerol
Glycerol backbone attached to three fatty acids
How are ketone bodies formed
In the liver fatty acids are turned in to ketone bodies
Derived from fatty acids
What is derived from Fatty Acids
Fatty acids - Fuel molecules
Triacylglycerols (Triglycerides) - Fuel Storage and insulation
Phospholipids – components of membranes and plasma
lipoproteins
Eicosanoids – local mediators (signaling molecules)
What is derived from Hydroxy-methyl-glutaric acid derivatives (C6 compound)
Kentone Bodies (C4) - Water soluble fuel molecules
Cholesterol (C27) – membranes (fluidity) and steroid hormone synthesis
Cholesterol esters – cholesterol storage
Bile acids and salts (C24) – lipid digestion
What are the fat soluble vitamins
A, D, E and K.
derived from lipids
Does Triacylglycerols Glycogen Muscle protein vary with heathy to obese people
Glycogen and Muscle protein remain constant
Triacylglycerols go up with from heathy to obese by the weight increase
What is Triacylglycerols derived from
Glycerol and Fatty acids in an esterification reaction
What is Lipolysis
Triacylglycerols turning back in to Glycerol and fatty acids
Function of Triacylglycerols,
Is it hydrophobic or hydrophilic
- Triacylglycerols are hydrophobic
- Therefore stored in ananhydrous form
- Stored in specialised tissue– adipose tissue
- Utilised in prolonged exercise, ‘starvation’,
and also during pregnancy - Storage/ mobilisation is under tight hormonal control
what is the benefit of Tricylglyerols being hydrophobic
As its in an Anhydrous form
When stored they can hold alot more fuel per gram of weight
When and where does Metabolism of triacylglycerols occur
- Stage 1
- GI Tract (lumen) (Small interstine)
- Extracellular
What happens to fatty acids after metabolism of triacylglycerols (in to fatty acids and Glycerol)
- Converted back to triglycerides in G.I. tract in the cells
- Packaged into lipoprotein particle ( this stabilises them as they interact with many other pathways eg, amino acid pathway)
- The packages are called CHYLOMICRONS
- Released into circulation via lymphatics
- Carried to adipose tissue
- Stored as triglyceride (triacylglycerols)
- Released as fatty acids when needed
- Carried to tissues as albumin-fatty acid complex ( different transport process as lipids aren’t water soluble)
What is the colour when you disect the lymphatics
Looks milky due to the CHYLOMICRONS
Fatty Acid Catabolism - Summary
- FA is activated (by linking to coenzyme A outside the mitochondrion)
- Transported across the inner mitochondrial membrane using a carnitine shuttle
- FA cycles through sequences of oxidative reactions, with C2 removed each cycle
(C18 —> C16 + C2)
How is fatty acid Activated
Occurs outside the mitochondria, in cytoplasm
- Fatty acids activated by linking to coenzyme A
(via high energy bond) by the action of fatty acyl CoA synthase :
CH3(CH2)nCOOH (FATTY ACID) + ATP + CoA —> CH3(CH2)nCO~CoA (fatty acyl~CoA) + AMP + 2Pi
How are fatty acyl~CoA transported
Activated fatty acids (fatty acyl~CoA) do not readily cross the inner mitochondrial membrane
thus
Carnitine shuttle transports fatty acyl~CoA across the mitochondrial membrane
How does the Carnitine Shuttle work
- Acyl Coa is put on to the carnitine making it Acl Carnitine using Carnitine acyltransferases 1
- Carnitie shuttle swaps Acyl carnitine for carnitine across membrane
- Acyl transferred back on to the CoA again using
Carnitine acyltransferases 2
What does Carnitine acyltransferases do
Puts Acyl group onto Carnitine and helps move it across membrane
How is Carnitine shuttle transport regulated
- Regulated (AMP, insulin), so controls the rate of FA oxidation
- CAT1 inhibited by malonyl~CoA (biosynthetic intermediate)
- Defects can occur in this transport system (exercise intolerance, lipid droplets in muscle)
Why is called Beta - Oxidation
As its the Beta Carbon that gets oxidised
What is the final step of B-oxidation
CO.CH2.CO-CoA gets cleaved and and addition of CoA to form CO-CoA + CH3.CO-CoA
What is ultimately produced by B-oxidation and what are they used for
β-oxidation ultimately generates acetyl CoA and reducing power.
These intermediates are used to generate ATP in stages 3 and 4 of catabolism
Where does B-Oxidation occur
Most tissues and white blood cells
DOESNT OCCUR IN BRAIN as fatty acids can’t get though brain barrier
Doesn’t occur in RBC as there is no mitochondria
Fatty acid and glycerol metabolism
(B-oxidation)
(8) - Key Points
- Mitochondrial
- Cycle of reactions
- Removal of 2C units per cycle
- β-carbon oxidation
- H+ and e- transferred to NAD+ and FAD
- Stops in absence of O2
- Regulated by AMP (insulin – liver)
- No direct ATP synthesis
What happens to glycerol
Glycerol can be transported in the blood to the liver, where it is metabolised
By Glycerol kinase using ATP
forming
Glycerol phosphate
What happens to Glycerol phosphate
There are two pathways
It can enter glycolysis, using
glycerol 3-phosphate dehydrogenase
It will create Dihydroxyacetone - P
or
It can be stored as Fat (triacylglycerol)
This requires fatty acids
Where and How ketone bodies generated
The liver mitochondria constantly generates ketone bodies from acetyl CoA
Adipose tissue release fatty acids
liver sensors pick this up
Thus generates Ketone bodies
Produced when Acetyl CoA is in excess
When is the production of ketone bodies higher
Production is much higher during fasting (and starvation)
What are Kentone bodies used for
- Used by peripheral tissues (muscle)
- Alternative fuel to glucose
(helps conserve glucose)
Why is ketone bodies an important energy source
They are water soluble
(whilst fatty acids are NOT thus finite amount of fatty acids can be transported)
Thus provided more fuel molecules
What is the pKA of kentones
What is Physiological ketosis
acidic – pKa ~4 (deporotonated) making blood ph more acidic
Blood becomes more acidic due to higher ketone conc
What is the Normal Plasma ketone conc
Normal plasma ketone body concentration < 1 mM
What is the Starvation, Ketones conc
Starvation 2-10 mM (physiological ketosis)
What happens in untreated Type 1 diabetes
Untreated Type 1 diabetes > 10 mM (pathological ketosis)
What are the steps in ketone production
1.Acetly CoA (CH3CO-CoA) is sythesised in to
2.Hydroxymethyl glutaryl-CoA. (HMG-CoA) which is lysed by the enzyme lyase in to
3. acetoacetate and β-hdroxybutyrate these are used as biological fuels
What happens when Hydroxymethyl glutaryl-CoA.
(HMG-CoA) interacts with HMG-CoA
Reductase (staitin drug)
When the insulin/glucagon ratio is high
Mevalonate —> Cholesterol occurs when
When the insulin/glucagon ratio is high, i.e. fed state:
Lyase is inhibited+reductase activated –> cholesterol synthesis
Control of Ketone body production in the liver
1.Triacyglycerols levels get high
2. Fatty acids levels thus rise
3. Low NAD+ substrate
4. High NADH
5. This inhibits the TCA cycle
6. Thus acetyl-CoA gets diverted to produce Ketone Bodies
What happens to Acetoacetate
Acetoacetate -
Acetone-
Acetoacetate - (using Sunccinyl CoA) turns to
Acetoacetyl CoA - Then another CoA added to form
Acetyl CoA (x2)- which is used in the TCA cycle
Which is used to generate ATP
What happens when the insulin/glucagon ratio is Low
When the insulin/glucagon ratio is Low, i.e. starvation state: Lyase is activated + reductase inhibited ketone body
What happens in Starvation / Diabetes
Ketone bodies gets used preferably rather than glucose
glucose only used by cells that need it eg brain
Diabetes this is uncontrolled
all systems switched on
blood glucose is very high
Ketone levels gets very high
no insulin generated
no brake mechanism
Kentone lavels build up
leads to Ketoacidosis / Ketosis
Blood Ph becomes acidic
Can damage brain
Leads to coma and can even Die
Given Insulin to bring all process back under control
lowers glucose and ketone levels.
What Is the role of Acetyl CoA in metabolism
Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.
