Metabolic pathways: Lipid catabolism Flashcards
Why is lipid metabolism important?
It is associated with human disease
What are essential fatty acids?
Body cannot produce them
Deficiencies can lead to membrane disorders, increased skin permeability, mitochondrial damage
What are the fat soluble vitamins?
A
D
E
k
What are simple lipids?
Fatty acids, triglycerides, waxes
What are compound lipids/
Phospho- glyco-lippids, lipoproteins
What are steroids
Cholesterol, steroid hormones
Are lipids soluble in water?
NO
Why are triglycerides important?
Main energy storage form in adipose tissue
Compact
-dont require concomitant storage of water
What do triglycerides consist of?
Glycerol and three fatty acids
How are esters and fatty acids linked?
Ester linkage
What is the structure of fatty acids?
Straight chained
Alipathic- no rings
Even number of C atoms
Some are branches and have odd numbers
- Saturated
- Unsaturated
- Polyunsaturated
What is the configuration double bonds in the fatty acid chains?
Cis configuration- chain continues in the same direction from the double bond (left and right below the double bond)
Trans- two side chains are at opposing sides of the double bond
Where is cis configuration found?
Naturally occurring fats
Why are polyunsaturated fatty acids important?
Essential
Cannot be synthesised
What is an omega three fatty acid?
A fatty acid with a double bond three carbons away from its omega carbon
What is an omega carbon
The last carbon
Which carbons are liquid at room temperature?
Carbons with up to 8C, longer ones are solid
Do double bonds increase the melting point?
No they decrease it
Why are plant fats liquid?
They have large proportions of unsaturated fatty acids
Why are animal fats solid?
Contain mostly palmitic and stearic acid
What does digestion of fats produce?
Glycerol
Fatty acids
Mono-glycerides
Where do products of fat digestion go?
Absorbed into mucosal cells of intestine
What happens to short and medium length fatty acids?
Enter portal blood
What happened to longer chain FAs and monoglycerides?
Resynthesised to triglycerides which are coated with proteins, phospholipids and cholesterol forming chlyomicrons which enter lymph and then bloodstream
What happens to chylomicrons within muscle and adipose tissue?
Attacked and cleaved by lipoprotein lipase
What happens to free fatty acids at adipose tissue?
Resynthesised to triaglycerols for storage
What happens to free fatty acids in muscle?
Oxidised to produce energy
What does oxidation of fatty acids depend upon?
How many fatty acids are available
What happens to stored fat during times of starvation?
Broken down in lipolysis by hormone sensitive lipases
What does initial cleavage by hormone sensitive lipase cause?
Release of free fatty acids and glycerol
What happens to a fatty acid if it is required for energy?
Activated by linking to Co-enzyme A in the cytoplasm of cells (requiring 2ATP). This forms an acyl-CoA
What is the difference between acyl-CoA and acetyl CoA
Acyl-CoA= uncertain number of carbons
Acetyl-CoA= 2 carbons
What is the difficulty with fatty acid oxidation?
Acyl-CoA has to be transported from cytoplasm to mitochondrial matric
How does the carnitine shuttle work?
Acyl-CoA fatty acid is transferred onto carnitine forming acyl-carnitine which can be transported to the matric
What happens to acyl-carnitine when it reaches the matrix?
The fatty acid is cleave off again, reforming Acyl-CoA and allowing the cycle to continue
What is the net result of the carnitine shuttle?
Acyl-CoA located in mitochondrial matrix, CoA is NEVER transported across
What is B Oxidation?
Cycle of reactions in the mitochondrial matrix with Acyl-CoA as its substrate
Describe the reactions in B oxidation?
Four steps in each cycle- the acyl CoA is shortened by two carbons, producing 1 Acetyl-CoA, a shortened Acyl-CoA, 1 FADH2, 1NADH + H+
How many times will B oxidation occur in stearic acid (C18)? What are the products?
Repeated 8 times
- 8 FADH2, 8 NADH + 8H+
- 9 acetyl-CoA molecules which are oxidised to CO2 in the TCA cycle
What is the yield for 9 acetyl-CoA in the TCA cycle?
-9 FADH2, 27 NADH, 27 H + 9 GTP
What is the P/O ratio?
The amount of ATP we can obtain for the reduction of a single oxygen atom to water
What is the P/O ration of FADH2?
1.5
What is the P/O ratio of NADH + H+ ?
2.5
What oxidation reactions involve additional enzymes?
Unsaturated fatty acids
Odd-Chain fatty acids
Branched-chain fatty acids
What happens to glycerol following hydrolysis of fats?
Activated to glycerol-3-phosphate by glycerol kinase (present in liver and kidney)
Dehydrogenated to dihydroxyacetone phosphate (normal intermediate of carbohydrate metabolism)
When does the formation of ketone bodies occur normally?
In liver mitochondria from acetyl-CoA from B oxidation
What are the 3 ketones?
Acetoacetate
Acetone
a-2-hydroxybutrate
What happens to ketone bodies?
Diffuse into blood stream and to peripheral tissues
Concerted back to acetyl-CoA which enters TCA cycle
What are ketone bodies important for?
Important molecules of energy metabolism for heart muscle and renal cortex
What happens in starvation and diabetes?
Oxaloacetate is consumed for gluconeogenesis- liver produced new glucose which removes oxaloacetate.
Fatty acids are oxidised to provide energy which produces acetyl-CoA which enter the TCA cycle due to lack of oxaloacetate?
What happens to acetyl-CoA that cannot enter the TCA cycle?
Converted to ketone bodies
Why is ketone body accumulation bad?
Ketone bodies are moderate acids
Accumulation leads to severe acidosis- blood can’t buffer anymore
Impairs tissue function, particularly CNS
How can ketosis be identified?
Smell of acetone in breath
