MEH Lipid Metabolism Flashcards
What are more reduced - carbs or lipids? What does this mean for metabolism?
Lipids - require more O2 for complete oxidation
What 3 elements do most lipids contain?
C H O
What are the three classes of lipids in the body? Give examples
1) Fatty acid derivatives
Fatty acids
TAGs
2) HMG acid derivatives
Ketones
Cholesterol
Bile salts
3) Vitamines
ADEK
What is the difference between a fatty acid and a TAG?
TAGs are broken down into fatty acids and glycerol
What does anhydrous mean and what is the relevance with lipids?
Stored without water - in fat droplets in adipose tissue
What 2 substances are required apart from pancreatic lipase to break down TAG into glycerol and fatty acids?
Bile salts
A protein called colipase
When are lipids stored for?
Use in starvation, stress, pregnancy, prolonged exercise
Where is glycerol metabolised?
Liver
Can RBC use fatty acids as fuel? Why?
No as no organelles and no mito no beta-oxidation
What happens to FA after they have been broken down from TAG to FA and glycerol in the small intestine?
Reform as TAG, packed into a chylomicron, released into circulation via lymphatics, carried to adipose, stored as TAG
Is there a difference between triglyceride and TAG?
No mean same thing
What hormones is fatty acid mobilisation under control of? Which enzyme does this stimulate/inhibit?
Glucagon and adrenaline - increase hormone sensitive lipase
Insulin - inhibits
What is a chylomicron?
A lipoprotein particle that is packed with TAG (mostly), phospholipids, cholesterol and proteins
How are fatty acids carried to tissues once mobilised from adipose?
As fatty acid - albumin complexes
What intermediate is used from glycolysis to produce fatty acids? What happens when glucose is low?
Glycerol 1P —> enables TAG synthesis (backbone). Low glucose prevents glycerol 1P from entering the fatty acid cycle in adipose tissue and so fatty acids are released as they aren’t bound to glycerol (no backbone made)
What three things occur in FA catabolism?
Activation
Carnitine Shuttle
Beta-oxidation
What is Fatty acid activation? What enzyme?
FA have to be activated before being oxidised. Activated by linking to coenzyme A to form fatty acyl co A (fatty acyl coA synthase)
Why do we need a carnitine shuttle? What does it do? What enzymes?
Fatty acyl co A cannot readily cross inner mito membrane so needs transporting. used CAT 1 and CAT 2 enzymes.
Does fatty acid activation control the rate of FA oxidation? How is it inhibited?
Yes as it is regulated so controls rate.
Is inhibited by malonyl co A (a biosynthetic intermediate)
What defects can occur with fatty acid activation?
Exercise intolerance
Fatty acid droplets in muscle
What happens after FA activation and where?
In mito matrix - beta oxidation
Are all FA intermediates linked to coA or just FA?
All intermediates
What is FA beta oxidation? Does FA metabolism release more or less energy than glucose metabolism?
A series of oxidative reactions that release C2 with each cycle. Releases more energy than glucose
Does beta oxidation happen in all tissues? Why?
No most - as requires oxygen so not in some tissues e.g. RBC, WBC, brain
In beta oxidation - where do the electrons go? Is ATP produced directly? What happens with no O2?
To FAD and NAD+ to form FADH2 and NADH
No ATP made
Stops with no O2
What 2 things can glycerol be used for when metabolised?
- TAG synthesis
- Glycolysis
What enzyme converts glycerol into glycerol phosphate
Glycerol Kinase
Where does glycerol metabolism occur?
Liver
What is the most important intermediate for all metabolic pathways? Which 2 lipid biosynthetic pathways can it be used for?
Acetyl co A
To make FA –> TAGs/Phospholipids
To make HMG derivatives - cholesterol/ketone bodies
What are the three ketones produced in the body?
Acetone
Acetoacetate
beta- hydroxybutyrate
From glycerol phosphate to DHAP oxidation reaction where does the e-/H+ go?
to NAD+ to form NADH
Why is acetyl co A called ‘activated acetyl group’
Because it has a high energy bond between the carbon group and co enzyme A - linked with S atom
What vitamin does coA contain?
B5
How does acetoacetate form acetone?
Decarboxylation - one of few non-enzyme reactions that goes on in body - occurs in the liver
Are ketones water soluble or lipid soluble? What does this mean for their transportation in the blood?
Water soluble so don’t need carrier proteins
What happens after beta oxidation in normal metabolism?
Acetyl co A and FADH2 and NADH are formed. Acetyl co A goes onto stage 3 metabolism –> TCA cycle, FADH2 and NADH are used for stage 4 oxidative phosphorylation.
What happens after beta oxidation in starved state (i.e. high glucagon, low insulin, low glucose?)
Acetyl co A is redirected to make ketone bodies
How are ketone bodies made from acetyl co A (8 steps)?
1) Low glucose stimulates FA mobilisation
2) FA metabolism creates NADH and FADH2 - high energy signals
3) These high energy signals inhibit 2 enzymes in the TCA cycle (alpha-ketoglutarate dehydrogenase, isocitrate dehydrogenase)
4) This prevents the formation of oxaloacetate feeding back into the TCA cycle with acetyl co A
5) Acetyl co A builds up
6) Lyase is activated, HMG coA reductase is inhibited
7) Acetyl co A —> HMG co A by synthase
8) HMG co A —> ketones by lyase
What happens after beta oxidation in fed state? (i.e. high insulin, high sugar, low glucagon)
Acetyl co A is diverted to make cholesterol
How is cholesterol made from acetyl co A?
1) If TCA cycle overwhelmed with acetyl co A –> build up
2) Synthase converted to HMG co A
3) Fed state stimulates HMG co A reductase and inhibits lyase
4) HMG-co A to mevalonate with HMG co A reductase
5) Mevaolonate forms cholesterol
What is the use of ketone bodies?
Ketone bodies can be converted back to acetyl co A by the liver and used in other tissues via TCA cycle to produce energy. This spares the glucose for the brain
What happens in late starvation with ketone bodies/proteins?
Ketone bodies are formed for energy.
Protein is also broken down to amino acids –> pyruvate and pyruvate can undergo gluconeogenesis via an alternative route. This can then be used to supply the brain
What is ketonuria and why does it occur?
Ketones in urine due to the level of ketones being above the renal threshold —> see in diabetes and ketoacidosis
How else may ketones (acetone) be excreted from the body other than the kidney?
Via the lungs
