Lipids Flashcards
Classes of lipids
FATTY ACID DERIVATIVES
- fatty acids - fuel molecules
- Triacylglycerols - fuel storage and insulation
- phospholipids - membranes and plasma lipoproteins
- eicosanoids - local mediators that generate a response
HYDROXY-METHYL-GLUTARIC ACID DERIVATIVES
- ketone bodies - water soluble fuel molecules (during starvation brain uses)
- cholesterol - membranes and steriod hormones
- cholesterol esters - cholesterol storage
- bile acids and salts - lipid digestion
VITAMINS
- ADEK
Triacylglycerols
TAG
3 fatty acid side chains with a glycerol backbone
- are hydrophobic so are stored in their anhydrous form in adipose tissue
- utilised in prolonged exercise, starvation, during pregnancy
- storage/utilisation is under hormonal control
TAG metabolism
GI TRACT (extracellular hydrolysis of lipids in the small intestine by pancreatic lipase)
- glycerol
- fatty acids
BLOOD
- glycerol
- chylomicrons (repackaged in the small intestine into a fat globule surrounded by a membrane with proteins)
TISSUES (not Brain, cells must have mitochondria)
- glycerol goes to liver
- chylomicrons go to adipose tissue (when needed goes back into blood as fatty acids for use in the muscles)
Fatty acids
TAG/FA cycle is in a dynamic state
Converted back to TAG in the GI tract
- packaged into lipoprotein particles - chylomicrons
- released into circulation via lymphatics
- carried to adipose tissue and TAG
- released as FA when needed
- carried to tissues as albumin - fatty acid complex
Fatty acids
- saturated or unsaturated (C=C)
- amphipathic
- certain polyunsaturated FA are essential because mammals cannot introduce a double bond beyond C9 e.g. linolenic acid
Carnitine shuttle
FA is activated by ATP and linked to Coenzyme A (from vitamin B) outside of the Mitochondrion with CAT1 enzyme. Fatty acyl-CoA synthase transported across the inner mitochondrial membrane using a carnitine shuttle.
Regulated so controls the rate of FA oxidation.
- inhibited by malonyl~CoA (a Biosynthetic intermediate)
- defects can occur in the transport system - cannot switch to FA metabolism - leads to exercise intolerance and lipid droplets in muscles
Beta oxidation
FA catabolism
FA cycles through a sequence of oxidative reactions with 2 Cs (acetyl CoA) removed in each cycle
- happens in the mitochondria MUST BE AEROBIC
For a 6C fatty acid = 41 ATP (from the acetyl CoA entering the TCA) compared to 32 with 6C glucose
Glycerol metabolism
Transported in the blood to the liver where it is metabolised
- activated by ATP with glycerol kinase to make glycerol phosphate
- either goes to TAC synthesis or
- is oxidised to dihydroxyacetone phosphate (DHAP) which then enters glycolysis
Acetyl CoA
THE MAIN CONVERGENCE POINT FOR CATABOLIC PATHWAYS
- CoA contains vitamin B5 - panthenoic acid
- an important intermediate in both catabolic and anabolic pathways
Ketone bodies
can be synthesised by liver mitochondria
- acetoacetate LIVER which spontaneously decarboxylates to
- acetone (fruity smell on breath)
- beta-hydroxybutyrate LIVER
Normal plasma ketone concentration 10mM
Control of ketone body production in the liver
Acetyl-CoA is diverted from the TCA cycle to produce ketone bodies. This happens in the liver mitochondria
Statin drugs prevent the conversion of HMG-CoA to mevalonate and then cholesterol
- ketone body synthesis is regulated by the insulin/glucagon ration: fed state.
When high: lyase is inhibited and reductase is activated –> cholesterol synthesis
When low: lyase is activated and reductase is inhibited –> ketone body synthesis
Ketone bodies in starvation
Ketone bodies are used instead of glucose during starvation - saves the glucose for the CNS
Lipids
- structurally diverse
- hydrophobic - insoluble in water
- most contain only CHO but phospholipids contain PN
- more reduced than carbohydrates = more reducing power = release more energy when oxidised (requires more O2)
