Lipid metabolism Flashcards
What are the three classes of lipids
- fatty acid derivative
- hydroxy-methyl-glutaric acid
- vitamins
what types of lipids are fatty acid derivatives
- fatty acids
- triacylglycerols
- phospholipids
- eicosanoids
what types of lipids are hydroxy-methyl-glutaric acids
- ketone bodies
- cholesterol
- cholesterol esters
- bile acids and salts
what type of vitamins are lipid soluble
A
D
E
K
what and where is the first stage of lipid metabolism
extracellular digestion in GI tract
how are triacylglycerols first metabolised in the GI tract
- hydrolysed by pancreatic lipase in small intestine
broken into glycerol and fatty acids
(requires bile salts and protein factor colipase)
after triacylglycerols are broken into glycerol and fatty acids where does the glycerol go
enters blood to liver to be metabolised
how does the liver metabolise glycerol
- phosphorylated by glycerol kinase to glycerol phosphate which can either be used for triacylglycerol synthesis or enter glycolysis by converting DHAP
How are triacylglycerols stored
- converted to triacylglycerol in GI
- packed into lipoprotein particle called chylomicrons
- travel through lymphatics to adipose tissue where stored
What is lipolysis
the release of lipids from storage when needed
- hormone controlled
- stimulated by high adrenaline and glucagon
- inhibited by insulin
How are lipids released from lipolysis carries to tissues
by blood covalently bound to albumin= albumin-fatty acid complex
What are the three stages of fatty acid metabolism
1) activation
2) transport to mitochondria
3) b- oxidation
How are fatty acids activated for metabolism
by linking to CoA via S atom forming high energy hydrolysis bond
via enzyme: fatty acyl CoA synthase
How are fatty acids transported to the mitochondria
via carnitine shuttle
Why do fatty acids require a carnitine shuttle for transport to mitochondria
activated fatty acids do not readily cross inner membrane of mitochondria
Describe the action of the carnitine shuttle
- acyl group transferred to carnitine by CAT1 (carnitine acyltransferases 1) which then moves across the mem
- acyl group from acyl carnitine transferred to CoA on inside using CAT2
how is the transport of fatty acids to mitochondria regulated
- AMP and insulin
-inhibited by malonyl CoA (intermediate of FA synthesis) as means new FA made do not go directly to mitochondria
Describe the process of beta oxidation
- a spiral that removes a C2 unit (acetate) each time until only 2C remain which are all bound to CoA to make acetyl CoA
What molecules does beta oxidation require
- FAD
- NAD
- O2
What are the features of triacylglycerols
- hydrophobic
- stored in anhydrous form (no water weight)
- stored in adipose tissue
- used in exercise, starvation and pregnancy
What are the three ketone bodies produced in the body
-acetoacetate
- acetone
- B- hydroxybutyrate
what are features of ketone bodies
- soluble in water
- produced when acetyl CoA is high
- used by muscle
- alternative fuel to glucose in brain as can cross blood brain barrier
Where are ketone bodies synthesised
liver
What does the first enzyme do in ketone body synthesis do
Enzyme : synthase
function: converts acetyl CoA to Hydroxymethyl glutaryl-CoA (HMG-CoA)
What can HMG-CoA be converted
- to ketone bodies by enzyme lyase
HMG-CoA –> acetoacetate which can either degrade into acetone or be converted to beta-hydroxybutyrate - to cholesterol via enzyme HMG - CoA reductase
What enzyme do statin drugs target
HMG - CoA reductase
how is synthesis of ketone bodies controlled
controlled by inhibition of TCA cycle so acetyl CoA diverted to ketone synthesis
- low NAD or high NADH enzymes of TCA cycle inhibited so acetyl CoA diverted
How are ketone bodies synthesised
acetoacetate enters blood and is converted to acetoacetyl in muscle as is a intermediate of TCA
how is ketone synthesis regulated in the fed state
- fed means high insulin so inhibits lyase and reductase activated so cholesterol synthesis
how is ketone synthesis regulated in the early starvation state
- starvation means low insulin and high glucagon
- lyase activated and reducatase inhibited so ketone synthesis
how do ketone bodies spare glucose
reserve glucose for brain and other tissues use ketone bodies
how do ketone bodies spare glucose in late starvation
- very low insulin
- ketones produced for all other tissues but glucose for brain from breakdown of muscle and glycogen
what happens in diabetes with ketone production and glucose
- high glucose as not being utlilised
- ketone bodies still being produced as glucose not used so uncontrolled ketogenesis
what are the plasma levels of ketones in the normal state
less than 1nm
what are the plasma levels of ketones in the starvation state
2-5nm (physiological ketosis)
what are the plasma levels of ketones in diabetes
greater than 10m (pathological ketosis)
