Cellular Metabolism 2- Lipids (2) Flashcards
Where is acetyl coA generated by fatty acids?
in mitochondria
What are the 3 primary sources of fat?
- diet
- liver de novo biosynthesis
- storage deposits in adipose tissue
What is the result of a lack of bile salts?
majority of fat passes through gut undigested and unabsorbed, resulting in steatorrhea (fatty stool)
What is Orlistat (tetrahydrolipstatin)?
- potent inhibitor of gastric and pancreatic lipases
- reduces fat absorption by 30%- excreted by faecal route
- treatment for obesity, but causes abdominal pain, urgency to defecate, flatus and steatorrhea
How are lipids transported in the plasma?
by lipoproteins- contain fatty acids w/in a core- soluble hydrophilic outer
Where are chylomicrons produced and what is their role?
- intestines
- dietary fat transport
Where are VLDLs produced and what is their role?
- liver
- endogenous (originated in liver) fat transport
Where are IDLs produced and what is their role?
- originate from VLDLs
- LDL precursor
Where are LDLs produced and what is their role?
- originate from IDLs
- cholesterol transport
Where are HDLs produced and what is their role?
- liver
- reverse cholesterol transport
What is the structure of a chylomicron?
- phospholipid monolayer
- apoproteins sat in layer
- triglycerides inside
What is lipoprotein lipase and what is its function?
- located on capillary endothelial cells lining adipose, heart and skeletal muscle tissues
- recognises apoprotein–> activates enzyme (conformational change)
- -> digests triglycerides and takes up fatty acids into cell (leaves glycerol in bloodstream)
What is the life cycle of chylomicrons?
- enterocytes make chylomicrons containing lipids
- HDL transfers apoproteins onto chylomicrons
- can be recognised by tissues and deliver FFAs
- then chylomicron remnants can get more apoproteins from HDL–> recognised by liver and taken up, reprocessed
What is the structure of a lipoprotein?
- phospholipid monolayer containing cholesterol and apoproteins
- surround a core of cholesterol esters and triglycerides
How are cholesterol esters made?
- synthesised in plasma
- cholesterol + phosphatidylcholine (donates acyl chain)
- catalysed by LCAT (lecithin:cholesterol acyltransferase)
What is the life cycle of VLDLs, IDLs, HDL, and LDLs?
- liver produces VLDLs- deliver contents to tissues
- becomes lipid-depleted remnant
- transfer of proteins from VLDL back to HDL
- becomes IDL
- cholesterol esters from HDL packaged and transferred to IDL
- becomes LDL–> uptake by liver or macrophages
(N.B. VLDL and HDL are the only ones synthesised by liver)
Why are HDLs often referred to as ‘good cholesterol’?
- they take cholesterol from peripheral tissues (dead or dying cells) back to liver for use or disposal by reverse cholesterol transport
- thus they help to lower total serum cholesterol
Why are LDLs often referred to as ‘bad cholesterol’?
- raised LDL levels leads to atherosclerosis
- transport cholesterol synthesised in liver to peripheral tissues w/ more than 40% of their weight being cholesterol esters
How does the carnitine shuttle work?
- generation of Acyl CoA species on cytoplasmic side
- carnitine acyltransferase 1 transfers acyl group from acyl coA to carnitine–> acyl carnitine
- acyl carnitine carried by translocase into mitochondrial matrix
- reverse reaction using carnitine acyltransferase 2 to produce acyl coA and carnitine- which is shuttled back out
How many beta oxidation reactions would be needed to generate 8 acetyl coA from palmitic acid (16C)?
7 rounds of beta oxidation, so 7FAD, 7NAD+, 7H2O and 7CoA used up
…7FADH2 and 7NADH produced (as well as 8 acetyl coA)
What is the initial reaction in the beta oxidation of fatty acids?
fatty acid + ATP + coA
- -> acyl coA + AMP + PPi
- firstly, fatty acids are converted to an acyl CoA species
- this reaction is coupled to the hydrolysis of ATP, but instead of going to ADP and Pi, it goes all the way to monophosphate group and PPi
What is the initial reaction in the beta oxidation of fatty acids?
fatty acid + ATP + coA
- -> acyl coA + AMP + PPi using acyl coA synthetase
- firstly, fatty acids are converted to an acyl CoA species
- this reaction is coupled to the hydrolysis of ATP, but instead of going to ADP and Pi, it goes all the way to monophosphate group and PPi
What 4 reactions occur in the beta oxidation cycle following the production of an acyl coA?
- acyl coA oxidised and FAD reduced to FADH2
- hydrated, breaking double bond
- another oxidation reaction, NAD+–> NADH
- thiolysis- molecule split up and coA displaces acetyl group from acyl coA–> results in acetyl coA (which enters TCA cycle) and an acyl coA species 2C shorter than original
What happens to acetyl coA if fat breakdown predominates?
e.g. during fasting
acetyl coA forms acetoacetate by condensation–> breaks down into acetone and D-3-hydroxybutyrate (KETONE BODIES)
What are some differences between beta oxidation and fatty acid biosynthesis?
- fatty acid biosynthesis involves only 2 enzymes: acetyl coA carboxylase and fatty acid synthase
- condensing acetyl coA w/ malonyl coA
- following each round of elongation, the fatty acid undergoes reduction and dehydration and reduction
- acyl carrier proteins vs coA
- NADPH vs FAD/NAD+
- synthesis in cytoplasm
What is MCADD?
- medium chain acyl-coenzyme A dehydrogenase
- autosomal recessive
- adhere to a high carbohydrate diet, or use iv glucose so that body not dependent on fatty acids for energy
