Lipid Metabolism Flashcards
What are lipids?
- group of molecules that are insoluble in water
What is the principle functions of lipids in the body?
- stored energy
What structural aspect in the body do lipids primarily contribute towards?
- biological membranes
How do lipids help with digestion in the GIT?
- act as an emulsifying agent
Do lipids that are stored as energy have positive or negative charge?
- neutral charge
Do membrane bound lipids contain a positive or negative charge?
- both - hydrophobic and hydrophilic
- negative in middle, positive on outside
What is the basic structure of a glycerophospholipids?
- glycerol backbone
- 2 fatty acids
- 1 phosphate attached to alcohol group
What is the basic structure of a sphingolipids?
- glycerol backbone
- 1 fatty acids
- 1 mono or oligosaccharide
What is the basic structure of a galactolipids?
- glycerol backbone
- 2 fatty acids
- 1 mono or oligosaccharide attached to a sulphate group
If a lipid is saturated what does this mean when thinking about the carbons?
- carbons have full compliment of H+
Are saturated or unsaturated lipids provide more flexibility to membranes?
- unsaturated
- due to kind in their tails
Unsaturated lipids have a double bond between 2 carbon molecules, what does this mean for the structure of the carbons?
- gives the tail of the lipids a kink
- makes the membrane it is part of more flexible
Are saturated and unsaturated more likely to be solutions or solids?
- saturated = solid and a ⬆️ melting point (butter)
- unsaturated = liquid and a ⬇️ melting point (olive oil)
What are the 2 major pathways of triglyceride metabolism?
- B oxidation = releaseing energy
- Synthesis = S for storing energy
Why is B oxidation called B oxidation?
- removal of electrons
- occurs prior to beta carbon
What is the first step of B oxidation?
- fatty acids are activated by coenzyme A
- coenzyme A attaches to fatty acid
In the mitochondria where do fatty acids become activated by the coenzyme A attaching to it?
- cytosol
What is an acyl group?
- carbon attached to O with double bond
- R tail is the fatty acid
What is the carnitine shuttle?
- exchange between CoA and carnitine groups
- facilitates acyl groups from cytosol to matrix of mitochondria
How does the carnitine shuttle move acyl across the inner mitochondrial membrane?
- acyl-CoA is converted into acyl-carnitine
- enzyme carnitine palmitoyl 1 cleaves CoA from fatty acid
- leaving Carnatine attached to fatty acid
- THIS IS THE RATE LIMITING STEP OF CARNATINE SHUTTLE
Once inside the matrix how does the carnitine shuttle keep acyl groups inside the matrix?
- acyl-carnitine is converted back into acyl-CoA
- enzyme carnitine palmitoyl 2 cleaves carnatine from fatty acid
- leaving CoA attached to fatty acid
What is the carnitine palmitoyl transferase I?
- enzyme
- converts acyl-CoA into acyl-carnitine
What is the carnitine palmitoyl transferase II?
- enzyme
- converts acyl-carnitine into acyl-CoA
What is the rate limiting step in B oxidation?
- carnitine shuttle
- exchange of acyl-CoA to acyl-carnatine
What is step 3 of B oxidation?
- multiple oxidation steps
- 2 carbon units removed each time
- 1 FADH2 and 1 NADH are formed per cycle
During each B oxidation cycle how many acetyl-CoA, FADH1 and NADH are formed?
- acetyl-CoA = 1 can then enter the cirtic acid cycle
- FADH1 = 1 = 1 can then enter the TCA
- NADH = 1 = 1 can then enter the TCA
Once the 2 carbon units have been oxidised from long fatty acid chains what cycle does it enter within the matrix of the mitochondria?
- Kreb Cycle also know as the citric acid cycle
If there are mutations in the enzymes responsible for B oxidation, what can this cause in infants (SIDS)?
- sudden infant death syndrome
- cannot use lipids as energy
If a fatty acid has a long tail, how do you calculate how many cycles of B oxidation it needs to go through?
- total number of carbons in tail divide by 2
- then subtract 1
What does a hydrase enzyme do to a molecule?
- adds H2O to a molecule
- like hydrating it
What is dehydrase enzyme?
- removes H+
- like dehydrating it
What is fatty acid synthesis?
- fatty acids are stored as adipose tissue
What are the 2 primary sites where fatty acid synthesis takes place?
- liver
- adipose tissue
Where does fatty acid synthesis take place?
- cytosol of mitochondria
In order for fatty acid synthesis to occur acetyl CoA is needed, but it is within the matrix of the mitochondria. How is acetyl CoA removed from the mitochondrial matrix to facilitate fatty acid syntheis?
- oxaloacetate (OAA) and acetyl-CoA (AcCoA) are converted into citrate
- the enzyme citrate synthase facilitates this
Once inside the cytosol what is required to breakdown citrate?
- energy from ATP
- phosphate group removed from ATP becoming ADP
What is the enzyme that converts citrate into acetyl-CoA and oxalvacetate from citrate?
- citrate lyase
Once oxalvacetate has been formed in the cytosol from citrate, how does it get back into the matrix?
- oxalvacetate converted to malate
- malate converted to pyruvate and re-enters matrix
What is Malonyl-CoA?
- coenzyme that inhibits fatty acids entering mitochondria
What does Acetly-CoA carboxylase do to Acetly-CoA?
- adds a CO2 to Acetly-CoA = 3 carbon molecule
- this new molecule is called Malonyl-CoA
What happens if there is too much citrate in the cells?
- citrate is moved out of the mitochondria
- citrate activates Acetly-CoA carboxylase
- Acetly-CoA carboxylase increases fatty acid synthesis
What is the largest molecule that can be made from fatty acid synthesis?
- 16 carbon molecule
What is the rate limiting step of fatty acid synthesis?
- formation of Malonyl-CoA
If the body recognised that there is a lot of fatty acids being stored through fatty acid synthesis, what enzyme can be inhibited to stop this process?
- Acetly-CoA carboxylase
- phosphorylates the enzyme
What are a 2 hormones that can initiate the phosphorylation and inhibition of Acetly-CoA carboxylase?
- Acetly-CoA carboxylase = synthesis lipogenesis
- glucagon
- adrenaline
Does cholesterol need to be consumed?
- no
- all cells can synthesis it
What does an amphipathic molecule mean?
- posses both hydrophobic and hydrophilic properties
How is cholesterol synthesised and eliminated from the body?
- acetyl-CoA - eliminated through bile acids
What form is cholesterol generally stored as?
- cholesterol ester
What enzyme is required to esterify cholesterol into cholesterol ester?
- acyl-CoA Cholesterol Acyltransferase (ACAT)
What does cholesterol contribute to the formation of in the liver before it is secreted into the GIT?
- bile acids
Are bile acids hydrophobic or hydrophillic?
- predominantly hydrophillic
What do biles acids act as in the GIT to help fat digestion?
- emulsifiers
What is the main role of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA)?
- precursor for mevalonate
- mevalonate pathway
- responsible for cholesterol production
What is the first step of cholesterol synthesis?
- synthesis of mevalonate from acetate
- acetate converted into HMG-CoA
- HMG-CoA converted into Mevalonate
What is the second step of cholesterol synthesis?
- conversion of mevalonate to isoprenes
What is the third step of cholesterol synthesis?
- condensation of 6 isoprene to squalene
What is the fourth step of cholesterol synthesis?
- cyclisation of squalene to steroid nucleus
What is the rate limiting step, and also the target for the statins in cholesterol synthesis?
- conversion of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) to mevalonate
- inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA)
Short chain fatty acids are the exception to other lipids and are transported in the blood on a specific protein, what is this protein?
- albumin
The majority of lipids (not short chain fatty acids) are transported around the body using special carrier proteins called what?
- lipoproteins
What are the 3 characteristics that lipoproteins have that allow them to move freely?
- hydrophobic
- hydrophilic
- amphipathic
What are apoproteins?
- carrier proteins
- combine with lipids to form classes of plasma lipoproteins
What is the largest class of lipoproteins?
- chylomicrons
What are 2 important classes of apoproteins attached to chylomicrons?
- ApoE and ApoC-II
What is the order of size of HDL, LDL, IDL, VLDL and chylomicrons?
- smallest to largest
- HDL, LDL, IDL, VLDL and chylomicrons
What makes a lipoprotein bad?
- the amount of cholesterol - LDL has largest amount 35-40%
What has to happen to lipids in the GIT for them to be broken down?
- bile released from gall bladder to emulsify lipids
- enzymes released to hydrolyse lipids
Once absorbed what system do chylomicrons enter first?
- lymphatic system
- then into the blood
What is exogenous, meaning the lipids come from outside of the liver, pathway for lipid transport?
- lipids consumed through dietary intake
- digested, packaged into chylomicrons and into lymphatics
- enter circulation at internal jugular vein
- then transported around the body
What apoprotein can be found on chylomicrons that can initiate the release of capillary lipase to digest fatty acids for energy?
- ApoC-II
During exogenous transport of lipids what happens to any chylomicrons that have not been absorbed?
- enter the liver to be processed into VLDL
Once processed in the liver lipids are then transported to the body, is this exogenous of endogenous?
- endogenous
What is the main transport lipoprotein that the liver used to transport lipids?
- very low density lipoproteins (VLDL)
Any VLDL that lose more TAGs whilst being transported around the body become what lipoprotein?
- intermediate lipoprotein
If intermediate lipoproteins continue to lose TAGs what can happen to them?
- re-enter the liver for storage
- processed into low density lipoproteins (LDL) and stored as fat
In LDL lipoproteins what apoprotein initiates the storage of LDL as adipose or visceral fat?
- ApoB-100
Which lipoprotein is seen as the reversal of lipid/cholesterol stroage, because it collects lipids and cholesterol from the peripheries?
- HDL picks up endogenous cholesterol
- HDL then returns it to the liver
Endogenous cholesterol in HDL is then absorbed by cells in the liver, not through endocytosis, but by what scavenger receptor?
- B1 (SR-B1)
LDL can be stored in adipose and visceral adipose tissue through ApoB-100. How does LDL enter cells?
- ApoB-100 binds to LDL receptors on cells
- undergoes endocytosis
- digested and stored as fat
- receptors are recycled and returned to cell surface
How are cellular cholesterol levels controlled?
- regulating LDL uptake
- regulating LDL biosynthesis
What is the short term regulator and the rate limiting step for cholesterol levels?
- HMG-CoA reductase activity
- converts HMG-CoA to mevalonate
- statin target
What are the long term regulators for cholesterol levels?
- regulation of transcription, protein production and protein degradation
- down regulation of HMG-CoA reductase activity
- down regulation of LDL receptors
What is the function of Apolipoprotein C II (ApoC-II)?
- protein in plasma
- activates capillaries to release lipoprotein lipase
- absorbs lipids of lipoproteins
What are glycolipids?
- lipids attached to carbohydrates
- form antigens on cell surfaces
What is the function of Apolipoprotein B 100 (ApoB-100)?
- protein on lipoprotein
- binds with adipose to phagocytose cholesterol and lipids
- stored in cells as fat
Apolipoprotein C II (ApoC-II) signals blood capillaries to release lipoprotein lipase. Which lipoproteins can ApoC-II be found on?
- chylomicrons
- VLDL
What is the function of Apolipoprotein E (ApoC-E)?
- protein in plasma
- liver recognised ApoC-E and engulfs lipoproteins using endocytosis
- thin E for End of the road for lipoproteins
Why does the body convert cholesterol into cholesterol esters?
- ensures packaging in centre of lipoproteins
- means lots of cholesterol can be packaged
- reduces cholesterol in blood
