Lipid synthesis Flashcards
Synthesis of palmitate:
Has 16 carbons. Primary FA that we make; no DB’s, fully saturated.
Where does most fatty acid synthesis take place
liver;
What does excess acetylCoA convert to?
Fatty acid esters which are our triglycerides. This occurs in the CYTOPLASM
What does fatty acid synthesis require
- ATP
- NADPH
- acetlCoA carboxylase; our rate limiting step
- Fatty acid synthase (large multisubunit complex)
Where do we get NADPH for FA synthesis
- PPP pathway
2. malic enzyme –>converts malate directly to pyruvate and in so doing makes NADPH
What is the first step of palmitate synthesis
Synthesis of MalonylCoA; acetylCoA with CO2 stuck on end. Biotin associated attached with lysine. This makes malonylCoA. The synthesis of malonylCoA requires acetylCoA carboxylase, biotin and ATP
What is step 2
- Malonyl CoA binds to acyl carrier protein
2. Acetyl group from acetyl CoA attaches to KS.
What are the 4 steps of elongation
- Condensation: acetyl group transferred to malonyl group on ACP; CO2 is released
- Reduction: NADPH is used to reduce aldehyde to alcohol
- Dehydration: water is removed to form DB
- Reduction: NADPH is used to reduce DB
What does malonyl acetyl transferase do
Takes 4 carbon unit from ACP and transfers it to KS; leaves ACP empty for new malonyl CoA to come in.
Which enzyme is responsible for condensation
KS
Which enzyme is responsible for reduction
KR
Which enzyme is responsible for dehydration
DH
Which enzyme is responsible for second reduction
ER
What is being produced in the first round of palmitate synthesis
4C acyl chain
- Then 6 more rounds that each add 2 C to make a total of 16
- Total of 7 rounds
What is overall being produced
7 malonylCoA
7 ATP
14 NADPH
Where does the conversion of palmitate to other FA’s occur
smooth ER
What does elongation require in order to convert palmitate to other FA’s
- palmitoylCoA with no ACP and malonylCoA
- NADPH
- stearic acid
how many carbons in stearic fatty acid
18- no double bonds
what does desaturation require (prod DB)
oxygen, NADH and cytochrome b5, DB usually occurs at number 9 position
What is the rate limiting step
adding acetylCoA carboxylase
Most of acetyl CoA we make is in:
mitochondria; no mitochondrial transporters; so you have to convert them to citrate to make it go to cytoplasm for FA synthesis
How is citrate formed
oxaloacetate + acetyl CoA; citrate lyase converts it back to ^
What activates citrate lyase
insulin; its our fed hormone and we want to store energy as fat; so we convert it to tryglycerides and send it to adipose
Glucagon and ___inhibit process
epinephrine
How do you make glycerol - 3-phosphate
- In liver, glycerol is taken up and adds ATP via glycerol kinase–>glycerol3phosphate
- In adipose: goes through dihydroxyacetone phosphate and needs NADH to make glycerol-3-phosphate
what is precursor of triglycerides
glycerol 3 phosphate
Synthesis of triglycerides:
Triacylglycerol and Phosphatidic Acid
- Long chain fatty acylCoA’s are substrates to add FA’s at carbon 1 and 2 via acyl-CoA synthetase. This requires ATP
- Phosphatidic acid phosphatase removes phosphate; acyl transferase adds 3rd FA to form triacyglcerol; addition of each FA requires 2 high energy bonds
what are the broken down steps to make triacylglycerols
- glucose + aa –> acetyl coA via activation of insulin to activate glycolysis
- Acetyl cOA converts to malonyl CoA makes fatty acids
- Fatty acids make triacylglycerols
What is lipoprotein lipase
activated by insulin; binds to lipoproteins and cleaves off lipids from triglyceride and releases glycerol back in to bloodstream which goes back to liver which can be made into glycerol 3 phosphate to make more triglycerides. Free FA come into adipose to combine with triacylcerols for storage
What are the different things that can be attached to polar head group of phospholipids
- Serine
- Ethanolamine
- Choline
- Glycerol
- Inositol
- cardiolipid
What are two strategies to attach head groups
- Diacylglycerol activated with CDP and then stick on glycerol, inositol, or cardiolipin
- Head group activated with CDP; ethanolamine or choline
Phosphatidylserine is made via ___exchange
base; with PE or PC
Phosphatidylcholine is made from
PE; which is made from CDP choline +DAG or methylation of PE
Phosphatdilethalamine is made from
CDP-ethanolamine +DAG
Sphingolipids have ___backbone
serine
PalmitoylCoA + serine=
sphingosine + CO2
Sphingosine + acetylCoA =
ceramide + CoA
Ceramide + PC=
sphingomyelin +DAG
Ceramide + UDP-glucose =
cerebroside +UDP
multiple sugars =
globoside; blood group antigens
Sphingosine are:
Serine backbone with palmitoyl CoA
Ceramide can convert to cerebroside or ____
sphingomyelin
What are four major stages of cholesterol synthesis
- Condensation:3 Acetyl CoA to make mevalonate + CoA
- Formation of activated isoprene: via mevalonate +3 ATP
- Polymerization: squalene + 6 CO2
- cyclization &transformation: end up with cholesterol
What makes ketone bodies
HMG CoA lyase
What is the committed step in cholesterol synthesis
HMG CoA reductase; activated by insulin, and blocked by glucagon.
What is found in fungal pathogens
Engosterol
Cholesterol head groups get masked so it becomes ____so it could get stored. They do this by forming ____
hyrophobic; esters
What does ACAT do
Enzyme to make cholesterol esters from cholesterol.
Prostaglandins and thromboxanes are made from an enzyme called:
prostaglandin endoperoxide synthase (COX)
What are the two catalytic activities of prostaglandin enderoperoxide synthase
- cyclooxygenase
2. peroxidase
What are the end products of eicosinoids
- Prostaglandins
- Thromboxane
- Leukotriene
What inhibits phospholipase A2
Cortisol
WHat is Cox1
Made all the time in most cells. Required for gastric tissue, renal homeostatsis, and platelet aggregation
What is Cox 2
Inducible in response to inflammation; PGs mediate pain, heat, redness, swelling of inflammation.
What inhibits both Cox1 and Cox2
Aspirin and indomethacin
What do Cox2 inhibitors cause
clots; production of thromboxane A2, and loss of production of PGI2
There are ___lipoxygenase inhibitors and leukotriene receptor antagonists are used to treat
5; asthma
what makes leukotrienes
lipoxygenase
