Lecture 13 - Lipid Synthesis Flashcards
What breaks down triglycerides to fatty acids?
Lipases
What breaks down fatty acids to acetyl CoA?
Beta-oxidation
What breaks down acetyl CoA to CO2?
TCA cycle
____ are more efficient energy storage than ______
- Fatty acids
- Carbohydrates
What is the precursor of fatty acid biosynthesis?
Acetate
Do beta-oxidation and fatty acid synthesis use the same enzymes?
Nope
Where does fatty acid synthesis occur?
Cytoplasm
Where does beta-oxidation occur?
Mitochondria
What is required as an activator for fatty acid synthesis?
Citrate
What is required but not incorporated in fatty acid synthesis?
CO2
What is the principle enzyme of fatty acid synthesis?
Fatty acid synthase
What is fatty acid synthase like in eukaryotes?
One large protein, with several activities
What is fatty acid synthase like in prokaryotes?
Complex of several proteins, each with a different activity
What occurs in the preparatory phase of fatty acid synthesis?
Acetyl CoA is converted to malonyl CoA
What enzyme is used in the preparatory phase of fatty acid synthesis?
Acetyl CoA carboxylase
What cofactor is needed in the preparatory phase of fatty acid synthesis?
- CO2 in
- ATP -> ADP + Pi
- Biotin
Which step is the rate limiting step of fatty acid synthesis?
The preparatory phase/step
What controls the slowest step of fatty acid synthesis and what is it needed for?
- Citrate
- Required for oligomerization of the enzyme
Why is biotin needed for the preparatory phase of fatty acid synthesis?
CO2 carrier
What are the 2 activities that occur in acetyl CoA carboxylase and what does each do?
1) Biotin carboxylase - attaches CO2 to biotin
2) Transcarboxylase - transfers CO2 from biotin to acetyl CoA, making malonyl CoA
What is the active portion of the acyl-carrier protein and what does it form?
-SH forms thiol esters with fatty acid molecules
What type of chain does acyl-carrier protein have?
4-phosphopantetheine chain
What does the 4-phosphopantetheine chain do?
“Carries” the growing fatty acid chain from enzyme to enzyme (bacteria) or active site to active site (eukaryotes)
What are the 2 sources of NADPH?
1) From pentose phosphate pathway in liver cells
2) From malic enzyme in fat cells
What are the sources of acetyl CoA?
Ethanol, pyruvate, amino acids, acetate, and citrate
What enzyme and cofactor are needed to generate acetyl CoA from citrate?
- ATP-citrate lyase
- ATP -> ADP + Pi
Where does production of acetyl CoA from citrate occur?
Cytoplasm
Where does production of citrate from acetyl CoA and oxaloacetate occur?
Mitochondria
What happens to excess acetyl CoA in the mitochondria?
- Converted to citrate in mitochondria
- Transported to cytoplasm
- Shunted to fatty acid synthesis
- Excess oxaloacetate is converted to malate, and then pyruvate can go back into mitochondria to pick up more acetyl CoA
At which carbons can unsaturations be introduced?
C4, C5, C6, and C9
What enzyme and cofactor are needed to introduce an unsaturation?
- Fatty acyl-CoA monoxygenase
- O2 -> 2 H2O and NADH + H+ -> NAD+
How is fatty acid synthesis controlled?
1) Enzyme activity
2) Transcription
3) Hormones
What is the central role of citrate?
To control energy metabolism
What does citrate activate?
Gluconeogenesis, for energy storage
What does citrate inhibit?
Energy release
What does citrate act as during energy rich conditions?
A source of acetyl CoA for additional lipid synthesis
What does protein kinase activate?
Pancreatic lipases and beta-oxidation
What does protein kinase inactivate?
Lipid synthesis
What does insulin activate during high glucose conditions?
Acetyl CoA synthesis, as a means of storing energy in the form of fat
Energy poor conditions induce transfer of metabolites to _______ for _____
- Mitochondria
- Energy production
Energy rich conditions induce transfer of metabolites to ______ for
- Cytoplasm
- Fatty acid synthesis (energy storage)
Are fatty acids normally found as free entities?
Nope
How do fatty acids primarily exist?
In complex lipids
What are the precursors for steroid hormones?
Cholesterol
Are cholesterol, phospholipids, and triacylglycerols soluble or insoluble and what does this mean?
- Insoluble
- Must be transported by protein carriers in blood
What are the 4 types of lipoproteins?
1) HDL
2) LDL
3) VLDL
4) Chylomicrons
Which type of lipoprotein has the highest amount of cholesterol?
Chylomicrons
What is the function of HDL’s?
Return cholesterol to the liver
Which type of lipoprotein is the least dense?
Chylomicrons
What is the function of chylomicrons?
Transport fatty acids to various tissues for fuel or storage
Which lipoproteins have receptor mediated uptake?
Chylomicrons, VLDL, and LDL
Where are VLDL’s made?
In liver when there is excess fatty acids
What is the function of VLDL?
Transport triacylglycerols and cholesterol to muscle and adipose tissue
What does a VLDL have to lose to become a LDL?
Triacylglycerol
What is the function of LDL?
Transport cholesterol to hepatic tissues
Which lipoprotein contains the highest amount of protein?
HDL
What does HDL have that the other lipoproteins don’t and what does it do?
Has acyl transferases on surface to convert cholesterol to cholesterol esters
What does a high LDL/HDL ratio indicate?
A need to reduce fat intake
What does familial hypercholesterolemia lead to and why?
- Increased LDL in blood -> plaque formation -> atherosclerosis
- Express fewer LDL receptors
Why is HDL considered “good cholesterol”?
Has acyl transferases which convert cholesterol to cholesterol esters, which transport cholesterol back to the liver for bile salts
How can cholesterol biosynthesis be controlled?
Inhibition of HMG-CoA reductase
What do resins do to bile acids?
Bind bile acids and remove them from metabolism, therefore causing more cholesterol to be converted to bile acids
How can red wine decrease cholesterol?
Increases LDL receptor expression, suppresses secretion of apolipoproteins, and protects against oxidation of LDL
