Lipids Biosynthesis (mini-test 1 AND 2) Flashcards
Lipids are made from just 2 precursor molecules. What are they?
1) FAs
2) isoprene
Where are lipids located?
-cytoplasm of liver
-adipose tissue
-kidney
-brain
-breast
-muscle
What materials are needed to make fats?
-acetyl CoA which will be converted to malonyl CoA with acetyl CoA carboxylase
-ATP
-NADPH
-CO2
-vitamin B7/biotin
Where is acetyl CoA made?
in mitochondria
Where is malonyl CoA made?
in cytoplasm
What is step 1a of lipid biosynthesis?
-citrate shuttle is used for exporting acetyl CoA from mitochondria to cytoplasm
-this generates NADPH with malic enzyme
What are the 2 major sources of NADPH?
1) malic enzyme from citrate shuttle
2) PPP
What is step 1b of lipid biosynthesis?
test q
-acetyl CoA is the major substrate to build up FAs
-acetyl CoA, ATP, CO2, biotin/vitamin B7, and acetyl CoA carboxylase undergo a reaction to make malonyl CoA and ADP
-this is the rate limiting step of FA biosynthesis
What is the most important enzyme of biochem 2?
acetyl CoA carboxylase
Which enzyme converts acetyl CoA to malonyl CoA?
acetyl CoA carboxylase
What 3 carboxylase enzymes have we talked about that all require ABC?
1) pyruvate carboxylase (RLE in gluconeogenesis, converts pyruvate to OAA)
2) propionyl CoA carboxylase (converts propionyl CoA to MMCoA)
3) acetyl CoA carboxylase (converts acetyl CoA to malonyl CoA)
3 enzymes require biotin: pyruvate carboxylase, propionyl CoA carboxylase, and acetyl CoA carboxylase. So when theres a biotin deficiency, what happens?
-accumulates pyruvate, propionyl CoA, and acetyl CoA
-eventually will cause acidosis bc they’re all acidic
-causes gray mucus
-long term will cause peripheral neuropathy, hair loss, and pale skin
Which step of FA biosynthesis is reverse steps of beta oxidation?
step 2 of FA biosynthesis
What is step 2 of FA biosynthesis?
-repetitive steps catalyzed by FA synthase (also known as fatty acyl synthase)
-an enzyme complex is used with 7+ catalytic activities
In beta oxidation, you break from the __________ end, but in FA synthesis, you build from the _________ end
carboxyl, methyl or omega
What is step 3 of FA biosynthesis?
-priming of fatty acyl synthase/acyl synthase
-2 carbons from the acetyl CoA is transferred to the KAAS site to charge the enzyme
-the first 2 carbons added are derived from acetyl CoA and become the last 2 carbons of the complete FA
-only the acid will be linked to the synthase
-fatty acyl chain will elongate and this will undergo 4 reactions
What is step 3A of FA biosynthesis?
condensation rxn
-malonyl CoA is transferred to the ACP binding site
-malonyl CoA condenses with acetyl chain on KAAS, liberating carbon dioxide
-the elongating acyl chain moves back to ACP and creates ketoacyl-ACP and will release CO2
What is step 3B of FA biosynthesis?
reduction rxn
-ketoacyl-ACP is reduced by ketoacyl-ACP reductase using NADPH to generate beta hydroxyacyl-ACP
What is step 3C of FA biosynthesis?
dehydration rxn
-hydroxyacyl-ACP dehydratase removes water from the beta and alpha carbon to create a double bond between them in enoyl-ACP
What is step 3D of FA biosynthesis?
reduction rxn
-enoyl-ACP reductase reduces the double bond to create a saturated fatty acyl chain using NADPH
-the fatty acyl now is longer by 2 carbons and is transferred back to KAAS site
-the next malonyl CoA is bound at the now vacant ACP site so the process can be repeated
-the cycle will continue until the fatty acyl chain is 16 carbons long (palmitate), anything longer requires a seperate elongation system
How many malonyl CoA and acetyl CoAs are needed to synthesis palmitate?
7 malonyl CoA (for elongation) and 1 acetyl CoA (for initial charging of FA synthase)
What 3 enzymes create NADPH?
1) G6P DH
2) 6 phosphogluconate DH
3) malic enzyme
What is the most common product of fatty acyl synthase?
palmitate 16:0
How many NADPHs are used to make palmitate?
14 NADPH (2 per cycle, so 7 cycles used 14)
What does malonyl CoA require to be synthesized?
-acetyl CoA
-ATP
-biotin
-CO2
CO2 is a byproduct of which reaction in FA biosynthesis?
condensation rxn (step 3A)
Where does FA synthesis occur?
in cytoplasm
Where does beta oxidation occur?
in mitochondria
Is FA biosynthesis exergonic or endergonic?
endergonic (stores energy)
Is beta oxidation exergonic or endergonic?
exergonic (creates energy)
What is the difference between FA biosynthesis and beta oxidation in terms of electron carriers?
FA biosynthesis requires NADPH, whereas beta oxidation generates NADH
What is the difference in carbons between FA biosynthesis and beta oxidation?
FA biosynthesis= the FA chain is built in a cylindrical rxn sequence that adds 2 carbons to the chain per turn, however, the primary building block is not the 2 carbon acetyl CoA but the 3 carbon malonyl CoA. The extra carbon of malonyl CoA is derived from CO2
beta oxidation generates a 2 carbon product
What coenzymes are required for beta oxidation?
FAD, NAD+, and CoA
What are the 4 steps of FA biosynthesis elongation?
1) condensation
2) reduction/ dehydrogenation
3) dehydration
4) reduction/ dehydrogenation
Fatty acyl synthase can only make acyl chains 12-16 carbons longs. However, many of the critical FAs in the cell are longer than this. Palmitate is elongated using a different set of enzymes but in much of the same way as fatty acyl synthase in cytoplasm. This process is catalyzed by the fatty acyl elongation system, which is found in the….
SER and mitochondria
Many FAs in the cell are unsaturated (contain cis double bonds/ Saturated FAs such as palmitate 16:0 and stearate 18:0 are desaturated by ____________________ which is found in the SER
fatty acyl desaturase
In humans, fatty acyl desaturase cannot place double bonds beyond carbon ____. Consequently, any FA with a double bond beyond this will be essential/ required in the diet
9
What are the 2 essential FAs?
1) linoleate 18:2 delta 9, 12 (omega 6)
2) alpha linolenate 18:3 delta 9, 12, and 15 (omega 3)
How do you calculate omega?
take total number of carbons and subtract last double bond number and it should be either omega 3,6, or 9
note: only omega 3 can synthesize 3, 6 can synthesize 6, 9 can synthesize 9
What is the most important regulatory step of FA biosynthesis?
malonyl CoA synthesis
acetyl CoA undergoes reaction with ATP, CO2, biotin, and acetyl CoA carboxylase to make malonyl CoA and ADP
What are the activators of acetyl CoA carboxylase?
-high insulin
-high ATP
-high citrate or isocitrate
-high acetyl CoA in cytoplasm
What are the inhibitors of acetyl CoA carboxylase?
-high glucagon
-high ADP
-high palmitoyl CoA (same thing as palmitate)
Both TGs and glycerophospholipids are made from….
1) glycerol 3 P
2) acyl CoA
How is glycerol 3 phosphate generated?
2 different ways:
Glycerol 3 phosphate binds 2 FAs and changes to ______________________, which is the branch point for synthesizing TGs or glycerophospholipids. Option 1 is a fatty acid replaces the phosphate in carbon 3 and creates TGs. Option 2 is a head group like choline will directly attach and create phospholipids
phosphatic acid (simplest phospholipid and most abundant)
Which hormone does this?
-increases glycolysis
-deceases gluconeogenesis
-increases in FA synthesis
-decreases in FA mobilization and beta oxidation (FA breakdown)
insulin
Which hormone does this?
-decreases in glycolysis
-increases in gluconeogenesis
-decreases in FA synthesis
-increases in FA mobilization and beta oxidation (FA breakdown)
-increases ketogenesis (liver) and ketolysis
glucagon
Cholesterol and other related steroids are members of the ____________ family
isoprene
Cholesterol biosynthesis occurs in the…..
cytoplasm of liver cells
All the carbons of cholesterol are derived from….
acetyl CoA
Acetyl CoA can change to cholesterol or….
FAs
What is the difference between ketone body synthesis and cholesterol synthesis?
location
cholesterol is synthesized in cytoplasm of liver cells
ketone bodies are synthesized in mitochondria of liver cells
What is step 1 of cholesterol synthesis?
-2 acetyl coA undergo a reaction and make acetoacetyl CoA and releases a CoA
-acetoacetyl CoA then undergoes a reaction with another acetyl CoA to make HMG-CoA and release another CoA
-HMG CoA (6C) then undergoes a reaction with HMG-CoA reductase (RLE) to make mevalonate (6C)
What is the RLE of cholesterol synthesis?
HMG-CoA reductase
Statin drugs are a competitive inhibitor and compete with the active site with what enzyme?
HMG-CoA reductase (so if statin does bind to active site then no cholesterol will be made)
What is the precursor for isoprene and is the product of the RLE in cholesterol synthesis?
mevalonate
What is step 2 of cholesterol synthesis?
formation of activated isoprene (now is 5C)
What is step 3 of cholesterol synthesis?
formation of squalene (now is 30C)
-6 isoprenes bind together to make 1 squalene
-use NADPH and oxygen to close the ring structure of cholesterol
What is step 4 of cholesterol synthesis?
cholesterol formation, now is 27 carbons
What steroid hormones can be made from cholesterol?
-glucocorticoids like cortisol
-mineralocorticoids like aldosterone
-sex hormones like androgen, estrogen, and progesterone
80% of cholesterol becomes….
bile acid salts and most of it will be recycled/reabsorbed
What is the active form of HMG CoA reductase?
without phosphate
What are the inhibitors of HMG CoA reductase?
-high glucagon
-high cholesterol
What are the activators of HMG CoA reductase?
-high insulin
-high T4/ thyroxine (also activates bile acid)
T/F: cholesterol synthesized in body has a higher affect on blood cholesterol levels than the diet
TRUE
What is the best food to eat if you have high cholesterol levels?
plant based foods because theres no cholesterol, low saturated FAs and theres lots of fiber
in terms of animal foods
-could eat 1 egg or salmon
What is the product of HMG CoA reductase?
mevalonate
What has the most influence on raising total blood cholesterol levels?
saturated FAs
