Roesler section post midterm Flashcards
what are the four classes of lipids?
Fatty acids
triacylglycerols
phospholipids
cholesterol
How are fatty acids numbered? what are carbons 2 and 3 in the chain?
Usually numbered beginning with carboxyl terminal carbon atom
- 2 and 3 are a and b respectively
Why can we get so much energy out of fatty acids?
because it exists in a highly reduced state
What is the storage form of fatty acids?
triacylglycerol
Can the liver synthesize fats from carbs?
yes
How many ATP can you get from 1 fatty acid?
about 100
are fatty acids hydrophilic or hydrophobic?
both : amphipathic
How do we absorb dietary triacylglycerols?
- too hydrophobic to cross biological membranes
- degraded in small intestine and resynthesized in intestinal cells via enterocytes
What does an omega 3 refer to?
placement of the first double bond on carbon three starting from the omega (CH3 end)
What kind of tissue are triacylglycerols stored in?
Adipose tissue
Do saturated fatty acids have double bonds?
no
What do lipases do?
break down lipids and usually release a fatty acid
What is the result when pancreatic lipase breaks down a triacylglycerol?
- cannot release all 3 FA
- middle FA is inaccessible to active site
- TG turns into a monoacylglycerol and 2 FA
What are chylomicrons?
type of lipoprotein
- fat shuttle
- synthesized only in intestine and released into circulation
-allow for transport of insoluble lipid (TGs) into blood stream to tissues - mainly muscle
-triacylglycerol makes up the core
How much energy can we get out of TG?
37 kJ/g or 9kCal/g
What form are TGs stored as?
anhydrous - means theres no water - way less weight than glycogen
What are two roles for protein components of plasma lipoproteins?
- solubilize hydrophobic lipids
- contains cell targeting signals
What are the 5 classes of lipoproteins? What is the distinguishing factors?
Chylomicron
VLDL
IDL
LDL
HDL
- different proportions of TG and cholesterol attached
- diff protein components
- made in liver - IDLs are VLDL remnants used to make LDLs
What are the two products when TGs are broken down?
fatty acid plus glycerol
What can glycerol made from lipolysis be used in?
gluconeogenesis
Where does fatty acid oxidation occur?
in the mitochondrial matrix
What two things need to happen to oxidize fatty acids?
- needs to be activated - bound to CoA
- needs to be transported, carnitine shuttle
What is the rate limiting step pf fatty acid oxidation?
fatty acid transport into the mitochondria
- carnitine shuttle has low activity at energy surplus
- high activity when energy deficient
- 1st step of the carnitine shuttle is regulated
What are the three steps in ATP production from fatty acids?
B oxidation - degradation of fatty acids (acyl CoA), 2 carbons at a time producing Acetyl CoA, NADH, FADH2
2. Acetyl CoA from Boxidation are oxidized to CO2 (TCA)
3. production of ATP
What type of reactions does B oxidation work on?
simple fatty acids
- saturated, no double bonds
- even number of carbons
What is step 1 in B oxidation?
Acyl CoA dehydrogenase oxidizes Acyl CoA to produced a trans double bond between C2 and C3 (making trans enoyl CoA)
What is step 2 in B oxidation?
Hydration of trans Enoyl CoA to L 3 Hydroxyacyl CoA - hydrates and removes double bond
What is step 3 in B oxidation?
Oxidation of L3 hydroxyacyl CoA via Hydroxyacyl CoA dehydrogenase to make 3 ketoacyl coa
What is step 4 in B oxidation?
Thiolase creates an acetyl CoA and an Acyl Coa with carbons 1 and 2 of a fatty acid becoming each acetyl Coa - acyl molecule is one molecule shorter
How many acetyl CoA are made for every two carbons removed from fatty acid?
1 acetyl co a
How do we deal with unsaturated fatty acids?
Enoyl CoA isomerase - moves the double bond from C 3-4 to C 2-3 and changes double bond from cis to trans - B oxidation continues as normal
How do we deal with odd chain fatty acids?
- dont produce them but are in plants so its in our diets
- we have enzymes to deal with it
- early steps are dealt with by beta oxidation until 5 carbons left
- get propionyl CoA - 3 carbons
- above is carboxylated- converted to succinyl CoA - into TCA cycle
Where does B oxidation occur?
mitochondrial matrix
What are Ketone bodies
alternative to glucose as fuel or energy for the brain
- formed by ketogenesis
- usually produced at low rate
- only formed in liver
- synthesis rate increases with starvation
Where are ketone bodies formed?
mitochondrial matrix of liver where acetyl coa is produced -
How are ketone bodies produced
- condensation of 3 acetyl coa to form acetoacetate
- acetoacetate is converted to 3 hydroxybutyrate and acetone
What are the three ketone bodies?
acetoacetate
B hydroxybutyrate
acetone (cant be used for fuel)
How are ketone bodies used as fuel?
all converted to acetoacetate - products are 2 acetyl coa - goes into TCA cycle
Do all ketone bodies produce the same amount of energy when oxidized?
No, because we get an NADH from the conversion of 3 hydroxybutyrate to acetoacetate
is fatty acid synthesis the reversal of B oxidation?
no
Where does FAS occur?
cytosol in liver cells, some adipose tissue
How are fatty acids synthesized?
Fatty acid synthase (FAS)
sequential addition of 2 carbon units derived from acetyl CoA
- stops with formation of palmitate (C16)
When will fatty acids be synthesized from citrate?
When TCA cycle is inhibited - high levels of NADH FADH2 ATP - inhibit Aketoglutarate complex - increase citrate concentration
How do we get citrate out of the mitochondria and into the cytosol for fatty acid synthesis?
Citrate shuttle - moves from mito to cytoplasm
- will generate oxaloacetate and acetylcoa via citrate lyase
- oxaloacetate will go to malate and pyruvate to regenerate oxaloacetate for TCA
What two enzymes are unique to citrate shuttle?
citrate lyase and malic enzyme
What are the two sources of NADPH for fatty acid biosynthesis?
malic enzyme acting on malate in the citrate shuttle
PPP - many more NADPH
What is the first AND rate limiting step in FA synthesis?
Acetyl CoA to Malonyl CoA catalyzed by Acetyl CoA carboxylase - via a carboxyl group transfer
- uses ATP - not reversible
What is Malonyl CoA?
Activated donor for adding fatty acid molecules
What is ACP?
Acyl Carrier protein - has phosphopantetheine group that tethers growing fatty acid chain to FA synthase
(same group as CoA)
How does FAS get loaded with substrates (step 2)
Acetyl CoA turns into Bketoacyl synthase - acetyl via acetyl transacylase
- Acetyl CoA gets added to an SH group
- only Acetyl CoA group - every other one is Malonyl CoA
How does malonyl CoA load FAS with substrates in step 3?
Malonyl transacylase turns it into malonyl ACP - joins with the FAS
What is step 4 condensation in fatty acid synthesis?
B ketoacyl synthase (KS)
- loss of CO2 from malonyl ACP
- transfers 2C from acetyl CoA to malonyl ACP
- makes B ketobutryl ACP
- trying to reduce to make fatty chain
What is step 5 reduction in fatty acid synthesis?
Carbonyl group at C3 is reduced - electron donor is NADPH
What is step 6 dehydration in fatty acid synthesis?
B hydroxyacyl dehydratase
- dehydration reaction
- introduces double bind
- trans butenoyl ACP
What is step 7 reduction in fatty acid synthesis?
Enoyl reductase
- double bond is reduced
- electron donor is NADPH
- forms butryl acp - 4C fatty acid
- completes one round of fatty acid synthesis
What is step 8 in fatty acid synthesis?
translocation
- moves 4C back to starting point
- transfer of butyryl group from ACP to KS - catalyzed by acetyl transacylase
- repeats the other steps to add more
How many cycles does it take to make palmitate?
7 cycles
How many NADPH does fatty acid synthesis need to add 2 carbons?
2 so 14 for the whole thing
Can humans synthesize odd chain fatty acids?
NOOOOOOOOO MOTHER FUCKA
Where does elongation of fatty acid chains occur?
ER - 2 carbons are added at a time - from malonyl CoA
What is desaturation in fatty acid synthesis?
the introduction of cis double bonds - catalyzed by desaturase enzymes (ER)
- location of double bond is specific for each desaturase
humans cannot introduce carbons bonds past carbon ___
NINE
Which two desaturases do humans lack?
12 and 15 desaturases - must be consumed in the diet (linoleate)
How is fatty acid synthesis - acetyl CoA carboxylase - regulated?
- AMPK inhibits synthesis - low energy = high AMPK - phosphorylates ACC - inactive
- High energy = high ATP - AMPK inactive - ACC dephosphorylated - active
Allosterically
- citrate inhibits AMPK - ACC active
- insulin inhibits AMPK - ACC active
- epinephrine activates AMPK - ACC inactive
- glucagon activates AMPK - ACC inactive
- palmitate - inhibits end product
Why is citrate wierd abt activating ACC?
its not active when citrate exists as dimers but does work when it is as a polymer or filament and can actually activate ACC
Where is cholesterol synthesized?
liver
Where does cholesterol get its carbons?, how many are there?
acetyl CoA - 27 carbons
What is the purpose of cholesterol?
- structural component of membranes
- precursor of bile salts, steroid hormones, and vitamin D (not B)
What 5 steroid hormones come from cholesterol?
Progesterone, cortisol, estradiol, testosterone, vitamin D
What is the first stage in cholesterol synthesis?
3 acetyl CoA are used to form mevalonate - mevalonate is eventually converted to 3-isopentenyl phosphate, 6 molecules of that are used to form the precursor squalene - so 18 acetyl CoA are needed for this step for each molecule of cholesterol
What does cholesterol do for membranes?
breaks up rigid structure- increases fluidity of membrane
What is the major rate limiting enzyme in cholesterol synthesis?
HMG CoA reductase - its the target of statins which are competitive inhibitors
What happens to excess cholesterol?
converted into bile acids and stored in the gallbladder
Where are the three locations cholesterol can go after synthesis?
- hepatocyte plasma membrane
- bile acids
- exported in LDLs, blood to tissues
is there a degradation pathway for cholesterol?
No, can only turn till bile acids and excreted through feces
How do three kinds of lipoproteins transport cholesterol?
VLDL - moves TG and cholesterol
LDL - transports cholesterol from liver to tissues (most important)
HDL - picks up cholesterol from blood and tissues
What are the three ways cholesterol synthesis is regulated via HMG CoA reductase?
- when cholesterol drops, the transcription of the gene for HMG reductase is stimulated - activates synthesis - transcription slows when cholesterol levels are high - inhibits synthesis
- rate of translation of HMG CoA reductase mRNA is inhibited by mevalonate metabolites
- degradation of HMG ENZYME is stimulated by elevated levels of cellular cholesterol
How is cholesterol uptake into cells regulated by intracellular levels of cholesterol?
LOW cholesterol - will increase HMG, LDL, synthesis and uptake
HIGH cholesterol - will decrease HMG, LDL, synthesis and uptake
this is important for peripheral tissues
What is familial hypercholesterolemia?
high circulating cholesterol levels
- severe atherosclerosis
- defective LDL receptor
- cholesterol is not properly cleared from blood
What are the three most common membrane phospholipids?
Phosphatidylcholine
Phosphatidylethanolamine
Phosphatidylserine
What is the starting substrate for both TG and PL synthesis?
glycerol 3 phosphate (activated form of glycerol)
-glycerol from adipose tissue goes to liver and becomes G3P via glycerol kinase
- glycerol from other tissues comes from glucose and is converted via glycolytic pathways
What is the most abundant phospholipid?
phosphatidylcholine
How is phosphatidylcholine synthesized?
CDP-choline pathway in all tissues
- diacylglycerol and CDP choline make phosphatidylcholine via CDP-choline diacylglycerol phosphocholine transferase
What does acyltranferase do?
catalyzes sequential attachment of fatty acids to glycerol backbones (ester bond)
What is phosphatidate?
important intermediate in both TG and PL synthesis
- loses phosphate group to become diacylglycerol
What is the second pathway for synthesizing phosphatidylcholine?
methylation pathway in the liver
- phosphatidylethanolamine becomes phosphatidylcholine
What phospholipid is a substrate / precursor for phosphatidylserine and phosphatidylcholine?
Phosphatidylethanolamine
How do you make phosphatidylethanolamine?
Phosphatidylserine and PS decarboxylase makes phosphatidylethanolamine and releases a CO2
What are all eicosanoids synthesized from?
arachidonate 20c(?)
What are the major eicosanoids?
leukotrienes
prostaglandin
What releases arachidonate?
Phospholipase A2 - released from phospholipids in the membrane
What type of hormones are eicosanoids and what does that entail?
-paracrine hormines
- not stores but rapidly degraded
-send messages to nearby cells or tissues including the cell in which it was made
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