Lipid Metabolism (mini-test 1 AND 2) Flashcards
What is the major lipid in the body?
triglycerides
What is triglyceride also known as?
-TG
-triacylglycerol
-TAG
-glycerol w/ 3 FAs
-fat
Do we store FAs?
no, FAs are acidic but we do convert them to fat and store fat
TGs break down to FAs. What is this called?
lipolysis/mobilization
Which hormone stimulates lipolysis?
glucagon
What is another name for lipolysis?
mobilization
Does lipolysis occur in a fed state or fasting state?
fasting state
FAs are broken down to acetyl CoA. What is this called?
B oxidation
Acetyl CoA can make cholesterol. What is this called?
cholesterologenesis or cholesterol biosynthesis
Cholesterol can be converted to steroids. What is this called?
steroidogenesis
Does cholesterologenesis/ cholesterol biosynthesis occur during fed state or fasting state?
fed state
Acetyl CoA can be converted to ketone bodies. What is this called?
ketogenesis
Does ketogenesis occur in a fed state or fasting state?
fasting state
What else can make acetyl CoA besides FAs?
carbs and AAs can also make acetyl CoA
Acetyl CoA can make FAs. What is this called?
lipogenesis
Which hormone stimulates lipogenesis?
insulin
Is lipogenesis during a fed state or fasting state?
fed state
Do we get FAs from our diet?
yes
FAs can make TGs. What is this called?
esterification
Why is lipolysis also called mobilization?
because you’re mobilizing fats
Mobilization/lipolysis is where lipases hydrolyze the TG stored in the adipocytes to produce….
FAs and glycerol
How do FAs gets from the adipocyte to the blood?
simple diffusion
How do FAs get transported within the blood?
bound with albumin
How does glycerol get to the blood from adipocytes?
simple diffusion
How does glycerol move within the bloodstream?
freely, does NOT need a carrier protein (glycerol is water soluble)
What hormones trigger lipolysis/mobilization first?
glucagon or epi interact with AC first and make cAMP to start cascade
note: you have to feel hungry and if you wait to eat then the fats will start to get mobilized
What is the RLE in lipolysis/mobilization?
hormone sensitive lipase, also known as TG lipase
note: it removes a FA from either carbon 1 or 3 (DG lipase will be used on DGs, and MG lipase will be used on MGs)
What is the active form of TG lipase?
with phosphate attached
Can FAs convert to glucose?
Short answer no, but glycerol can
Exception- out of all the FAs, only odd chain FAs can convert to glucose (bc of propionyl CoA)
After mobilization/lipolysis, 2 glycerols will go to the liver because of an enzyme to make glucose (2 glycerols are needed to make glucose). What enzyme is used?
glycerol kinase
2 glycerols with glycerol kinase will make 2 glycerol 3 phosphate (which then will make DHAP and GAP, then F6P. F6P will convert to G6P with F1,6BPtase. G6P will then convert to glucose with G6Ptase)
FAs can go to any tissue that does not require glucose (RBCs, adrenal medulla, CNS, and gametes require glucose). Where do FAs usually go?
to liver (albumin will be left behind in blood while FA can simply diffuse into liver)
Acyl means….
FA
What is the first stage of FA metabolism (lipolysis)?
-after entering a liver cell, free FAs are immediately converted to fatty acyl coA
-fatty acid + SHCoA (thio CoA) + 2 ATP undergo reaction with acyl CoA synthetase/thiokinase to make fatty acyl CoA and AMP
-this enzyme requires vitamin B5
-this process is called fatty acid activation
What is stage 1 of FA metabolism/ lipolysis called?
FA activation
Where is acyl CoA synthetase/thiokinase located?
in the cytoplasm of liver cells
What does acyl CoA synthetase/thiokinase require?
vit B5 and 2 ATP
What is fatty acyl CoA also known as?
FA-SCoA, acyl CoA, or acyl SCoA, palmitoyl CoA (this one specifically is also known as palmitate)
What is stage 2 of lipolysis/FA metabolism?
-basically- FAs transport to mitochondria
-this is for FAs that are 12+ carbons bc they need a carrier
-the carrier is carnitine and its a VIP molecule
-this stage is the rate limiting stage
-acyl CoA binds with carnitine with the help of carnitine acyl transferase 1 (CAT1) and the CoA will stay in the cytoplasm, whereas acyl carnitine will now be on the outer membrane of the mitochondria
-acyl carnitine will be transported to inner mitochondrial membrane and then undergo reaction with CAT2 and 1 CoA molecule to separate acyl and carnitine
-carnitine will go back out to cytoplasm and repeat, whereas acyl CoA will move onto beta oxidation stage
What is stage 3 of FA breakdown called?
beta oxidation of FAs
What is the beta oxidation stage of FA metabolism?
-an acetyl CoA is stripped off every turn of the oxidation spiral
-each turn generates 1 FADH2, 1 NADH, and 1 acetyl CoA
-there are 4 steps in 1 turn
What is generated after 1 turn of beta oxidation with a FA like palmitate?
-1 FADH2
-1 NADH
-1 acetyl CoA
What are the 4 steps of beta oxidation called?
1) oxidation/dehydrogenation
2) hydration
3) oxidation/dehydrogenation
4) thiolytic cleavage
What is step 1 of beta oxidation?
-its an oxidation/dehydrogenation step
-acyl CoA undergoes a reaction with acyl CoA DH to make 1 FADH2 and enoyl CoA
-this creates a double bond between the alpha and beta carbons
Which enzyme connects beta oxidation with ETC?
acyl CoA DH (its one of the enzymes that is a part of complex 2)
What is step 2 of beta oxidation?
-hydration reaction (add water)
-enoyl CoA undergoes a reaction with enoyl CoA hydratase to make L hydroxyacyl CoA
-the water in this reaction opens the double bond between the alpha and beta carbons that was previously made in 1st step
What is step 3 of beta oxidation?
-oxidation/dehydrogenation
-L hydroxyacyl CoA undergoes a reaction with hydroxyacyl CoA DH to make beta ketoacyl CoA and 1 NADH
What is step 4 of beta oxidation?
-thiolytic cleavage
-beta ketoacyl CoA undergoes a reaction with beta ketothiolase and SCoA to make acyl CoA (now 2 carbons shorter) and 1 acetyl CoA
-the bond between alpha and beta carbons were cleaved to create the acetyl CoA and acyl CoA
-beta oxidation will repeat starting from step 1 until the FA is completely broken down and generates 2 acetyl CoAs
How many carbons and/or double bonds does palmitate have?
16:0 (so its a saturated FA “SFA”)
How many rounds of beta oxidation does it take to fully break down palmitate?
7 rounds
How do you calculate number of rounds for even chain FAs?
total number of carbons / 2 and then subtract that number with 1
How many FADH2 are generated with palmitate breakdown?
7
How many NADH are generated with palmitate breakdown?
7
How many acetyl CoA are generated with palmitate breakdown?
8 (for even chains, add 1 to number of rounds to get # of acetyl CoAs generated)
How many ATP (net yield) are generated with palmitate breakdown?
129 ATP
How do you calculate ATP generated from NADH?
multiply number of rounds by 3
How do you calculate ATP generated from FADH2?
multiply number of rounds by 2
How do you calculate ATP generated from acetyl CoA?
number of rounds + 1 and then multiply it by 12
How do you calculate total ATP generated from FA breakdown
add together ATP generated from NADH, FADH2, and acetyl CoA
and then subtract total by 2 (because 2 ATP was used during activation step of FAs)
How many carbons and/or double bonds does stearate have?
18:0
How many ATP are generated from 20:0?
How is beta oxidation of unsaturated FAs different from the usual saturated FAs?
for each double bond in a FA, one less FADH2 is generated
How is beta oxidation of odd chain FAs different from saturated or unsaturated FAs?
all the steps are the same HOWEVER there is a different end product- instead of 2 acetyl CoAs at end there will be 1 acetyl CoA from that round and a propionyl CoA
for an odd chain unsaturated FA the NADH and acetyl CoA will be the same number as the turns but the FADH2 will be different because 1 less FADH2 is generated per double bond
Which FA chain make glucose?
ONLY odd chain fatty acid bc of the propionyl CoA
even chain or unsaturated chains cannot
Odd chain FAs are the only FAs that can make glucose because of propionyl CoA. to do this, propionyl CoA will undergo a reaction with what enzyme to make methylmalonyl CoA?
propionyl CoA carboxylase
Odd chain FAs are the only FAs that can make glucose because of propionyl CoA. to do this, propionyl CoA will undergo a reaction with proprionyl CoA carboxylase to make methylmalonyl CoA. What is required here?
-ATP
-vitamin B7/ biotin
-carbon dioxide
Odd chain FAs are the only FAs that can make glucose because of propionyl CoA. to do this, propionyl CoA will undergo a reaction with proprionyl CoA carboxylase to make methylmalonyl CoA. Then methylmalonyl CoA will undergo a reaction with what enzyme to make succinyl CoA (which will then go to TCA and then eventually convert to glucose)?
methylmalonyl CoA mutase
Odd chain FAs are the only FAs that can make glucose because of propionyl CoA. to do this, propionyl CoA will undergo a reaction with proprionyl CoA carboxylase to make methylmalonyl CoA. Then methylmalonyl CoA will undergo a reaction with methylmalonyl CoA mutase to make succinyl CoA (which will then go to TCA and and then eventually convert to glucose). What does methylmalonyl CoA mutase require?
vit B12/ cobalamin
Any reactions with a carboxylase will require what?
ABC
-A= ATP
-B= biotin/ vit B7
-C= CO2
If theres an increase in methylmalonyl CoA, then what will it become and what does this indicate?
-indicates vitamin B12 deficiency/ cobalamin
-methylmalonyl CoA will be converted to methylmalonate in the blood (can be detected in blood test)
What 2 things did we talk about that cause a vitamin B12/ cobalamin deficiency?
1) strict vegetarians bc B12 is only found in animal products
2) intrinsic factor deficiency (common in 50+ y/o)
When theres a B12 deficiency and/or biotin deficiency, then there will be an increase in propionyl CoA in the body and this can lead to….
damaged myelin/demyelination which will ultimately cause peripheral neuropathy
How is lipolysis regulated?
1) fat mobilization is regulated by TG lipase
2) malonyl CoA inhibits CAT1 which inhibits beta oxidation by preventing acyl CoA from entering the mitochondria
3) high citrate levels inhibit beta oxidation (because once citrate levels are high it means the body needs FAs so they shouldn’t be broken down)
Fat mobilization is regulated by what?
TG lipase
What inhibits CAT1 and therefore inhibits beta oxidation by preventing acyl CoA from entering mitochondria?
malonyl CoA
High levels of what molecule inhibits beta oxidation?
high levels of citrate (because once citrate levels are high it means the body needs FAs so they shouldn’t be broken down)
