Fatty Acid Transport and Beta Oxidation - Ch. 30 Flashcards
L carnitine is converted to ____ which contributes to the formation of __.
TMAO - transmethyl amine oxide; atherosclerosis -> cardiovascular disease
What do Long chain FA need to enter into the plasma membrane?
They need to bind to albumin (proteins that act as a carrier)
Where do long chain fatty acids come from? What is the end goal
Adipocytes; convert to acetyl coA and make NADH and FADH2
Long Chain FA are soluble in water. True/False?
False, they are insoluble (that is why they need FA binding proteins)
How do FA get activated to be able to enter the outer mitochondrial membrane? What do they turn into that enters the outer membrane (intermembrane space)?
Coenzyme A; Fatty Acyl CoA
How does FA get into the inner mitochondrial membrane (inside the middle of the mitochondria)?
CoA comes off and carnitine (shuttle into inner mitochondria) replaces it. Then carnitine comes off once inside (back to a fatty acyl CoA)
Serum albumin can bind how many FA? What else can it bind? Why?
6; hormones and drugs; bc its nonspecific
FA entry into cells can be ___.
regulated (but we wont worry abt this)
How do all FA get into cells? And where could they go into?
They use a saturable binding protein and free diffusion (to get into mitochondria, peroxisomes, ER)
Are synthases = synthetases?
Synthetases CONSUME ATP, but they are a type of synthase (usually interchangeable)
A Very Long chain is how big (#)?
about 14+ but varies
How many isoforms of Fatty acyl CoA synthetase exist?
4
Acetyl CoA gets used where/how?
To make KB in the liver, and make more NADH, FADH2, 2CO2 in the TCA cycle
The intermediate between FA and fatty acyl CoA is? How is this possible?
Fatty acyl AMP (covalent) + pyrophosphate ; FA synthetase uses a nucleophile oxygen from carboxyl group to attack the FA oxygen
Activating FA CoA requires how much ATP?
2ATP (because AMP is generated)
After a Fatty acyl CoA has been activated and crosses the plasma membrane of the cell, where do MC Fatty acids end up?
Medium chain FA are in the matrix
After a Fatty acyl CoA has been activated and crosses the plasma membrane of the cell, where do LC Fatty acids end up?
Long chain FA are in the outer layer
After a Fatty acyl CoA has been activated and crosses the plasma membrane of the cell, where do Very long chain FA synthetases interact with them?
very long chain- peroxisomes
After a Fatty acyl CoA has been activated and crosses the plasma membrane of the cell, where are Short chain FA synthetases they interact with?
In the cytosol
What organelles of the cell are used to make energy from Fatty acids?
peroxisome (VLC) and mitochondria (LC, MC)
How do medium chain FA travel into mitochondria?
Using monocarboxylate transporters (context of lactate and KB?). they are then activated to fatty acyl coas and do b ox.
What does the ER have to do with FA? (location, function)
Not only are LC FA synthases on outer mitochondrial layer, but they are on the ER too! The ER’s job is to store and create membrane lipids
The ER’s job is to store and create membrane lipids . Which ones?
phospho and sphingo lipids are membrane lipids, and triacylglycerols are for storage
What is carnitine synthesized from in our bodies? Where else do we get it?
From lysine; diet (mostly red meat)
Carnitine deficiencies are rare, T/F?
TRUE
Gut microbes generate tri methyl amine from
_-carnitine and ___
from L carnitine and choline ( a head group)
An oxidase in the liver converts TMA to TMAO, causing reverse __ transport->___.
cholesterol; hypercholesterolemia because of decreased bile acid making
How can we prevent atherosclerosis?
allicin in garlic, antibiotics
The beta oxidation spiral happens in the _. How many acetyl Coa’s are formed (repetition)?
mitochondrial matrix; 6 repetitions make 7 total
How do you know if a FA got activated to become a acetyl coa
2 carbons got cut off (16->14)
In the FA oxidization spiral, which carbon is targeted? What enzyme does this?
The beta carbon (2nd from the carbonyl C-C-=O-C); Acyl CoA dehydrogenase
How many isoforms of acyl CoA exist
4 (depends on chain length, vlc, lc, mc, sc)
What is the order of the b oxidation spiral steps?
oxidation, hydration, oxidation,
The first step of the b oxidation cycle yields __. where does it go?
FADH2 and 1.5 ATP; FADH2 directly goes into TCA without leaving acyl coa dehydrogenase
The third step of b oxidation yields
NADH and 2.5 ATP
An alkene has how many bonds? An alkyne?
2; 3
For long chain fatty acids, once they go into the porous outer mitochondrial membrane, they become a substrate for ___. What does this enzyme do?
Carnitine: palmitoyl transferase I (CPT I) transferase; it takes off CoA and puts a carnitine in its place
What is the antiport process in long chain fatty acid transport?
The antiport process is the movement of fatty acyl carnitine in and carnitine:acylcarnitine translocase send it out of the matrix.
What is the job of carnitine:palmitoyl transferase II (CPT II)?
It takes carnitine off the fatty acyl carnitine and replaces it with CoA. then fatty acyl coa is born! (and can go into beta oxidation)
primary CPT I deficiency causes __ in the blood
increased blood FA
primary CPT II deficiency causes ___
elevated blood acylcarnitine, increased blood FA
As a FA chain goes through the b oxidation spiral, what happens?
they become substrates for different acyl coA dehydrogenases
When would thiolysis go in the reverse direction? Why?
when lots of acetyl coa (can make acetoacetate in the ketone synthesis pathway or get used in cholesterol synthesis)
Unsaturated FA can be beta oxidized using
additional enzymes - enoyl CoA isomerase and 2,4 dienoyl coa reductase (idt we need to know)
most fatty acids from our diet and in adipose tissue are __. they use __ system.
long chain; carnitine transport
When we consume fiber, gut bacteria convert it to
short chain fatty acids
short chain fatty acids examples are
acetate, propionate, butyrate
short chain fatty acids have benefits such as
better immunity and metabolism, food for colonocytes that are ox by liver for energy
Which products are rich in medium chain FA?
dairy, coconut/palm oil
Describe the last repitition of an even chain fatty acid going down the b oxidation spiral
4 C chain = butyryl CoA does 1 last repetition of the spiral. the second to last step makes acetoacetyl CoA, and the last step of the spiral is thiolysis, creating 2 CoA molecules
How many carbons are left on before the last step of a odd chain beta oxidation spiral? what are we left with after?
5; propionyl coa
Propionyl coa is a __ process in the __
anaplerotic (refilling); tca cycle
Proionyl coa gets converted to __ inthe ___ pathway
succinyl coa in the vomit pathway
Where are FA oxidation for LC happening organ wise?
is it the liver? liver adipocytes?
FA made outside the liver are used for? what types are these?
membranes; VLC, MC, SC
MC and SC Fatty acids are not stored in adipose. rather, where do they go?
they get moved directly to liver or other organs for oxidation
medium chain fatty acyl CoA synthetase also recognizes
drugs with carboxyl groups
You can do some __ with odd chain fatty acids because
gluconeogenesis; succinyl coa is made and fed into the tca cycle
The first step of propionyl coa -> succinyl coa requires what enzyme and substrate?
propionyl coa carboxylase; biotin
The second step of propionyl coa -> succinyl coa requires what enzyme and substrate?
methylmalonyl coa epimerase (d methylmalonyl coa to l methylmalonyl coa)
The third step of propionyl coa -> succinyl coa requires what enzyme and substrate?
methylmalonyl coa mutase needs b12; l methylmalonyl coa->succinyl coa
biotin is a substrate that activates __ for a carboxylase enzyme to do its job
co2 (inside hco3-?)
Why is methylmalonyl coa mutase significant?
1 of 2 enzymes that need b12
How are acylglycines targeted?
they are a marker for elimination (esp in liver->GI->feces or resorb by renal sys->urine)
A defect in fatty acyl coa dehydrogenase causes … to accumulate; where ?
accumulated fatty acyl coa’s and fatty acyl carnitines to show up in the urine and serum
The CoA adduct made by MC acyl CoA synthetase is turned into acylglycine by which enzyme
glycine N acyltransferase
Sometimes FAcyl CoA that accumulate with CPT disorders can be substrates for __. Which direction?
CPT II in the direction of making carnitines instead of break down (reverse rxn). This reverse reaction generates CoA-SH to use elsewhere for TCA
