FA-I Flashcards
What stores more energy: TAGS, Carbs or proteins?
TAGS store 7x more NRG than carbs
Do we break down proteins for NRG?
No. We do not.
______ are designed to store!
TAGS
What are the two lipid classifications
- FA derivatives
2. Isoprene derivates
Storage form of fats is
TAGS
Glyceral backbone with 3 FA
How can we be fat if our fat intake is low?
The carbon that we use for FA synthesis actually comes from CARBS!
CARBS r BaD
What is the precursor for FA synthesis?
acetyl co-A
When is fat storage initiated?
After a big meal;
when insulin and glucose are HIGH!
What part of the cell does fatty acid synthesis occur?
Cytosol
Where does FA synthesis occur?
5 place:
- liver
- fat tissue
- brain
- kidneys
- mammary glands
acetyl co-A has how many carbons?
2
What are the phases of FA synthesis?
- Move acetyl-CoA out of the mitochondria matrix–> cytosol
- Make Malonyl Co-A, the most important substrate in FA synthesis
- FA chain formation
- Acetyl-CoA entrance into the cytoplasm
- Acetyl Co-A combines with OAA to form citrate via citrate synthase
- Citrate is then take out of the cell using citrate synthase
- Citrate is then broken down to [OAA and acetly coA] via ATP Citrate Lyase
- OAA–> malate via malate DH.
Malate can now do 2 things:
- Use a transporter–> mT matrix
- Convert to pyruvate
Is there an acetyl co-A transporter?
No
Was the concentration of OAA in the mitochondria altered?
No, because we returned it.
ATP Citrate Lyase is stimulated by
high glucose
high insulin
in other words, FA synthesis is activated by glucose and insulin
ATP citrate lyase is inhibited by
PUFA
Leptin
Summary of Moving Acetyl Co-A into the cytosol
Acetyl coA will combine with OAA in the mT matrix to form citrate via citrate synthase.
citrate transporter moves citrate out of the cell
in the cytoplasm, citrate is broken back down to OAA and acetyl co-A using [ATP citrate lyase]. ATP is used.
OAA needs to be taken out. It is converted to malate via malate DH. 2 fates for malate:
1. taken back to mt matrix via the malate transporter
- converted to pyruvate
- Create Malonyl CoA
[Acetyl co-A]–> [malonyl coA] via ACC (acetyl coA carboxylase).
ATP is used and ACC needs a biotin cofactor
Acetyl co-A is 2 carbons and is made into a 3 carbon malonyl coA via a carboxylation
**RATE LIMITING enzyme
What does ACC stand for
acetly coA carboxylase
ACC needs what kind of cofactor
biotin
Why is malonyl coA so important?
malonyl coA is the substrate for FA synthesis! and its the rate limiting enzyme
When malonyl coA is present, what will it inhibit?
carnitine acyltransferase. this is the rate limiting enzyme for FA degradation
_________ prevents FA synthesis and degradation from occurring at once
Malonyl-coA
- Chain elongation
Carbons are added two at a time to a growing chain via [fatty acid synthase].
Fatty acid synthase will add 2 carbons from malonyl coA to a growing chain
What does fatty acid synthase do?
Fatty acid synthase is responsible for chain elongation.
Structure of FA synthase
FA synthase is a large multi-enzyme complex with 2 identical dimers.
Each dimer has 7 enzymatic activities and an ACP (acyl carrier protein)
ACP
Acyl carrier protein
an arm on FA Synthase made up of phosphopantotheine that carries to each rxn.
FA Synthesis via FA synthase acronym
Condensation
Reduction
Dehydration
Reduction
Condensation by FA synthase
malonyl group and an acetyl group are added together to make a 4 carbon compound.
1 carbon is lost as a CO2.
Reduction in FA synthase
NADPH–> NADP+
What is happening in condensation?
A acyl group and malonyl group are being combined to form a 4 carbon compound. 1 compound is lost a CO2
FA Synthesis requires a lot of ________
NADPH
Where does the NADPH for FA synthesis come from?
- Malic enzyme (converts malate to pyruvate) uses 1
2 PPP uses between 2-12 NADPHs
What is being reduced in FA Synthesis: chain elongation
NADPH
What is the rate limiting enzyme in FA synthesis?
ACC
Acetyl Co-A carboxykinase
Regulation of ATP citrate lyase
3
ATP Citrate Lyase is
- Stimulate when it is phosphorylated.
- inhibited by PUFAs. Polyunsaturated FA will inhibit the gene expression of ATP Citrate lyase. SO YAY LETS EAT MORE!
- Leptin will also inhibit ATP Citrate Lyase bc why store fat if we are full and have stopped eating
ATP Citrate Lyase is activated when?
Phosphorylated
Do we want to eat more or less PUFAs?
MORE! PUFAs inhibit the gene expression of ATP citrate lyase
ATP Citrate Lyase is affected by what things:
- Glucose
- Insulin
- PUFAs
- Leptin
- Phosphorylation
When is ACC active?
ACC= acetyl co-A carboxylase.
ACC is active when it is DEPHOSPHORYLATED.
The longer ACC is, the more active!
Thus, ACC is not active as a dimer, but it is active as a polymer
Is ACC active as a dimer?
No
Is ACC active as a polymer?
YES!
ACC allosteric activators
Citrate. If we have a lot of citrate, we want to store it!
ACC allosteric inhibitors
LCFA (long chain fatty acids).
We can only make FA so long
Epinephrine, glucagon and insulin will do what to ACC?
inhibit it using a kinase (because ACC is active when it is dephosphorylated).
What will a high carb, low fat diet do to ACC production.
High carb= more carbons to add to fatty acids.
So a high carb, low fat diet will PROMOTE the production of ACC.
2 things allosterically regulate ACC. What are those two things?
- Citrate (+)
2. Long chain FA (-)
If we have a lot of phosphorylated sugars present, how will this affect the activity of FAS?
Allosterically affect them. We will want to store them as fat
How does a glucocorticoid diet affect FAS?
Synthesis of FAS will increase
A high fat diet will do what to FAS?
Decrease the synthesis.
A high carb diet will increase synthesis of FA.
Order of active enzymes
ATP Citrate Lyase- phosphorylated
ACC- dephosphorylated
What is leptin?
Leptin is a hormone released from fat tissue that tells us we are full.
It binds to receptors on the hypothalamus to help regulate our weight.
What would happen if we did not have leptin
Our body would not when if we are full. Therefore, we would be fat and never stop eating ,
How can we make a FA chain longer?
If we want to make a FA chain longer,
We will have to move our FA from the [cytosol]–> to one of two places
- Smooth ER
- Mitochondria.
For this to happen, we have to reduce NADPH to give us the energy to add carbons. Where do we get the carbons from?
sER will use malonyl coA.
But the mT, being the big strong mn he is is, will use acetly coA
FA chains can only be made longer where?
- Smooth ER
2. Mitochondria
To make a longer chain, where do we get our NRG from?
The reduction of NADPH will give us the NRG to add carbons!
Where do we get this carbon from tho?
sER–> malonyl coA
mitochondria–> acetyl coA
When we make unsaturated fats, this is called _________
Desaturation
Desaturation (the making of unsaturated FA) occurs in the _____
Smooth ER
Making long chain FA and unsaturated FA occur in one common place:
Smooth er!
What enzyme makes DB in fatty acids?
Acyl-coA Desaturases
Role of acyl coA desaturases
Acyl co-A desaturases will introduce DB into FA to make them unsaturated.
DB can only be introduced in what positions?
4,5,6,9
How do we count where the DB is on a FA
Start from the carboxyl side with 1
Can we make DB beyond the 9th position?
No, we cannot. We have to cosume these in our diet
How are omega FA named
Omega FA are unable to be made by humans.
We have to get them from our diet. So, if there is a DB past thr 9th position, we know its omega.
to make, you start counting at the omega (methyl end)
How many desaturases do humans have?
4
one to introduce at 4, 5, 6 ,9
What are essential FA
Essential FA are those that we cannot make because they have a DB past the 9th carbon.
Thus, we must get them from our diet or ingest their precursors. (w-3 and w-6).
Precursor for w-6
Linoleic acid–> precursor for arachidonic acid (w-6)
Precursor for w-3
linolenic acid–> precursor for w-3
EPA and DHA
Insulin induces/does not induce the expression of desaturases
does
PUFAs inhibit/ do not inhibit desaturases
do inhibit
Cholesterol and desaturases
Cholesterol will induce the expression of 9 desaturase and supress the others!
