FA II Flashcards
FA are made in the cytosol. If they need to be longer, we send them to the _____ or ____.
- SEr
2. Mitochondria
In the blood, _____ must be tagged with albumin to keep them from clumping.
LCFA must be tagged with albumin to keep them from clumping.
There are 2 steps to FA degradation
- FA movement inside the MT
2. B Oxidation
_____ and ____ can diffuse into the mitochondria. However, the outer MT membrane is impermeable to _____.
short chain FA and medium chain FA can diffuse into the membrane. However, the outer MT is not permeable to LCFA and VLCFA.
How do we combat the fact that LCFA are not permeable to the outer mitochondrial membrane?
ADD A ACYL COA
Step 1 Steps
As we have said, the outer membrane is not permeable to LCFA.
So:
1. FA–[Fatty acyl CoA synthetase]–> Fatty Acyl CoA
Fatty Acyl CoA can now cross the membrane into the intermembrane space. But now, there is a problem, it cannot cross the inner mT membrane
This required 1 ATP
- So we want to remove the Co-A and add a carnitine. Adding a carnitine is its right of passage into the matrix.
Fatty Acyl CoA–[CPT-1: carnitine palmitoytransferase I]–> Fatty Acyl Carntine.
CPT-1 is the rate limiting enzyme in FA breakdown.
- Fatty acyl carnitine can now move into the matrix via CACT (carnitine shuttle)
Carnitine shuttle is an antiport. It moves Fatty acyl carnitine into the matrix and moves carnitine out - Fatty acyl carntine is now acted upon by CPTII to remove the carnitine and change it back to Fatty acyl coA
Shortcut of phase 1
To get past outer MT membrane: 1. add a coA To get past the inner MT membrane 2. add a carnitine Once inside 3. remove carnitine and add a coA again.
Where is fatty acyl coA synthetase located?
on the outer membrane
What is CPT-1
Carnitine palmitoytransferase will remove the coA and add a carnitine. Located in the inter mT membrane
What is CACT
CACT is the carnitine shuttle that will transport fatty acyl carnitine to the mitochondrial membrane.
It is an antiport and remove the build up of carnitine from inside the matrix
What is CPT-II
Removes carnitine and adds coA
Where is CPT-1 located
intermembrane space
Where is CACT located
inner mt membrane
where is CPT-II located
inner mt membrane
What is the rate limiting enzyme in FA breakdown?
CPT-1
Carnitine palmitoy transferase!
Our typical saturated FA have how many carbons
an even number
16-20
What do we make in B oxidation?
- Acetyl Co-A- taken into the TCA cycle
- NADH–> move electrons to complex 1
- FADH2–> move electrons of coQ
B oxidation makes 3 things: what is it?
- Acetyl CoA
NADH
FADH2
What is the first substrate of B-oxidation?
Fatty Acyl Co-A
Acroynm for B oxidation
OHOT oxidation hydration oxidation thiolysis
Oxidation
ACAD (acyl coA dehydrogenase) will oxidize Fatty acyl coA
FADH2 is made
Why is ACAD important
it causes many disease
Hydration
NADH is made
2nd oxidation step
Acetyl CoA is released
The only enzyme to remember in B oxidation is
ACAD
Acyl Co-A Dehydrogenase
B oxidation occurs where?
mT matrix
Types of ACADS
4 types
- SCAD
- MCAD
- LCAD
- VLCAD
______ is the type of ACAD that causes the most diseases
MCAD
medium chain acyl coA dehydrogenase
What happens if we have a FA with a odd number of carbons?
Phase 1- same.
However, if we break it down, we will be left with a 3 carbon compound known as PROPIONYL COA.
So what do we do?
PROPIONYL COA.–[propionyl coA carboxylase]–> methylmelonyl coA (a 4 carbon compound)
methyl melonyl coA will eventually become succinyl coA and go into the TCA cycle
3 carbon compound created when oxidizing odd numbered FA
propionyl coA
What would we do to proponiol coA
carboxylate it via propionyl coA and make a 4 carbon compound called methmalonyl coA
What happens to the methyl-melonyl coA made?
it will eventually become succinyl coA and enter the TCA cycle
What happens if we are trying to break down unsaturated FA?
We will need new enzymes. We metabolize it until a DB is reached
- Reducatases will reduce the DB
- Isomerase will move the disrupted bond so it can be degraded by a regular enzyme
How are VLCFA–> LCFA
perixisomal B oxidation
once you get to 20 carbons, it undergoes normal oxidation
When you are undergoing B oxidation in the perixoisome, do you make energy?
NO. You do not make any NRG.
High energy electrons are transferred to O2 to make H202.
If you undergo B oxidation in the perixisome, wont it create a build up of H2O2?
No. A catalase will then convert the H2O2 to water and O2.
Key difference in peroxisomal B oxidation and regular?
During the 1st oxidation stage, ACAD is not used.
It will use Acyl CoA Oxidase, which still creates FADH2, but not for NRG. electrons are transferred to O2 to make H2O2
What enzyme is used instead of ACAD in perixosomal B oxidation?
Acyl CoA Oxidase
Zellweger syndrome
patient has a defect in the generation of peroxisomes. Thus, they cannot break down VLCFAs
MCAD deficiency
People with MCAD deficiencies cannot break down medium chain FA.
It leads to a secondary deficiency in carnitines because we rare excreting a lot of it out. We are soaking up alot of our carnitines.
Person will have elevated levels of ammonia
Pts will depend on glucose for NRG.
This is preventative
Ketone bodies are made when we have a lot of _______
acetyl coA
What begins the creation of ketone bodies?
Ketone bodies are made when we have a problem with insulin signaling (people with DB or on a ketogenic diet). Glucose is not getting into the cells; so we cannot use it for energy.
As a result, we start to use our fat stores. Fat is broken down and is made into acetyl coA
We then get a build up of acetyl coA, which will then make ketone bodies.
Where are ketone bodies made/
ONLY the mT matrix of the LIVER!!!!
Characteristics of ketone bodies
- acidic
2. water-soluble
3 types of ketone bodies
- acetoacetate
- acetone
- beta- hydroxybutryate.
What can use ketone bodies?
- brain
- muscles
- kidneys
Can RBCs use ketone bodies?
NO!
How can we create acetoacetate?
2 acetyl coAs combine–> acetoacetyl CoA–>
HMB CoA–> Acetoacetate
few hours after fasting
- blood glucose
- glycogen stores
- gluconeogenesis
1 day after not eating
B oxidation of TAGS
3 days after eating
- begin to make ketone bodies
- proteins in muscles break down
- glycerol from TAGS and proteins enter glucogonic AA enter gluconeogenesis can provide NRG to the brain and RBC
1-2 weeks after
brain will use ketone bodies
2-3 months
death
When can we get physiological ketosis?
slight elevation of ketone bodies
occurs when fasting, pregnant, excercising, babies and ketogenic diet
Pathological ketoacidosis
Glucagon/insulin ratio is increased and we favor FA breakdown
in diabetic ketoacidosis
ketones are being formed and they drop your blood pH big time
What does CACT stand for
Carnitine acylcarnitine translocate (CACT) shuttles fatty acyl carnitine into the matrix
why do we die from ketone bodies
blood pH drop
