Fatty Acid Metabolism Flashcards
What is the purpose of fatty acid oxidation?
Generate energy
Describe the GENERIC pathway of Fatty Acid Oxidation
- ____________ become ______ and mobilize from __________.
- _________ get _______,____ and go through _________ in the ______ to become ____________.
- ______ enters the _________ to produce _______ and then the _______ to create ________ and ______.
There is an alternative pathway. Describe it.
- Lipids become fatty acids and mobilize from adipose tissue.
- That acids get activated, transported to the blood and go through beta oxidation in the mitochondria of a kidney or liver cell to become acetyl-CoA
- Acetyl-CoA enters the TCA/citric acid cycle to produce NADH/FADH2, and then the electron transport chain to create H2O and ATP
Acetyl-CoA in liver can become a ketone body, enter non-hepatic tissues, be converted back to Acetyl-CoA and be used in the TCA and ETC.
_____ of lipids are stored in the _____ as ______.
99% of lipids are stored in the adipose tissue as TRIACYLGLYCERIDES
What two tissues does fatty acid metabolism take place in most often?
Kidney, Liver, Muscle ,Heart
Remember that glycogen is mostly stored in muscle and liver!
Where is fatty acid metabolism LOW ?
Brain and nervous tissue
The majority of glycogen is stored in __________.
Muscles and Liver
What is Step 1 of fatty acid oxidation? Describe it
- Fat Mobilization ( Adipocyte to Blood)
Fat mobilization is enhanced during starvation or fasting. When glucose levels are low, glucagon levels will increase to stimulate adenylate cyclase protein on ADIPOCYTES.
Adenylate cyclase will stimulate triacylglycerol lipase (hormone sensitive lipase) to cleave ester bonds within triacylglycerol molecules stored in the cytosol of adipocytyes to make fatty acids and glycerol.
The cleaved portions of fatty acids can now exit the adipocyte via the plasma membrane into the blood.
LECTURE SLIDE POINT
Fatty acid metabolism is low in the _____ but high in _______.
brain, muscle
What are the different type of fatty acids? Describe their structural differences.
Short Chain FA 2-3 carbons in acyl chain
Medium Chain FA 4-12 carbons
Long Chain FA. 13-20 carbons
Very Long Chain FA. >20 carbons
Fatty acids contain several ____ groups making it _____ and ________.
After Step 1 of the fatty acid oxidation mechanism, we have delivered our fatty acid fragments to the _________.
Since _______ do NOT ________ in ______, how do we transport the fatty acids to other tissues?
Step 2!
CH, non-polar and hydrophobic
blood
fatty acids, do NOT dissolve in blood
Albumin in blood helps transport LCFA from adipocytes to other tissues!
FA can bind to albumin to form a water-soluble compound. The FA-albumin complex will combine with the Fatty Acid Binding Protein to travel across the plasma membrane of a liver cell (or heart, muscle,kidney) into the cytosol
What is the most abundant protein in the blood?
Albumin
What is Step 2 of fatty acid oxidation? Describe it
Since FAs are not water-soluble, albumin in blood will combine with FAs to form a water soluble complex. Fatty Acid Binding Protein will shuttle the FA-albumin complex across the cell membrane of heart,kidney,liver or muscle cells into the cytosol once the complex approaches the cell.
In Step 2 of fatty acid metabolism, our fatty acids have been relocated to the __________. Step 3 of this process is the _____________ of _______ which occurs in the _______________.
cytosol of a tissue cell
beta-oxidation of fatty acids, mitochondrial matrix
What is Step 3 of fatty acid oxidation? Describe it
In Step 2, our fatty acids have been shuttled to the cytosol of a tissue cell. Now it must go through an activation process to enter the mitochondrial matrix.
First, Fatty Acid will be oxidized to Fatty acyl CoA by using an enzyme located in the outer mitochondrial membrane.
Fatty acyl CoA can travel through the OUTER mitochondrial membrane to enter the inner membrane space but cannot diffuse through the inner mitochondrial membrane because it is tightly packed.
In order to travel into the Matrix through the inner mitochondrial membrane, the Carnitine Transport System is necessary.
What is the Carnitine Transport System? Which Step of __________ is it associated with?
Describe the enzymes associated!
Fatty-acid oxidation, Step 3
The process by which fatty acyl CoA is transported from the inner membrane space to the matrix via the inter mitochondrial membrane.
- Carnitine Palmitoyl-Transferase I (CPT 1)
Converts Fatty Acyl CoA to Fatty acylcarnitine (cleaves CoA)
- Carnitine Acylcar Nitine Translocase
Transports Fatty acylcarnitine to Matrix
- Carnitine Palimotyl Transferase II ( CPT II)
Convert fatty acid carnitine back to Fatty Acid CoA
Where else can beta-oxidation of fatty acids occur besides the mitochondria? What is the key difference?
Perioxosomes
NO ATP produced because there is no ETC in perioxosomes.
All fatty acids must use the carnitine transport system. True or False
FALSE
Short Chain FA can pass through the Inner Mitochondrial Membrane independently!
The Carnitine system is reserved for LCFA and VLCFA.
Acetyl-CoA can also be used to make ___________ in the ______.
What is generated as a product as well? Why is it important?
Acetyl-CoA can be used to make fatty acids such as LCFA in the cytosol. In this process, we generate a lot of Malonyl CoA as well.
Malonyl CoA will inhibit CPT I by not allowing the formation of Fatty acylcarnitine from Fatty Acyl-CoA
If fatty acid synthesis is active, fatty acid oxidation is ______.
Inactive
What are the three types of fatty acid oxidation? Which one is most important?
Alpha - most proximal to carboxyl carbon next to CoA
Beta
Omega - Most distal to CoA (terminal carbon)
(in Fatty acyl CoA)
BETA-OXIDATION
Describe the generic steps of beta oxidation
- acyl CoA dehydrogenase adds a double bond between the alpha and beta carbon.
- enoyl CoA hydralase adds water to create an -OH bond on the beta carbon (alpha beta carbon bond is back to one).
- B-hydroxy acyl CoA dehydrogenase oxidizes the - OH to =O
- Beta-keto thiolase cleaves the molecule into ONE molecule of Fatty acyl CoA and One molecule of Acetyl CoA
** ONLY RESPONSIBLE FOR STEP 1 ENZYME)
What are the final products of beta oxidation?
Fatty acyl CoA and Acetyl CoA
FADH2 and NADH which go to ETC
Acetyl CoA goes to TCA
The Fatty Acyl CoA produced by the beta oxidation is _____ carbons ____ than the Fatty Acyl CoA inputted because it looses a _______ during the __________.
The Fatty Acyl CoA will return to the beginning of the __________.
2 carbons shorters
Acetyl CoA , cleavage step involving Beta Thiolase
beta oxidation cycle
If the original fatty acid CoA contains an even number of carbons without branched groups, what is the fate of the entire molecule in beta oxidation?
The cycle will continue until only a single compound of Acetyl CoA is produced.
Remember we loose 2 carbons for every Acetyl CoA produced during cleavage.
Why is acyl CoA dehydrogenase so important?
Aside from adding a double bond between the alpha and beta carbon of Fatty Acyl CoA during beta oxidation, acyl CoA dehydrogenase related to biomedical issues.
What can inhibit ___________, the first enzyme involved with the beta oxidation cycle?
acyl CoA dehydrogenase
Hypoglycin (found in unripe ackee fruit)
Can cause vomiting, drowsiness, convulsions, coma, hypoglycemia, death
Which two steps of the beta oxidation cycle generate important compounds? What are they?
Where do these compounds go after production?
Step 1 involving acyl CoA dehydrogenase (FAD+ to FADH2) - 2 ATP
Step 3 involving involving another dehydrogenase (NAD+ to NADH) -3 ATP
FADH2 and NADH go to the ETC!
How does beta-oxidation of fatty acids change with odd chain fatty acids?
- The same activation process occurs as will regular FAs.
(Adenylate cyclase activation to push triacyglycerol lipase to cleave FA , fatty acids join albumin in blood to enter cell and go through a series of modification to enter the cytosol via Carnitine Transport (if needed)
- Beta oxidation occurs as usual in the matrix. The difference is in the products.
Odd chain fatty acids produce Acetyl CoA and Proplonyl CoA which has 3 carbons. Proplonyl CoA can be made into Methylmalonyl CoA and EVENTUALLY Succinyl CoA which can enter the TCA.
What is the final product of odd chain fatty acid beta oxidation?
Acetyl CoA- TCA
Proplonyl CoA which becomes Succinyl CoA - TCA
Describe the energy output of the beta oxidation cycle per molecule produced.
Per round of beta oxidation (cleavage of ONE carbon bond)
2 ATP per FADH2
3 ATP per NADH2
12 ATP per Acetyl-CoA
17 ATP per beta oxidation - (ATP for activating fatty acid)
(MINUS Energy needed to activate fatty acid to fatty acid-CoA)
Palmitate has 16 carbons. What is the final energy output after beta oxidation of the whole thing.
16 carbons
16C———————-1C-COO-
IGNORE C attached to OO-
Alpha carbon to the 16th carbon requires 7 cuts so 7 rounds of beta oxidation
7 FADH2 x 2 ATP = 14 ATP
7 NADH x 3 ATP= 21 ATP
8 Acetyl CoA x 12 ATP = 96 ATP
MINUS 2 for activating palmitate to Palmitoyl- CoA
129 ATP
Why does a 16 carbon fatty acid produce____ molecules of Acetyl-CoA if _____ rounds of beta oxidation are happening?
8 ,7
Each round of beta oxidation produces 1 Acetyl-CoA except for the last round which produces one additional one.
Simply do Cuts +1 to find the number of acetyl groups.
Where does ketone body formation occur and what is the starting molecule?
Mitochondrial matrix
Aceytl Co-A from fatty acid metabolism
What is the ketone body produced in the mitochondrial matrix ?
Acetoacetate
What is the major enzyme involved in ketone body formation ? Where is the most abundant?
HMG CoA Synthetase
Liver! So acetoacetate ketone body formation occurs alot here
What is the rate limiting enzyme in ketone body synthesis?
HMG CoA Synthetase
What are other types of ketone bodies?
beta-hydroxybutyrate
Acetone
Acetone can ______ in the _________.
evaporate, lung tissue
How is beta-hydroxybutyrate formed?
Acetoacetate of ketone body formation is converted via beta hydroxybutyrate dehydrogenase.
How is acetone formed?
Spontaneous! CO2 is a byproduct of converting acetoacetate to acetone
The pkas of ketone bodies are _____. What can the over production of ketone bodies cause?
low which means they are acidic
ketoacidosis; as it will lower blood ph from 7.4 to 6.8
Which of the ketone bodies are used to make energy?
Acetoacetate and Beta-hydroxybutyrate
Why are ketone bodies necessary?
Ketone bodies produced in the liver can diffuse quickly into the blood are utilized as energy fuels in non-hepatic tissues.
How is acetoacetate , a _______, used to make energy?
ketone body
Acetoacetate is converted to AcetoaceytlCoA or AcAcCoA via the thiotransferase enzyme.
Thiolase cleaves the AcAcCoA into 2 acetyl CoA molecules which can then enter the TCA cycle to produce energy.
What is the key enzyme involved in using ketone bodies to make energy?
Thiotransferase
Thiotransferase is _______ in non-hepatic tissues but _______ in hepatic tissues. What does this mean for the liver?
abundant, low
The liver CANNOT use ketone bodies to make energy
What is the net yield of one molecule of acetoacetate utilization?
Activation Acetoacetate to AcAcCoA costs 1 ATP
The production of 2 Acetyl Coa from AcAcCoA makes 12 ATP x2= 24 ATP
23 ATP NET
How is beta-hydroxybutarate , a _______, used to make energy?
ketone body!
beta-hydroxybutarate can be converted to acetoacetate with the release of ONE NADH that can enter the ETC. This yield 3 ATP.
Acetoactate yields 23 ATP
26 ATP NET
Which ketone body produces more energy?
B-hydroxybutarate
________ can be precursors of ketone bodies in liver. So, all factors governing _______ will affect ___________.
When fasting _________ and ________ are increased/decreased.
Fatty acid, fat mobilization, ketogenesis
fat mobilization AND ketogenesis
The liver takes up _____ % of fatty acids.
30%
An increase in acetyl CoA will do what to pyrvuate dehydrogenase?
Inhibit it to prevent modification of pyruvate to Acetyl-CoA
An increase in Acetyl CoA stimulates __________ to _______.
pyruvate carboxylase to stimulate gluconeogensis.
This will turn pyruvate into oxaloacetate to malate, eventually become glucose.
During fasting, because _______ is high _______ is enhanced.
Acetyl-CoA, gluconeogensis
When acetyl Co-A is high, ______ also form more.
ketone bodies
Why do we need ketone bodies?
During starvation, ketone bodies are the major energy fuels.
Describe how muscles use ketone bodies and FA.
At the beginning of fasting, muscles use FA and KB! For some reason, muscles stop using KB at a certain point during fasting.
How is glucose produced during fasting if needed?
Glycogen will break down to glucose
Gluconeogenesis
What is needed for gluconeogensis?
Amino acids released from protein enter the liver.
What happens when glycogen stores are used up?
ONLY gluconeogenesis can work! This means there needs to be a constant influx of AAs which can be harmful because muscle proteins can start to break down.
What is hypoglycemia? How does our body combat it?
Low glucose levels in blood because brain is using up storage of glycogen.
Ketone bodies will be used by the brain at this point.
