Fatty acid catabolism Flashcards
How lipids yield energy
Through B-oxidation of FA
How liver and heart derive energy
80% energy from FA oxidation
What is B-oxidation
A four-step enzyme catalyzed process of oxidative removal of 2-carbon units from FA to form acetyl-CoA
Why TGs are the best storage fuels
FA chains are highly reduced compounds (mainly single bonds between C and H)
-Yield twice fold energy than CHO and protein
-Insoluble in water- do not increase osmorality( are not bulky for storage)
Relatively inert- no risk of undesirable reactions (can be stored for a long time)
Where lipids are digested ( in what parts of GI)
mouth cavity
Duodenum
Stomach
Explain what happens with fats in small intestine and onward
1) Bile salts emulsify dietary fats, forming micelles
2) Intestinal lipases degrade triacylglycerols
3) FA and other break down products are taken up by the intestinal mucosa and converted into TGs
4) Tgs are incorporated, with cholesterol and apolipoproteins into chylomicrons
5) Chylomicrons move through the lymphatic system and bloodstream to tissues
6) Lipoprotein lipase, activated by apoC-II in the capillary, converts TGs to FA and glycerol-> uptake
How FA can travel in the body
In chylomicrons or NEFAs to albumin
What is going to happen to free FA
They are freely absorbed by cells. If cell need energy-> TCA cycle. Not needed-> TGs->storage
Chylomicrons travel through __ and ___, what role does portal system play in it
Travel through lymphatic system and circulatory system. Portal system helps to bring all the nutrients to the liver or to other tissues
How chilomicrons are arranged
Globular structure.
Tgs and cholesterol inside. The layer is made of apolipoproteins and phospholipids
What is the classification according to the density of lipoproteins
VLDL
ILDL(intermediate)
LDL
HDL
How proteins help in release of TGs from chylomicrons
When they are stimulated by a ligand they release TGs
Explain how lipid mobilization from storage happen
1) glucagon binds to the receptor (GPCR)->cAMP->PKA
2) PKA phosphorylates HSL(enzyme-hormone sensitive lipase) and PKA phosphorylates perilipin.This brings perilipin and HSL at the surface of the lipid droplet.
3) When perilipin is phosphorylated, CGI (comparative gene identification) dissociates ( in this case it is CGI58)
4) CGI-58 moves to ATGL (adipose TG lipase).
5) ATGL becomes active. It attacks TGs and converts it to diacylglycerol+FA
6) HSL does the conversion->monoacylglycerol+FA
7) MGL( monoacylglycerol lipase) converts monoacylglycerol->FA+glycerol
Do FAs travel free in the circulation?
No, they are bound to serum albumin
Serum albumin can carry up to ___
10 Non-esterified fatty acids (NEFA)
What happens to glycerol after TGs is broken down
1) Glycerol is phosphorylated by glycerol kinase with the use of ATP
2) Glycerol 3-phosphate is dehydrogenated by glycerol 3-phosphate dehydrogenase resulting in Dihydroxyacetonephosphate (DHAP)- glycolytic intermediate
3)DHAP is isomerized to D-glyceraldehyde 3-phosphate
Glycerol contributes only __% of the energy from TG
5
Fate of FAs when got into the cell - the first step
The first step is activation
1) Fatty acyl-Coa synthetase charges FA with ATP resulting in Fatty acyl-adenylate
2) Then Fatty acyl-adenylate can attached to the thiole group of CoA-SH and fatty acyl-CoA synthetase removes AMP resulting in Fatty acyl-CoA
The difference between synthetases and synthases
Synthetases- uses ATP
Synthases- do not use ATP
FAs activation is necessary for
transportation of FAs into mitochondria for beta-oxidation and for synthesize of longer membrane lipids
Who discovered that enzymes of FA oxidation are located in Mitochondria
Kennedy and Lehninger
How activated FAs are transported into mitochondria
Small ( less 12C) FA diffuse freely across mitochondrial membranes
-Longer FA are transported with Carnitine transport system
Explain the mechanism of carnitine transport system
1) Activated FA-CoA is attached to Carnitine by the enzyme Carnitine acyltransferase I and CoA-SH is removed on the outer membrane
2) Carnitine goes through acyl-carnitine/carnitine -passive transporter transporter in the inner membrane
3) When carnitine gets to the matrix , carnitine acyltransferse II removes carnitine and attaches CoA-SH. Now available for beta-oxidation
4 enzymes of beta-oxidation
1) acyl-CoA dehydrogenase
2) enoyl-CoA hydratase
3) Beta-hydroxyacyl-CoA dehydrogenase
4) Acyl-CoA acetyltransferase (thiolase)
Explain beta-oxidation
1) The double bond between the third and the second carbon is created counting from the carboxyl end. The function is performed by acyl-CoA dehydrogenase and use of FAD->FADH2
2) enoyl-CoA hydratase removes double bond and adds OH on the third carbon
3) Beta-hydroxy-acyl-CoA reduces NAD to NADH and thus OH and H on carbon three is turned to only double bond O(carboxyl group)
4) acyl-CoA acyltransferase (thiolase) brings ib CoA-SH and the bond between 2 and 3 carbon is broken down
Beta oxidation results in
myristoyl-CoA(Acyl-CoA)
Acetyl-CoA
Beta-oxidation of 16 FA yields
8 acetyl-CoA, 7FADH2, 7NADH,7H+->28ATP and 7H2O
How much ATP one FADH2 and NADH yield
- 5 ATP->FADH2
2. 5->NADH
How does beta-oxidation of unsaturated FA happen (If the double bond between carbon 9 and 10)
Before carbon 7 everything happens as before.
Now the double bond between carbon 3 and 4
Delta 3, delta 2-enoyl-CoA isomerase transfers the double bond to the carbon 2-3, thus skipping acyl-CoA dehydrogenase
What is the result of skipping the first step of beta-oxidation, in unsaturated fat
FADH2 is not produced->less energy
What if there is two double bonds (at carbon 9 and 10 and 12 and 13) all cis
proceeds normally until first double bond is at position 3 and 4 ( two bonds are cis)
Then Delta 3, delta 2-enoyl-CoA isomerase transfers the first bond to carbon 2 and 3 (trans at 2 and cis at 6)
One acetyl-CoA is removed
The next cycle begins
Now we have trans 2 and 3 bond and cis carbon 4 bond. This double bonds at carbon 4 does not allow beta-oxidation to continue.
2,4-dienoyl-CoA reductase comes in and removes this double bond with NADPH.
Now it is trans delta 3 and enoyl-CoA comes and finishes the reaction
What FA are more common (numbers)
Even number FA are more common; but some plants and marine organisms have odd number FA
Explain how beta-oxidation of GA with odd number carbons happen
Everything happens fine until last step. There is only 3 carbons left and it is called propionyl-CoA. It is ultimately converted to succinyl-CoA. And coenzyme B12 is important for the conversion
What enzymes create energy molecules in beta-oxidation
Enzyme 1 and 3 (FADH2 and NADH)
Beta-oxidation is regulated by both ___
Transcription factors and kinases
Where are short and long specific beta-oxidation systems situated?
Short-chain in mitochondria floating in the matrix
Very-long-chain-specific -> in the membrane
Fatty acyl-Coa synthesized in the cytoplasm is directed to
Beta-oxidation or Tg synthesis
How beta-oxidation is regulated
Malonyl-CoA, the first intermediate of FA synthesis, inhibits Carnitine Acetyltransferase I. ( if cells need more synthesize, degradation is stopped)
- Low ATP stimulates AMPK leading to activation of CArnitine shuttle
- High NADH inhibits acyl-CoA dehydrogenase
What is omega oxidation
Very rare
Only in liver and kidney in endoplasmic reticulum
FA are removed from both ends , yielding acetyl-CoA. This happens faster
Why ketone bodies are energy molecules?
Because they can be converted back to acetyl-CoA-> TCA cycle
Ketone bodies are water/lipid soluble?
Water soluble
Where ketone bodies are produced
in the liver
Three types of ketone bodies
Acetone
Acetoacetate
D-beta-hedroxybutyrate (BHB)
What is the usual concentration of acetone in the body and how it is exceted
Low concentration
Excretion-> Exhaled
Acetoacetate and BHB are involved in___ and transported to _____
Production of acetyl-coA
Transported to other tissues
Ketogenesis or ketone bodies synthesis occurs during ___ in___
During starvation or diabetes
Occurs in mitochondria within liver
What is happening in advanced stages of diabetes
A lot of ketone bodies in the liver
Acetone breathe
Ketone bodies are generated from
Extra acetyl-CoA that is present
The first step of ketogenesis
2 acetyl-CoA are converted to acetoacetyl-CoA with thiolase (last enzyme of beta-oxidation)
The second step of ketogenesis
Acetoacetyl-CoA is converted to HMG-CoA with the help of HMG-CoA synthase. This enzyme attaches third acetyl-CoA group
Where we can find HMG-CoA synthase
In mitochodria and cytoplasm
How many acetyl-CoA are sued for generation of ketone bodies
Though three are used during the cycle in the third step one is thrown out, so in total only 2 are used
What can happen to acetoacetate
It can be converted to acetone with acetoacetate decarboxylase or be converted to BDB with BDB dehydrogenase
HMG-CoA lyase can be found in
Only in mitochondria
How ketone bodies catabolism happen
Acetoacetate is attacked by beta-ketoacyl-CoA transferase and converts it to acetoacetyl-CoA.
Acetoacetyl-CoA with thiolase is converted to 2 acetyl-CoA
What is the particular with the place where you can find beta-ketoacyl-CoA transferase
It is absent in the liver. If it was present and it was functional, then ketone bodies would never leave the liver
