Lecture 31: Lipid Catabolism Flashcards
Refresher on Lipids
What are the types of lipids?
Simple (Fat, Oil, Wax)
Complex (Phospholipids, glycolipids)
Sterol (Cholesterol, others)
Refresher on Lipids
Which of the lipids are triacylglycerols?
Focus of this section
Fat and oil (fatty acids)
Catabolism of Lipids
What are triacylglycerols split into?
Glycerol and fatty acids
Lipid Importance
Why are lipids important to cells?
Fuel
* 1/3 of out energy comes from dietary triacylglycerols
* 80% energy needs of mammalian heart and liver are met by oxidation of fatty acids
* many hibernating animals rely on stored fats for energy
Building blocks
* phospholipids
* glycolipids
Precursors of hormones and messengers
Used to target proteins to membrane sites
Triacylglycerol as energy storage
What is one advantage of fats over polysaccharides?
They are highly reduced
-carry more energy per carbon
Triacylglycerol as energy storage
What is a second advantage of fats over polysaccharides?
Anhydrous
-carry less water since they are nonpolar
-can carry more than 6x the energy per gram than a gram of glycogen
Triacylglycerol as energy storage
What type of energy storage are these?
Long term, slow delivery
(vs short term, quick energy of glucose and glycogen)
Triacylglycerol as energy storage
Where is the main storage?
adipose tissue
Digestion and Transportation
Where do triacylglycerols form Lipid Droplets?
of Fats
stomach
Digestion and Transportation
What is secreted by the gall bladder and how does it help digestion?
of fats
Bile acids, as bile salts
renders the droplets more accesible to digestion by lipases
Digestion and Transportation
What is a lipase?
Secreted by the pancreas, digests the triacylglycerols into 2 fatty acids and monoacylglycerol
Digestion and Transportation
How and where are digestion products carried?
as micelles to the intestinal epithelium cells to be absorbed
Digestion and Transportation
What happens to triacylglycerols in the intestine?
reform from free fatty acids and monoacyglycerol
packaged into lipoproteins particles called chylomicrons
Digestion and Transportation
Where do the chylomircons take the triacylglycerols?
from the intestine to the blood
Breakdown of Triacyglycerols
What are some lipase regulated by?
The hormones glucagon and epinephrine
Breakdown of Triacyglycerols
What are the glycerols absorbed by and converted to?
Liver
Glycolytic intermediates (for glycolysis or glyconeogenesis)
Breakdown of Triacyglycerols
What are the fatty acids absorbed by and converted to?
transported to other tissues for fuel
Glycerol
What activates glycerol and what is it at the expense of?
Glycerol Kinase
ATP
Glycerol
Why is it ok that this reaction uses ATP?
Later reactions recover more ATP than what this uses, so it covers the cost
Fatty Acid Transport
Where are they transported into for b-oxidation?
The mitochondria, from the cytosol
Fatty Acid Transport
Can fatty acids difuse across the mitochondrial membrane freely?
Only if they are under 12 carbons, those over have to be activated into fatty acyl-CoA for transport
Fatty Acid Transport
What enam catalyzes the reaction to allow these larger fatty acids across?
Acyl CoA synthetase on the mitochondrial membrane
Fatty acid Transport
What actually transports these larger fatty acids?
Carnitine
b-Oxidation of Fatty acyl-CoA
What does this generally consist of?
oxidative conversion of 2C units into acetyl CoA (shorted by 2C each round) with concomitant generation of NADH and FADH2
b-Oxidation of Fatty acyl-CoA
What does each round of degradation involve?
- Oxidation of acyl-CoA, catalyzed by acyl CoA dehydrongenase to generate trans-delta2-enoyl CoA and FADH2
- Hydration of trans-delta2-enoyl CoA by enoyl CoA hydratase to generate L-3-hydroxyacyl CoA
- Oxidation of L-3-hydroxyacyl CoA by L-3-hydroxyacyl CoA dehydrogenase to generate 3-ketoacyl CoA and NADH
- Cleavage of the 3-ketoacyle CoA by thiolase forms acetyl CoA and a fatty acid chain (acyl CoA) that is 2 carbons shorter (thiolysis)
Complete Oxidation of Fatty Acids
What is stage 1?
Oxidative conversion of 2C units into acetyl-CoA via b-oxidation with concomitant generation of NADH and FADH2
Complete Oxidation of Fatty Acids
What is the general reaction of Stage 1?
Cn-acyl CoA + FAD + NAD + H2O + CoA
–>
Cn-2-acyl CoA + FADH2 + NADH + acetyl CoA + H
Complete Oxidation of Fatty Acids
What is stage 2?
oxidation of acetyl-CoA into CO2 via CAC with concomitant generation of NADH and DAFH2
Complete Oxidation of Fatty Acids
What is the general reaction of stage 2?
Acetyl-CoA + 3 NAD + FAD + GDP + Pi + 2 H2O
–>
2 CO2 + 3NADH + FADH2 + GTP + CoA +3 H
Complete Oxidation of Fatty Acids
How many ATP does acetyl-CoA produce overall?
10
(3 NADH = 7.5 ATP
1 FADH2 = 1.5 ATP
1 GTP = 1 ATP)
Complete Oxidation of Fatty Acids
What is stage 3?
generation of ATP from stage 1’s NADH and FADH2 via the respiratory chain
Complete Oxidation of Fatty Acids
What is stage 3’s ATP generation?
FADH2 = 1.5 ATP
NADH = 2.5 ATP
Complete Oxidation of Fatty Acids
How many ATP does a C16 acyl-CoA with 7 rounds of b-oxidation produce?
8 acetyl-Coa = 10 x 8=80
7 FADH2 = 1.5 x 7 = 10.5
7 NADH = 2.5 x 7 = 17.5
Activation = -2
Total: 106 ATP
Complete Oxidation of Fatty Acids
Q from Lecture: How about the b-oxidation of myristyl-CoA (C14:0)?
How many ATP is generated
6 rounds of b-oxidation
70+9+15-2
92 ATP
Oxidation of Unsaturated Fatty Acids
What do unsaturated fatty acids contain?
cis double bonds
Oxidation of Unsaturated Fatty Acids
What is required to oxidize unsaturated fatty acids?
2 additional enams:
* Isomerase (converts the cis double bond to trans at C3)
* reductase (reduces cis doubles bonds not at C3)
Oxidation of Unsaturated Fatty Acids
Which unsaturated FA require these enams?
isomerase and reductase
Monounsaturated: require isomerase
Polyunsaturated: requires both
Oxidation of Unsaturated Fatty Acids
Why do unsaturated FA need extra enams?
Because the cis double bonds mean that they are not able to be a substrate from enoyl-CoA hydratase
Oxidation of Odd-numbered FA
What forms from oxidation of odd numbered FA?
Propionyl-CoA Carboxylase
Oxidation of Odd-numbered FA
What is Propionyl-CoA Carboxylase?
a biotin enzyme, it adds a carbon to propionyl CoA to form methylmalonyl CoA (so that it can go through b-oxidation)
Oxidation of Odd-numbered FA
Do odd-numbered FA use b-oxidation?
yes, but b-oxidation cannot process 3C units, so they have to be converted into an even number form
Oxidation of Odd-numbered FA
What is formed from Methylmalonyl CoA?
Succinyl CoA (CAC component) using methylmalonyl CoA Mutase which requires vitamin B12
Formation of Ketone Bodies
Can fatty acids be used to synthesize glucose?
No, since acetyl-CoA cannot synthesize oxaloacetate
Formation of Ketone Bodies
What happens when the level of oxaloacetate decreases?
Due to diabetes or starvation
The CAC slows down and Acetyl-CoA cannot be brought into the CAC. Instead it is converted into ketone bodies
Formation of Ketone Bodies
What ketone bodies does Acetyl-CoA form?
Acetoacetate, D-3-hydroxybutyrate, and acetone
Formation of Ketone Bodies
What can excess production of ketone bodies lead to?
Acidosis (decreases pH of the blood, can threaten the persons life)
