Flashcards in 25 - Fat Catabolism Deck (41)
What do adipocytes do when the body needs energy?
Hydrolyzes triacylglycerols (lipolysis) and releases the resulting fatty acids and glycerol
What two lipases are involved in lipolysis?
adipose triglyceride lipase (ATGL)
Hormone sensitive lipase (HSL)
What activates ATGL (adipose triglyceride lipase)?
Glucagon promotes energy mobilization
What inactivates HSL (Hormone sensitive lipase)?
Insulin inactivates it
Insulin promotes energy storage
Fatty acids are almost never found free in circulation, what protein do they bind to after hydrolysis of TG?
After hydrolysis of TG in adipocytes by lipases, where do the 3 fatty acids go and where does the glycerol go?
3 fatty acids: muscle and liver
TG is at its barest, what two ingredients?
3 fatty acids
Describe the breakdown of triacylglycerol in terms of intermediates and by products
Triacylglycerol - diacylglycerol (releases a fatty acid)
Diacylglycerol to monoacylglycerol (releases fatty acid)
monoacylglycerol to glycerol (releases fatty acid)
How does glucagon and epinephrine stimulate triacylglycerol hydrolysis?
1. They bind to a hormon-receptor on an adipocyte, causing a conformational change that activates adenylate cyclase
2. Adenylate cyclase produces cAMP from ATP
3. cAMP activates protein kinase
4. Protein kinase uses ATP to phosphorylate triacylglycerol lipase (activating it)
What deactivates triacylglycerol lipase?
A phosphatase with a Mg ion
What happens to glycerol in the liver?
The liver uses glycerol in glycolysis or gluconeogenesis, depending on its need
The liver breaks it down into L-glycerol. Then into L-glycerol-3-phosphate with glycerol kinase. Then into dihydroxy-acetone phosphate with glycerol-3-phosphate dehydrogenase
Dihydroxy-acetone phosphate is the form of glycerol that can undergo glycolysis or gluconeogenesis
What happens to fatty acids once they are in blood circulation (after being released form adipocytes)?
Fatty acids can be broken down by nearly any tissue (except brain and red blood cells)
How are fatty acids converte to acetyl-CoA, producing NADH and FADH2 on the side?
1. Fatty acids are joined to a CoA with the hydrolysis of an ATP to AMP + PPi (in the cytosol)
2. Fatty acyl-CoA is then transported into the mitochondrial matrix where it is oxidized to acetyl-CoA, one NAD+ and one FAD are reduced in the process to NADH and FADH2
Where are fatty acids oxidized?
In the mitochondria
Which carbons are removed with each cycle of fatty acid oxidation?
Each reaction cycle removes 2 carbon atoms from beginning of the chain with the carboxy group
How is fatty acid oxidation regulated?
Through transport of fatty acids into mitochondria
Energy production from fatty acids requires what element?
What is step 1 of fatty acid oxidation? (β-oxidation)? Where do the products end up? (begins in cytosol)
Fatty acids are activated in the cytosol by the conjugation to coenzyme A (CoA)
This step costs 1 ATP and Acyl-CoA synthetase is the enzyme used (embedded into outer membrane of mitochondria). Acyl-CoA is in intermembrane space of mitochondria at this point.
What is step 2 of fatty acid oxidation? (begins in cytosol/intermembrane space of mitochondria)
Transport into the mitochondrial matrix
Carnitine acyltransferase converts a carnitine into acylcarnitine, releasing CoA as CoASH into the intermembrane space.
Acylcarnitine (fatty acid + carnitine) is then carried by a protein into the mitochondrial matrix.
In the mitochondrial matrix acyl-carnitine is broken down into carnitine and acyl-CoA (with the addition of CoASH). Acyl-CoA is then in the mitochondrial matrix and ready for breakdown.
What is step 3 of fatty acid oxidation? (begins in mitochondrial matrix)
1. In the mitochondrial matrix acyl-CoA is broken down by acyl-CoA dehydrogenase to form trans-α, β-enoyl-CoA, reducing an FAD to a FADH2 in the process.
2. Trans-α, β-enoyl-CoA is then converted by anoyl-CoA hydrolase to form L-β-hydroxyacyl-CoA, using an H2O
3. See summary below...
In other terms,
1. There is formation of double bond between alpha and beta carbon of the fatty acid chain by acyl-CoA dehydrogenase. Formation of FADH2
2. Hydration of the double bond, forming a hydroxyl group on the beta carbon.
3. Dehydrogenation by 3-L-hydroxyacyl-CoA dehydrogenase forming a ketogroup at the beta carbon and NADH
4. Carbon-carbon cleavage between the α and β-carbon by β-keoacyl-CoA thiolase, shortening the chain by 2 carbons and forming acetyl CoA. Fatty acid chain is degraded from carboxy side, nor from the end.
What is the total amount of ATP made from the full oxidation of palmitate? (C16:0)
6.6 ATP per carbon
How many rounds of oxidation can a 16 carbon fatty acid with no double bonds (palmitate) undergo? How much NAD+, FAD, CoASH and H2O is needed?
7 rounds of β-oxidation.
2 ATP is needed for activation with CoA
Without the presence of oxygen, what provides greater energy yields, oxidation of fatty acids or oxidation of glucose? With oxygen? Why?
Oxidation of fatty acids, because fatty acids are more reduced.
However, glucose can make some ATP without oxygen in the cytosol, where fatty acids cannot generate any ATP without oxygen. Therefore, per oxygen more ATP is made form glucose.
Describe the oxidation of very long chain fatty acids
Oxidation in peroxisomes to medium-chain fatty acids, which are then oxidized in the mitochondria. Peroxisomal fatty acid oxidation does not yield ATP.
Describe oxidation of unsaturated fatty acids
Additional enzymes are required to degrade the carbon around double bonds. Odd-numbered double bonds requires an isomerase, even-numbered bonds require a dehydrogenase. Energy yield is lower than from saturated fatty acids.
Describe the oxidation of odd chain fatty acids
Oxidation yields propionic acid, which is converted to succinyl CoA. This is the only way that part of a fatty acid can be glucogenic (intermediate in TCA cycle)
Describe the oxidation of branched chain fatty acids
Occur in dairy products and products derived from herbivores. Branch points in the carbon chain prevents β-oxidation. Branched chain fatty acids are broken down by α-oxidation
How does vitamin B12 deficiency cause neurological damage?
Because of the accumulation of odd-chain fatty acids in the neuronal membranes.
Vitamin B12 plays a part in odd-chain fatty acid oxidation to make succinyl-CoA
Describe the steps in the αoxidation of phytanic acid (a branched chain fatty acid) to pristanic acid. What happens to this pristanic acid?
1. Phytanic acid is converted to phytanoyl-CoA
2. Oxidation by hydroxylase using oxygen
3. Decarboxylation requires TPP cofactor, pristanic acid is made
Pristanic acid is then added to CoA with acyl-CoA synthetase, which goes through 6 cycles of β-oxidation.
What results is: