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Questions and Answers
What is the primary source of energy for hibernating animals?
What is the primary source of energy for hibernating animals?
What is the role of carnitine in fatty acid metabolism?
What is the role of carnitine in fatty acid metabolism?
How much net ATP is generated from the complete oxidation of palmitic acid?
How much net ATP is generated from the complete oxidation of palmitic acid?
What initiates the hydrolysis of triglycerides in adipose tissue?
What initiates the hydrolysis of triglycerides in adipose tissue?
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In β-oxidation, how many rounds are needed to completely oxidize a saturated fatty acid with 16 carbons?
In β-oxidation, how many rounds are needed to completely oxidize a saturated fatty acid with 16 carbons?
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What is the primary energy outcome of one molecule of NADH during cellular respiration?
What is the primary energy outcome of one molecule of NADH during cellular respiration?
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Which enzyme is necessary for the isomerization of an intermediate with a double bond between C-3 and C-4 during beta-oxidation of monounsaturated fatty acids?
Which enzyme is necessary for the isomerization of an intermediate with a double bond between C-3 and C-4 during beta-oxidation of monounsaturated fatty acids?
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Which of the following statements is true regarding the energy yield of polyunsaturated fatty acid oxidation compared to saturated fatty acids?
Which of the following statements is true regarding the energy yield of polyunsaturated fatty acid oxidation compared to saturated fatty acids?
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What is the end product of odd-numbered fatty acid oxidation?
What is the end product of odd-numbered fatty acid oxidation?
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What is the role of coenzyme B12 in the oxidation of odd-number fatty acids?
What is the role of coenzyme B12 in the oxidation of odd-number fatty acids?
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What is the role of malonyl-CoA in fatty acid synthesis?
What is the role of malonyl-CoA in fatty acid synthesis?
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Which of the following statements about ketone bodies is true?
Which of the following statements about ketone bodies is true?
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What is the function of hydroxocobalamin as approved by the FDA?
What is the function of hydroxocobalamin as approved by the FDA?
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Which tissues can utilize ketone bodies when glucose is not available?
Which tissues can utilize ketone bodies when glucose is not available?
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What inhibits beta-oxidation during high glucose levels?
What inhibits beta-oxidation during high glucose levels?
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Study Notes
Fatty Acid Catabolism
- Fats are esters of glycerol and fatty acids.
- Fats are highly reduced structures, similar to hydrocarbons, providing high energy.
- In liver and heart, fats provide ~80% of the total energy consumed.
- Fats are hydrophobic and inert, segregating from water; thus, easy to store as lipid droplets without raising osmolarity.
- Fats can be stored in large amounts in cells without risk of undesired chemical reactions.
- Fats are the sole source of energy for hibernating animals and migratory birds.
Digestion, Mobilization, and Transport of Fats
- Bile salts emulsify dietary fats, forming mixed micelles.
- Intestinal lipases degrade triacylglycerols.
- Fatty acids and other breakdown products are taken up by the intestinal mucosa.
- These are converted to triacylglycerols, packaged with cholesterol and apolipoproteins into chylomicrons.
- Chylomicrons are transported through the lymphatic system and bloodstream to tissues.
- Lipoprotein lipase converts triacylglycerols into fatty acids and glycerol in capillaries.
- Fatty acids enter cells.
Structure of Chylomicrons
- Size: 100-500 nm.
- Composition:
- Triacylglycerols (80%)
- Phospholipids
- Cholesterol
- Cholesterol esters
- Apolipoproteins (lipid-binding proteins)
- Various lipid and protein combinations are distinguished (chylomicrons, VLDL, VHDL)
Mobilization of Triacylglycerols Stored in Adipose Tissue
- Binding of epinephrine stimulates adenylyl cyclase.
- cAMP activates protein kinase A (PKA).
- PKA phosphorylates perilipin on the surface of lipid droplets, making fats accessible to hormone-sensitive lipase (HSL).
- HSL hydrolyzes triacylglycerides into fatty acids and glycerol.
- Fatty acids leave adipocytes and are transported by serum proteins like albumin to muscles for energy generation.
Metabolism of Glycerol
- Glycerol accounts for ~5% of total energy from fats.
- Energy is harvested through conversion into glyceraldehyde 3-phosphate and then through the normal glycolytic pathway.
- All phosphorylated species are negatively charged and trapped in the cytoplasm.
Fatty Acid "Activation" Prior to Oxidation
- Enzymes for fatty acid oxidation are located in the mitochondrial matrix.
- Fatty acids are conjugated with CoA before oxidation.
- Conjugation is highly exothermic, releasing pyrophosphate.
- Pyrophosphate is hydrolyzed into two phosphate molecules.
Fatty Acid Transport into Mitochondria
- Carnitine acts as a fatty acid shuttle between cytosol and the mitochondrial interior.
- Fatty acids are converted into carnitine esters, committing the fatty acids to mitochondrial oxidation.
Oxidation of Fatty Acids
- Fatty acid oxidation occurs primarily in the mitochondria.
- Three stages:
- Sequential β-oxidation rounds to generate acetyl-CoA.
- Oxidation of acetyl-CoA to CO2, FADH2, and NADH using the citric acid cycle.
- Transfer of electrons from FADH2 and NADH to O2 to generate ATP via the respiratory chain.
Stage 1: β-Oxidation of Saturated Fatty Acids
- Acyl-CoA dehydrogenase catalyzes the first step.
- Enoyl-CoA hydratase catalyzes the hydration step.
- β-hydroxyacyl-CoA dehydrogenase catalyzes the oxidation step.
- β-ketoacyl-CoA thiolase catalyzes the cleavage step.
β-Oxidation of Saturated Fatty Acids: Energy Balance
- Complete energy yield from palmitic acid (C16) to acetyl-CoA.
- Rounds of β-oxidation: (n/2) - 1 where n = number of carbons.
- 7 NADH, 7 FADH2 from oxidation, 8 Acetyl CoA generated provides total net ATP of 129.
Monounsaturated Fatty Acid Oxidation
- Additional isomerase step required to convert cis to trans.
Polyunsaturated Fatty Acid Oxidation
- Additional enzymes (2,4-dienoyl-CoA reductase, and enoyl-CoA isomerase) required.
- Less energy generated due to reduced NADPH production.
Mono/polyunsaturated Fatty Acid Oxidation: Summary
- Most naturally occurring unsaturated fatty acids have the cis conformation.
- This causes problems for β-oxidation.
- Intermediate with a double bond between C3 and C4 (normally C2 and C3) is produced. Need isomerase.
- Cis double bond between C4 and C5 yields a trans-2-cis-4 intermediate. Need Reductase to decrease the 2,4 double bond and isomerase to produce the normal β-oxidation substrate.
- Two additional enzymes are needed.
- Less energy produced compared to saturated fatty acids.
Oxidation of Odd-Number Fatty Acids
- Odd-number fatty acids yield propionyl-CoA at the end of β-oxidation.
- Propionyl-CoA is converted into succinyl-CoA for use in the citric acid cycle.
- Coenzyme B12 catalyzes a key isomerization.
Regulation of Fatty Acid Oxidation
- High glucose levels stimulate the enzyme that synthesizes the fatty acid precursor, malonyl-CoA.
- Malonyl-CoA inhibits beta-oxidation.
Ketone Bodies – Alternative Fuel to Sugars
- Acetyl-CoA from fatty acid oxidation can be converted into ketone bodies.
- Ketone bodies (acetoacetate, acetone, and β-hydroxybutyrate) are alternative fuels for tissues when glucose is unavailable.
- Accumulation of ketone bodies leads to ketoacidosis.
Ketone Bodies – Use of Ketone Bodies for Energy
- Ketone bodies (β-hydroxybutyrate, acetoacetate) are converted to acetyl-CoA in peripheral tissues to generate energy.
- The enzyme β-ketoacyl-CoA transferase is needed to convert ketone bodies into acetyl CoA in peripheral tissues but is not in the liver.
Ketone Bodies Formation and Export from the Liver
- Starvation and untreated diabetes lead to overproduction of ketone bodies due to high activity of fatty acid oxidation.
- Acetoacetate and D-β-hydroxybutyrate are exported as energy sources to tissues that can't use glucose.
Ketone Bodies – Summary
- Liver acetyl-CoA from β-oxidation can go through two paths.
- Enter the TCA cycle
- Form ketone bodies
Drugs and Diseases
- Diseases: diabetes, diabetic ketoacidosis (metabolic acidosis).
- Drugs and vitamins: epinephrine (adrenaline), vitamin B12, hydroxocobalamin.
- Metabolites and blood components: chylomicrons, VLDL, LDL, HDL, ketone bodies.
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Description
Explore the intricate process of fatty acid catabolism and the digestion, mobilization, and transport of fats. This quiz covers essential concepts such as energy production from fats, emulsification by bile salts, and the formation of chylomicrons. Test your understanding of how fats are processed in the body and their significance in energy metabolism.
