Podcast
Questions and Answers
What hormonal state favors the synthesis of long-chain, even-numbered saturated fatty acids?
What hormonal state favors the synthesis of long-chain, even-numbered saturated fatty acids?
- High insulin/glucagon ratio (correct)
- High epinephrine/glucagon ratio
- Low insulin/glucagon ratio
- Low cortisol/adrenaline ratio
Which carrier is involved in transporting acyl/acetyl groups between mitochondria and cytosol during the synthesis of long-chain, even-numbered saturated fatty acids?
Which carrier is involved in transporting acyl/acetyl groups between mitochondria and cytosol during the synthesis of long-chain, even-numbered saturated fatty acids?
- Carnitine
- Coenzyme A
- Acyl carrier protein
- Citrate (correct)
Which coenzyme is used for oxidation/reduction reactions in the synthesis of long-chain, even-numbered saturated fatty acids?
Which coenzyme is used for oxidation/reduction reactions in the synthesis of long-chain, even-numbered saturated fatty acids?
- FADH2
- NADPH (correct)
- Coenzyme Q
- NADP+
What subcellular location is primarily associated with the degradation of long-chain, even-numbered saturated fatty acids?
What subcellular location is primarily associated with the degradation of long-chain, even-numbered saturated fatty acids?
During the synthesis of long-chain, even-numbered saturated fatty acids, what is the two-carbon donor/product?
During the synthesis of long-chain, even-numbered saturated fatty acids, what is the two-carbon donor/product?
Which compound inhibits the synthesis of long-chain, even-numbered saturated fatty acids?
Which compound inhibits the synthesis of long-chain, even-numbered saturated fatty acids?
Which molecule provides the highest amount of ATP during the oxidation of palmitoyl CoA?
Which molecule provides the highest amount of ATP during the oxidation of palmitoyl CoA?
Which metabolic disorder is characterized by the inability to oxidize medium-chain fatty acids leading to hypoglycemia?
Which metabolic disorder is characterized by the inability to oxidize medium-chain fatty acids leading to hypoglycemia?
How many ATP are produced from the oxidation of 7 NADH molecules during the breakdown of palmitoyl CoA?
How many ATP are produced from the oxidation of 7 NADH molecules during the breakdown of palmitoyl CoA?
What is the total energy yield from the oxidation of palmitoyl CoA after accounting for the activation energy?
What is the total energy yield from the oxidation of palmitoyl CoA after accounting for the activation energy?
What key intermediate is produced during the breakdown of fatty acids with an odd number of carbons?
What key intermediate is produced during the breakdown of fatty acids with an odd number of carbons?
What leads to a significant decrease in glucose levels in patients with MCAD deficiency?
What leads to a significant decrease in glucose levels in patients with MCAD deficiency?
Which enzyme deficiency is particularly linked to sudden infant death syndrome (SIDS)?
Which enzyme deficiency is particularly linked to sudden infant death syndrome (SIDS)?
In the context of beta oxidation of palmitoyl CoA, what is the significance of electron transport chain in yielding ATP?
In the context of beta oxidation of palmitoyl CoA, what is the significance of electron transport chain in yielding ATP?
Which enzyme catalyzes the transfer of the acyl group from CoA to carnitine?
Which enzyme catalyzes the transfer of the acyl group from CoA to carnitine?
What compound inhibits the entry of long-chain acyl groups into the mitochondrial matrix?
What compound inhibits the entry of long-chain acyl groups into the mitochondrial matrix?
Which tissue contains about 97% of all carnitine in the body?
Which tissue contains about 97% of all carnitine in the body?
From which amino acids can carnitine be synthesized?
From which amino acids can carnitine be synthesized?
Which enzyme catalyzes the transfer of the acyl group from carnitine to CoA in the mitochondrial matrix?
Which enzyme catalyzes the transfer of the acyl group from carnitine to CoA in the mitochondrial matrix?
What is the role of carnitine-acylcarnitine translocase?
What is the role of carnitine-acylcarnitine translocase?
In which tissues can carnitine synthesis occur?
In which tissues can carnitine synthesis occur?
Which factor decreases the CoA-requiring thiolase reaction during fatty acid oxidation?
Which factor decreases the CoA-requiring thiolase reaction during fatty acid oxidation?
What is a primary characteristic of secondary carnitine deficiency?
What is a primary characteristic of secondary carnitine deficiency?
Which condition is related to primary carnitine deficiency?
Which condition is related to primary carnitine deficiency?
How does genetic CPT-I deficiency primarily affect the body?
How does genetic CPT-I deficiency primarily affect the body?
Which of the following is true about medium-chain fatty acids?
Which of the following is true about medium-chain fatty acids?
What molecule is directly produced during the first oxidation step in beta-oxidation?
What molecule is directly produced during the first oxidation step in beta-oxidation?
What is the net ATP yield from the complete oxidation of a palmitate molecule?
What is the net ATP yield from the complete oxidation of a palmitate molecule?
Which step in beta-oxidation involves a thiolytic cleavage?
Which step in beta-oxidation involves a thiolytic cleavage?
What metabolic complication is NOT associated with CPT-II deficiency?
What metabolic complication is NOT associated with CPT-II deficiency?
What role does acetyl CoA play in linking fatty acid oxidation to gluconeogenesis?
What role does acetyl CoA play in linking fatty acid oxidation to gluconeogenesis?
What dietary modification is recommended for someone with carnitine deficiency?
What dietary modification is recommended for someone with carnitine deficiency?
Which enzyme is specifically required for the oxidation of monounsaturated fatty acids like 18:1(9) (oleic acid)?
Which enzyme is specifically required for the oxidation of monounsaturated fatty acids like 18:1(9) (oleic acid)?
What is a product of the initial dehydrogenation in peroxisomes during the oxidation of very-long-chain fatty acids?
What is a product of the initial dehydrogenation in peroxisomes during the oxidation of very-long-chain fatty acids?
What is the side product formed when FADH2 is oxidized by molecular oxygen in the peroxisome?
What is the side product formed when FADH2 is oxidized by molecular oxygen in the peroxisome?
Which disorder results from the inability to transport very-long-chain fatty acids across the peroxisomal membrane?
Which disorder results from the inability to transport very-long-chain fatty acids across the peroxisomal membrane?
What is the enzyme responsible for hydroxylating the α-carbon of phytanic acid in α-oxidation?
What is the enzyme responsible for hydroxylating the α-carbon of phytanic acid in α-oxidation?
What compound is produced when the initial carbon is released as CO2 during the α-oxidation of phytanic acid?
What compound is produced when the initial carbon is released as CO2 during the α-oxidation of phytanic acid?
Which enzyme deficiency causes Refsum disease?
Which enzyme deficiency causes Refsum disease?
Liver mitochondria can convert acetyl CoA into which functional ketone bodies?
Liver mitochondria can convert acetyl CoA into which functional ketone bodies?
What happens to the energy output when oxidizing unsaturated fatty acids compared to saturated fatty acids?
What happens to the energy output when oxidizing unsaturated fatty acids compared to saturated fatty acids?
Which enzyme is required for the oxidation of polyunsaturated fatty acids such as 18:2(9,12) (linoleic acid) in addition to the isomerase?
Which enzyme is required for the oxidation of polyunsaturated fatty acids such as 18:2(9,12) (linoleic acid) in addition to the isomerase?
What activates Acetyl CoA carboxylase during fatty acid synthesis?
What activates Acetyl CoA carboxylase during fatty acid synthesis?
Which component is NOT involved in fatty acid synthesis in the liver?
Which component is NOT involved in fatty acid synthesis in the liver?
What compound inhibits carnitine palmitoyltransferase I, preventing fatty acid degradation in mitochondria?
What compound inhibits carnitine palmitoyltransferase I, preventing fatty acid degradation in mitochondria?
Where does the oxidation of very-long-chain fatty acids (VLCFA) primarily occur?
Where does the oxidation of very-long-chain fatty acids (VLCFA) primarily occur?
Which enzyme deficiency leads to a common inborn error of metabolism causing hypoketonemia and hypoglycemia?
Which enzyme deficiency leads to a common inborn error of metabolism causing hypoketonemia and hypoglycemia?
What role does the glycerol backbone from degraded triacylglycerol play in the liver?
What role does the glycerol backbone from degraded triacylglycerol play in the liver?
What enzyme is necessary for β-oxidation of fatty acids with an odd number of carbons to convert methylmalonyl CoA to succinyl CoA?
What enzyme is necessary for β-oxidation of fatty acids with an odd number of carbons to convert methylmalonyl CoA to succinyl CoA?
Which compound is an allosteric activator of Acetyl CoA carboxylase?
Which compound is an allosteric activator of Acetyl CoA carboxylase?
In what cellular location does fatty acid desaturation occur?
In what cellular location does fatty acid desaturation occur?
What is the primary regulator of the enzyme hormone-sensitive lipase in adipose tissue?
What is the primary regulator of the enzyme hormone-sensitive lipase in adipose tissue?
Why are fatty acids considered important sources of energy for peripheral tissues?
Why are fatty acids considered important sources of energy for peripheral tissues?
What leads to the production of fatty acids in the liver?
What leads to the production of fatty acids in the liver?
Which enzyme's inhibition and activation are influenced by elevated hepatic acetyl CoA?
Which enzyme's inhibition and activation are influenced by elevated hepatic acetyl CoA?
What allows for the continued oxidation of fatty acids during ketogenesis?
What allows for the continued oxidation of fatty acids during ketogenesis?
What determines the equilibrium between acetoacetate and 3-hydroxybutyrate?
What determines the equilibrium between acetoacetate and 3-hydroxybutyrate?
Which enzyme is the rate-limiting step in the synthesis of ketone bodies?
Which enzyme is the rate-limiting step in the synthesis of ketone bodies?
Where is HMG CoA synthase primarily active?
Where is HMG CoA synthase primarily active?
What can acetoacetate spontaneously decarboxylate into?
What can acetoacetate spontaneously decarboxylate into?
What happens to the NAD+/NADH ratio during fatty acid oxidation?
What happens to the NAD+/NADH ratio during fatty acid oxidation?
In the context of fatty acid oxidation disorders, what are the typical metabolic presentations?
In the context of fatty acid oxidation disorders, what are the typical metabolic presentations?
Which ketone body is produced through the reduction of acetoacetate?
Which ketone body is produced through the reduction of acetoacetate?
What is the initial substrate for ketone body synthesis in the liver?
What is the initial substrate for ketone body synthesis in the liver?
Which enzyme reduces acetoacetate to 3-hydroxybutyrate?
Which enzyme reduces acetoacetate to 3-hydroxybutyrate?
What condition results from the excessive accumulation of ketone bodies in the blood?
What condition results from the excessive accumulation of ketone bodies in the blood?
Which of the following molecules is NOT a ketone body?
Which of the following molecules is NOT a ketone body?
What enzyme is responsible for converting acetoacetate to acetone?
What enzyme is responsible for converting acetoacetate to acetone?
What initiates the synthesis of triacylglycerol in response to excess calorie intake?
What initiates the synthesis of triacylglycerol in response to excess calorie intake?
What symptom is NOT typically associated with ketoacidosis?
What symptom is NOT typically associated with ketoacidosis?
Which enzyme activity is associated with triacylglycerol degradation in a calorie-deficient diet?
Which enzyme activity is associated with triacylglycerol degradation in a calorie-deficient diet?
Which enzyme transfers CoA from succinyl CoA to acetoacetate?
Which enzyme transfers CoA from succinyl CoA to acetoacetate?
What is the role of Malonyl CoA in the liver cytosol?
What is the role of Malonyl CoA in the liver cytosol?
Which of the following is NOT a product of HMG-CoA breakdown?
Which of the following is NOT a product of HMG-CoA breakdown?
What happens to fatty acids in most tissues?
What happens to fatty acids in most tissues?
In diabetes mellitus, what primarily triggers the increased production of ketone bodies?
In diabetes mellitus, what primarily triggers the increased production of ketone bodies?
What process occurs in the liver as a result of fatty acid breakdown?
What process occurs in the liver as a result of fatty acid breakdown?
Which hormone stimulates triacylglycerol synthesis?
Which hormone stimulates triacylglycerol synthesis?
In patients with medium-chain fatty acyl CoA dehydrogenase (MCAD) deficiency, why does fasting hypoglycemia occur?
In patients with medium-chain fatty acyl CoA dehydrogenase (MCAD) deficiency, why does fasting hypoglycemia occur?
What is the specific defect in Zellweger syndrome that causes an accumulation of both very long chain fatty acids (VLCFA) and phytanic acid?
What is the specific defect in Zellweger syndrome that causes an accumulation of both very long chain fatty acids (VLCFA) and phytanic acid?
Which compound is expected to be radioactively labeled when industrial workers breathe air contaminated with ¹⁴C-labeled carbon dioxide?
Which compound is expected to be radioactively labeled when industrial workers breathe air contaminated with ¹⁴C-labeled carbon dioxide?
A teenager on a fat-free diet would be deficient in the synthesis of which lipid?
A teenager on a fat-free diet would be deficient in the synthesis of which lipid?
Which of the following accurately depicts the defect in X-linked adrenoleukodystrophy (X-ALD)?
Which of the following accurately depicts the defect in X-linked adrenoleukodystrophy (X-ALD)?
What is a common metabolic feature of Zellweger syndrome?
What is a common metabolic feature of Zellweger syndrome?
Why are ketone bodies not found in the urine of patients with medium-chain fatty acyl CoA dehydrogenase (MCAD) deficiency during hypoglycemia?
Why are ketone bodies not found in the urine of patients with medium-chain fatty acyl CoA dehydrogenase (MCAD) deficiency during hypoglycemia?
Why does a defect in fatty acid transport into peroxisomes result in the accumulation of very long chain fatty acids (VLCFA) in X-ALD?
Why does a defect in fatty acid transport into peroxisomes result in the accumulation of very long chain fatty acids (VLCFA) in X-ALD?
Study Notes
Synthesis and Degradation of Fatty Acids
- Synthesis of Fatty Acids:
- Occurs in the liver
- Greatest flux through pathway: after a carbohydrate-rich meal
- Hormonal state favoring pathway: high insulin/glucagon ratio
- Major tissue site: liver
- Subcellular location: cytosol
- Carriers of acyl/acetyl groups between mitochondria and cytosol: citrate
- Phosphopantetheine-containing active carriers: acyl carrier protein domain, coenzyme A
- Oxidation/reduction coenzymes: NADPH
- Two-carbon donor/product: malonyl CoA
- Activator: citrate
- Inhibitor: long-chain fatty acyl CoA
- Product of pathway: palmitate
Oxidation of Fatty Acids
- Beta Oxidation:
- Process yields 129 ATP total
- Produces 7 FADH2 molecules, each providing 2 ATP when oxidized by CoQ of the electron transport chain, for a total of 14 ATP
- Produces 7 NADH molecules, each providing 2 ATP when oxidized by NADH dehydrogenase, for a total of 21 ATP
- Remaining 7 acetyl CoA molecules provide 12 ATP each when converted to CO2 and H2O by the TCA cycle, for a total of 96 ATP
- Process requires 2 ATP to activate the palmitate to palmitoyl CoA, subtracted from the total
- Medium-Chain Fatty Acyl CoA Dehydrogenase (MCAD) Deficiency:
- A metabolic disorder caused by a deficiency in the MCAD enzyme
- Occurs in 1:14,000 births worldwide
- Causes a decrease in the ability to oxidize fatty acids with 6-10 carbons
- Results in hypoglycemia and a build-up of fatty acids in the urine and blood
- Treatment includes avoidance of fasting
Oxidation of Unsaturated Fatty Acids
- Unsaturated Fatty Acid Oxidation:
- Provides less energy than saturated fatty acid oxidation
- Requires an additional enzyme, 3,2-enoyl CoA isomerase, for monounsaturated fatty acids
- Requires an NADPH-dependent 2,4-dienoyl CoA reductase for polyunsaturated fatty acids
Ketone Bodies: An Alternate Fuel for Cells
- Ketone Body Synthesis:
- Occurs in the liver
- Ketone bodies are produced from acetyl CoA derived from fatty acid oxidation
- Compounds categorized as ketone bodies: acetoacetate, 3-hydroxybutyrate, and acetone
- Acetoacetate can be reduced to form 3-hydroxybutyrate or decarboxylate to form acetone
- Ketone Body Use by Peripheral Tissues:
- Ketone bodies are used as an alternate fuel for cells
- Produced in the liver and transported to peripheral tissues
- Can be used by the brain to spare glucose during prolonged fasting
Disorders of Fatty Acid Oxidation
- Disorders of Fatty Acid Oxidation:
- Present with hypoketosis and hypoglycemia
- Caused by defects in fatty acid oxidation or transport
- Symptoms include muscle weakness, hypoglycemia, and sudden infant death syndrome (SIDS)
Excessive Production of Ketone Bodies in Diabetes Mellitus
- Diabetic Ketoacidosis:
- Caused by a lack of insulin
- Leads to increased lipolysis and production of ketone bodies
- Symptoms include fruity breath odor, rapid breathing, nausea, vomiting, abdominal pain, confusion, and coma
- A medical emergency that can be life-threatening### Fatty Acid Metabolism
- A fatty acid is a hydrocarbon chain with a terminal carboxyl group and can be saturated or unsaturated.
- Linoleic and linolenic acids are essential for humans.
Fatty Acid Synthesis
- Occurs in the liver following a meal containing excess carbohydrate and protein.
- Carbon required for synthesis is provided by acetyl CoA, energy is provided by ATP, and reducing equivalents by NADPH.
- Citrate carries two-carbon acetyl units from the mitochondrial matrix to the cytosol.
- The regulated step in fatty acid synthesis is catalyzed by Acetyl CoA carboxylase, which requires biotin.
- Citrate is the allosteric activator of Acetyl CoA carboxylase, and long-chain fatty acyl CoA is the inhibitor.
- The enzyme can be activated in the presence of insulin and inactivated by AMPK in response to epinephrine, glucagon, or a rise in AMP.
Fatty Acid Elongation and Desaturation
- Fatty acids can be elongated and desaturated in the ER.
Triacylglycerol Synthesis and Degradation
- Triacylglycerol synthesis occurs in response to ingestion of excess calories as carbohydrate, release of insulin, and protein phosphatase activity.
- Triacylglycerol degradation occurs in response to calorie-deficient diet, release of glucagon, epinephrine, and protein kinase activity.
Fatty Acid Degradation (β-Oxidation)
- Occurs in mitochondria.
- The carnitine shuttle is required to transport LCFA from the cytosol to the mitochondrial matrix.
- A translocase and the enzymes carnitine palmitoyltransferases I and II are required.
- Carnitine palmitoyltransferase I is inhibited by malonyl CoA.
- Once in the mitochondria, fatty acids are oxidized, producing acetyl CoA, NADH, and FADH2.
- The first step in the β-oxidation pathway is catalyzed by one of a family of four acyl CoA dehydrogenases, each of which has a specificity for either short-, medium-, long-, or very-long-chain fatty acids.
Medium-Chain Acyl CoA Dehydrogenase (MCAD) Deficiency
- Causes a decrease in fatty acid oxidation, resulting in hypoketonemia and severe hypoglycemia.
Oxidation of Fatty Acids with an Odd Number of Carbons
- Proceeds two carbons at a time, producing acetyl CoA until three carbons remain (propionyl CoA).
- This compound is converted to methylmalonyl CoA (a reaction requiring biotin), which is then converted to succinyl CoA by methylmalonyl CoA mutase (requiring vitamin B12).
Ketone Bodies
- Liver mitochondria can convert acetyl CoA derived from fatty acid oxidation into the ketone bodies, acetoacetate and 3-hydroxybutyrate.
- Peripheral tissues possessing mitochondria can oxidize 3-hydroxybutyrate to acetoacetate, which can be reconverted to acetyl CoA, thus producing energy for the cell.
Triacylglycerol Synthesis and Degradation
- Triacylglycerol synthesis occurs in the liver cytosol and ER.
- Triacylglycerol degradation occurs in adipose tissue and liver.
Regulation of Fatty Acid and Triacylglycerol Metabolism
- Regulated by hormones and enzymes, such as insulin, glucagon, and epinephrine.
- Insulin stimulates triacylglycerol synthesis, while glucagon and epinephrine stimulate triacylglycerol degradation.
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Compare the synthesis and degradation of long-chain, even-numbered saturated fatty acids in this quiz. Test your knowledge of the pathways and processes involved.
