30 Questions
What is the ultimate fate of fatty acids released from monoacylglycerols through the action of monoacylglycerol lipase?
They are used for fatty acid oxidation
What is the primary location where ketone bodies are formed?
Liver mitochondria
What is the term used to describe the three biosynthetically related products formed during ketogenesis?
Ketone Bodies
What is the result of high rates of fatty acid oxidation in the liver?
Formation of ketone bodies through ketogenesis
What is the role of epinephrine in fatty acid oxidation?
Binding to its receptor and activating adenylate cyclase
What is the primary function of ketone bodies in the body?
Serving as an important source of metabolic energy
What is the primary fate of the small amount of acetone formed in the body?
It is exhaled through the lungs
What is the result of oxaloacetate depletion in the liver during fasting or carbohydrate starvation?
Impeded entry of acetyl-CoA into the Krebs cycle
What is the first step in the formation of ketone bodies?
Condensation of two acetyl-CoA molecules to form acetoacetyl-CoA
Which enzyme is found in large amounts only in the liver and is involved in the formation of ketone bodies?
HMG-CoA synthase
What is the result of the cleavage of HMG-CoA?
Formation of acetoacetate and acetyl-CoA
Which enzyme catalyzes the interconversion of acetoacetate and β-hydroxybutyrate?
β-Hydroxybutyrate Dehydrogenase
What is the result of the spontaneous decarboxylation of acetoacetate?
Formation of acetone
What is the consequence of low carbohydrate utilization or deficiency?
Reduced level of oxaloacetate
What is the primary source of fuel for the heart and skeletal muscle in the early stages of starvation?
Ketone bodies
What is the enzyme responsible for converting acetoacetate to β-hydroxybutyrate?
β-hydroxybutyrate dehydrogenase
What is the role of acetoacetate and β-hydroxybutyrate in the biosynthesis of neonatal cerebral lipids?
They serve as major substrates for the biosynthesis of neonatal cerebral lipids
What is the process by which extrahepatic tissues utilize ketone bodies?
Conversion of β-hydroxybutyrate to acetoacetate and of acetoacetate to acetoacetyl-CoA
What is the primary cause of diabetic ketoacidosis?
Reduced supply of glucose and increased fatty acid oxidation
What is the effect of acidification of the blood due to the increased production of ketone bodies?
Impairs the ability of hemoglobin to bind oxygen
What is the primary source of energy during healthy regular life?
Glucose breakdown
What is the warning sign of diabetic ketoacidosis in urine?
Presence of ketones
What is the effect of ketone bodies on the body?
They poison the body
What is the result of the increased production of acetyl-CoA in diabetic ketoacidosis?
Increased production of ketone bodies
Which enzyme is responsible for acting on acetoacetate in the process of ketogenesis?
Succinyl-CoA transferase
What is the primary function of ketoacyl-CoA-transferase in extra-hepatic tissues?
To provide a fuel source during prolonged fasting and starvation
What determines the fate of fats in the liver?
The availability of glycerol-3-phosphate
What is the fate of acetyl-CoA when the demand for ATP is high?
It is further oxidized to CO2
What regulates the level of fat oxidation in the liver?
The regulation of ACC through phosphorylation
Why is the liver unable to utilize ketone bodies?
Because it lacks ketoacyl-CoA-transferase
Study Notes
Untreated Type 1 Diabetes (Insulin Dependent)
- Diabetic ketoacidosis (DKA) occurs due to a reduced supply of glucose and a concomitant increase in fatty acid oxidation.
- DKA results from the inability of peripheral tissues to oxidize ketone bodies produced in the liver.
Acidification of the Blood
- Ketone bodies are relatively strong acids (pKa around 3.5) that lower the pH of the blood.
- Acidification of the blood impairs the ability of hemoglobin to bind oxygen.
Ketocidosis in Diabetes
- Ketoacidosis refers to dangerously high levels of ketones in the body.
- Ketones poison the body, and their presence in urine is a warning sign that diabetes is out of control or that the individual is very sick.
Signs of Diabetic Ketoacidosis
- Elevated glucose level
- Dry or flushed skin
- Vomiting, nausea, and abdominal pain
- Breathing difficulties
- Fruity odor of breath
- Confusion
Metabolic Paths
- Glycolysis: glucose breakdown provides energy during healthy regular life
- Fat Oxidation: mobilization of fatty acids and breakdown gives energy from fat stores during exercise
- Ketogenesis: leads to diabetic ketoacidosis during diabetes mellitus
Ketogenesis
- Ketone bodies are formed in the liver mitochondria during high rates of fatty acid oxidation
- Acetoacetate, β-hydroxybutyrate, and acetone are the three biosynthetically related products of ketogenesis
- Acetoacetate and β-hydroxybutyrate are formed from acetyl-CoA in the liver mitochondria
Formation of Ketone Bodies
- Ketogenesis begins with the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA
- Acetoacetyl-CoA and an additional acetyl-CoA are converted to β-hydroxy-β-methyl-glutaryl-CoA (HMG-CoA)
- HMG-CoA is cleaved into acetoacetate and acetyl-CoA
Regulation of Ketogenesis
- Control in the release of free fatty acids from adipose tissue directly affects the level of ketogenesis in the liver
- The level of fat oxidation is regulated hormonally through phosphorylation of ACC, which may activate or inhibit it
Test your knowledge of metabolic pathways, including glycolysis, fat oxidation, and ketogenesis. This quiz covers the overview of general metabolism, recap of beta oxidation, and the role of epinephrine in hormone-sensitive lipase activation.
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