Lipid Metabolism Overview
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Questions and Answers

Which condition significantly increases the production and utilization of ketone bodies?

  • Prolonged starvation (correct)
  • High carbohydrate intake
  • Increased physical activity
  • Hyperglycemia

What is the primary form of energy derived from ketone bodies for peripheral tissues?

  • Glucose
  • Fatty acids
  • Acetoacetate and β-hydroxybutyrate (correct)
  • Lactate

Which enzyme is NOT present in the liver that is crucial for the utilization of ketone bodies?

  • Acetoacetyl CoA transferase
  • Thiophorase (correct)
  • Thiolase
  • β-hydroxybutyrate dehydrogenase

In cases of diabetic ketoacidosis, what metabolic shift occurs regarding ketone bodies?

<p>Increased production of ketone bodies (D)</p> Signup and view all the answers

What happens to acetoacetate in the process of ketone body utilization?

<p>It is activated to acetoacetyl CoA (D)</p> Signup and view all the answers

What primarily causes ketonemia?

<p>Excess production of ketone bodies (A)</p> Signup and view all the answers

What does ketonuria indicate?

<p>Active fat metabolism (A)</p> Signup and view all the answers

Which of the following is a characteristic feature of ketosis?

<p>Presence of acetone smell in breath (A)</p> Signup and view all the answers

What effect does starvation have on fatty acid degradation?

<p>Increased degradation to meet energy needs (D)</p> Signup and view all the answers

Why does acetyl CoA accumulate during starvation?

<p>Deficiency of oxaloacetate (D)</p> Signup and view all the answers

In severe diabetes mellitus, what can happen to ketone body concentrations in blood plasma?

<p>Rise to 100 mg/dL or higher (A)</p> Signup and view all the answers

What process is severely impaired in diabetes mellitus leading to increased ketone body production?

<p>Carbohydrate metabolism (A)</p> Signup and view all the answers

What is the normal concentration of ketone bodies in the blood?

<p>1 mg/dL (D)</p> Signup and view all the answers

What is the primary precursor for the synthesis of ketone bodies?

<p>Acetyl CoA (A)</p> Signup and view all the answers

Which enzyme catalyzes the condensation of two moles of acetyl CoA to form acetoacetyl CoA?

<p>Thiolase (D)</p> Signup and view all the answers

In the ketogenesis process, what compound is produced when HMG CoA is cleaved?

<p>Acetoacetate and Acetyl CoA (A)</p> Signup and view all the answers

Which process leads to the formation of acetone during ketogenesis?

<p>Decarboxylation (D)</p> Signup and view all the answers

What role does HMG CoA synthase play in ketogenesis?

<p>It regulates the synthesis of ketone bodies. (D)</p> Signup and view all the answers

What outcome occurs during prolonged starvation that relates to ketogenesis?

<p>Enhanced fatty acid oxidation (B)</p> Signup and view all the answers

Which of the following ketone bodies is formed through reduction by a dehydrogenase?

<p>β-hydroxybutyrate (C)</p> Signup and view all the answers

Where does ketogenesis primarily occur within the cell?

<p>Mitochondrial matrix (C)</p> Signup and view all the answers

Flashcards

Ketones synthesis location

The liver is the primary location for ketone body synthesis.

Ketone precursor

Acetyl CoA is the precursor for ketone synthesis.

Acetyl CoA source

Acetyl CoA comes from fatty acids, pyruvate, or amino acids.

Acetoacetyl CoA formation

Two acetyl CoA molecules condense to form acetoacetyl CoA.

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HMG CoA synthase role

HMG CoA synthase combines acetoacetyl CoA with another acetyl CoA to create HMG CoA. It's a key enzyme controlling ketone production.

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HMG CoA cleavage

HMG CoA lyase splits HMG CoA, producing acetoacetate and acetyl CoA.

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Ketone spontaneous creation

Acetoacetate can spontaneously convert into acetone via decarboxylation.

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Beta-hydroxybutyrate formation

Acetoacetate is reduced to form beta-hydroxybutyrate by a dehydrogenase.

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Ketone body transport

Ketone bodies are water-soluble, allowing them to easily travel from the liver to other tissues.

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Ketone body fuel source

Acetoacetate and β-hydroxybutyrate provide energy for tissues like skeletal muscle, heart muscle, and kidney cortex.

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Mitochondrial need

Tissues lacking mitochondria cannot utilize ketone bodies as an energy source.

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Ketone body significance

Production and utilization of ketone bodies increase during starvation and diabetes mellitus.

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Ketone body for brain

During prolonged starvation, ketone bodies become the main fuel for the brain and central nervous system.

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What is ketonemia?

High levels of ketone bodies in the blood. This happens when the body makes ketones faster than it uses them.

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What is ketonuria?

Ketone bodies are being excreted in the urine. It's a sign that your body is actively burning fat for energy.

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Ketosis

A state where both ketonemia and ketonuria are present. You might smell acetone on the breath.

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Starvation and ketones

During starvation, your body breaks down fat for energy, leading to an overproduction of acetyl CoA. This excess acetyl CoA is converted into ketone bodies.

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Why do ketone levels rise during starvation?

Starvation leads to a deficiency of oxaloacetate needed for the TCA cycle. This pushes the body to make ketones instead of using acetyl CoA efficiently.

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Diabetes and ketones

Insulin deficiency in diabetes disrupts carbohydrate metabolism, forcing the body to rely on fat for energy. This increases ketone production.

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Ketone levels in severe diabetes

Blood ketone levels can reach 100 mg/dL, compared to the normal 1 mg/dL. Urine excretion can also be abnormally high.

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What is the key difference between ketonemia and ketonuria?

Ketonemia refers to excess ketone bodies in the blood, while ketonuria refers to ketones being excreted in the urine.

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Study Notes

Lipid Metabolism

  • Lipids are essential for cell structure and function
  • Lipids are hydrophobic and nonpolar
  • Lipids make up 15-20% of human body weight
  • Triglycerides (TAGs) are the most abundant lipid (85-90%), stored in adipose tissue
  • Lipids serve as energy reserves and insulation for maintaining body temperature

Why Fat as a Fuel Reserve?

  • TAGs are highly concentrated energy stores (9 Cal/g)
  • Fatty acids in TAGs are in a reduced form
  • TAGs are nonpolar and hydrophobic
  • Glycogen (a polar carbohydrate) requires more water for storage (1g glycogen + 2g water)
  • Long-chain fatty acids are the ideal storage fuel
  • Fats support energy needs during food deprivation

Metabolic Profile of Organs

  • Table showing fuel reserves (glucose/glycogen, TAGs, proteins) per organ in a typical 70kg human
    • Blood: 60 kcal glucose/glycogen, 45 kcal TAGs, 0 kcal protein
    • Liver: 400 kcal glucose/glycogen, 450 kcal TAGs, 400 kcal protein
    • Brain: 8 kcal glucose/glycogen, 0 kcal TAGs, 0 kcal protein
    • Muscle: 1200 kcal glucose/glycogen, 450 kcal TAGs, 24,000 kcal protein
    • Adipose Tissue: 80 kcal glucose/glycogen, 135,000 kcal TAGs, 40 kcal protein

Lipid Transport

  • Lipids are insoluble
  • Lipoproteins (lipids associated with proteins) transport lipids in the bloodstream
  • Free lipids are not detectable in the blood because they are not soluble in water

Dynamic State of Body Lipids

  • Lipids are not inert storage compounds
  • Lipids are continuously degraded and resynthesized
  • Adipose tissue stores and releases lipids (energy source) for the body as needed

Fat Mobilization

  • Hormone-sensitive TAG lipase breaks down TAGs
  • Lipases break down DAG and MAG
  • Lipolysis is the complete breakdown of TAGs into glycerol and free fatty acids

Fate of Glycerol and Fatty Acids

  • Glycerol can't be phosphorylated in adipose tissue
  • Glycerol is transported to the liver and converted
  • Free fatty acids enter circulation, bound to albumin, and transported to tissues
  • Tissues use fatty acids for energy

Ketone Bodies

  • Water-soluble and energy-yielding
  • ẞ-hydroxybutyrate is not a true ketone as it does not have a keto group
  • Acetone is an exception to ketone metabolic processes
  • They are synthesized in the liver
  • Enzymes for synthesis in the mitochondrial matrix

Ketogenesis

  • Synthesis of ketone bodies occurs in the liver
  • Acetyl CoA, fatty acids, and amino acids create ketones
  • Ketone bodies are used as an alternative energy source for cells when glucose is insufficient

Utilization of Ketone Bodies

  • Water-soluble (easily transported)
  • Acetoacetate and β-hydroxybutyrate serve as an energy source to peripheral tissues (muscle, cardiac muscle, and renal cortex)
  • Tissues lacking mitochondria cannot use ketone bodies
  • Ketone bodies are important fuel in starvation and diabetes mellitus.

Reactions of Ketone Bodies

  • Reversal of synthesis: β-hydroxybutyrate is converted into acetoacetate by β-hydroxybutyrate dehydrogenase
  • Acetoacetate is activated to acetoacetyl CoA, then cleaved by thiolase into acetyl CoA
  • Thiophorase is absent in the liver

Starvation

  • Increased fatty acid degradation to meet the body's energy needs
  • Overproduction of acetyl CoA when TCA cycle is impaired by oxaloacetate deficiency
  • Excess acetyl CoA and its diversion to ketone body overproduction

Diabetes Mellitus

  • Associated with insulin deficiency
  • Increased lipolysis
  • Accumulation of acetyl CoA leading to ketone body formation
  • High ketone body concentration in the blood and urine
  • Severely high levels of ketone bodies can be fatal

Biosynthesis of Fatty Acids

  • Excess carbohydrates and amino acids are converted to fatty acids
  • De novo fatty acid synthesis predominantly occurs in the liver, kidney, adipose tissue, and lactating mammary glands
  • Enzyme machinery in the cytosol

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