MBBS Stage 1: Liver and Gluconeogenesis

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Questions and Answers

What is the primary reason why glucose is considered an important metabolic fuel?

It is a source of NADPH for synthetic reactions and drug metabolism

It is a source of pentose sugars for synthetic reactions

It is the preferred fuel source for the brain and red blood cells

It is the primary source of energy for all tissues (correct)

What is the normal range of blood glucose concentration in healthy adults?

5.5-6.5 mM

3.9-6.2 mM (correct)

2.5-3.5 mM

4.4-5.5 mM

What is the consequence of blood glucose concentration dropping to 2.5 or less?

Increased glucagon secretion

Coma and death (correct)

Dehydration and wasting of body tissue

Increased insulin secretion

What is the role of glucose in the liver?

All of the above Signup and view all the answers

What is the main pathway involving glucose in skeletal muscle?

Glycolysis and glycogen synthesis Signup and view all the answers

What is the function of glucose in the heart and brain?

Energy production through glycolysis and the TCA cycle Signup and view all the answers

What is the consequence of high glucose concentrations in the blood?

Direct cell damage or accumulation of toxic by-products Signup and view all the answers

What is the role of glucose-6-phosphate dehydrogenase in the pentose phosphate pathway?

Production of NADPH Signup and view all the answers

What is the significance of glucose as a metabolic fuel?

All of the above Signup and view all the answers

What is the commonest human enzyme deficiency?

Glucose-6-phosphate dehydrogenase deficiency Signup and view all the answers

What is the approximate number of people worldwide with G6PD deficiency?

400 million Signup and view all the answers

What is the primary function of the pentose phosphate pathway in the liver?

NADPH, pentoses Signup and view all the answers

Which of the following is NOT a source of blood glucose in a normal person?

Fatty acids Signup and view all the answers

What is the primary cause of haemolytic anaemia in individuals with G6PD deficiency?

Ingestion of fava beans Signup and view all the answers

What is the characteristic of the Mediterranean variant of G6PD deficiency?

Higher susceptibility to favism Signup and view all the answers

What is the primary function of gluconeogenesis in the liver?

Glucose production for other tissues Signup and view all the answers

Why is gluconeogenesis not simply the reversal of glycolysis?

Because there are 3 irreversible reactions in glycolysis Signup and view all the answers

What is the fate of glucose in the liver after ingestion of a 100g glucose load?

It is released into the bloodstream Signup and view all the answers

Which of the following enzymes is not involved in the conversion of pyruvate to PEP in gluconeogenesis?

Phosphofructokinase Signup and view all the answers

What is the primary function of insulin in the body?

To promote the synthesis and storage of glucose Signup and view all the answers

Which of the following is NOT a way to mobilize substrate for gluconeogenesis?

Glucose from glycogen breakdown Signup and view all the answers

What is the primary function of the Cori cycle and Glucose-alanine cycle?

To regulate blood glucose levels Signup and view all the answers

Which of the following enzymes is involved in the conversion of PEP to pyruvate in glycolysis?

Pyruvate kinase Signup and view all the answers

What is the primary function of glucagon?

To break down stored glycogen in the liver Signup and view all the answers

What is the effect of insulin on glycogen synthesis in the liver?

Activation of glycogen synthase Signup and view all the answers

What is the effect of glucagon on blood glucose levels?

Increase in blood glucose levels Signup and view all the answers

What is the effect of insulin on glucose uptake in muscle?

Increase in glucose uptake Signup and view all the answers

What is the effect of glucagon on fatty acid oxidation in the liver?

Increase in fatty acid oxidation Signup and view all the answers

What is the effect of insulin on protein synthesis in muscle?

Increase in protein synthesis Signup and view all the answers

What is the effect of glucagon on glycogenolysis in the liver?

Increase in glycogenolysis Signup and view all the answers

What is the effect of insulin on fatty acid synthesis in the liver?

Increase in fatty acid synthesis Signup and view all the answers

What is the effect of glucagon on amino acid uptake in the liver?

Increase in amino acid uptake Signup and view all the answers

Study Notes

Glucose: Importance and Sources

Glucose is the preferred fuel source for all tissues, with some tissues having a continuous dependence on glucose.
The normal physiological circulating glucose concentration is 3.9-6.2 mM, with an average fasting concentration of 4.4-5 mM for most adults.
If blood glucose concentration drops to 2.5 mM or less, coma and death can result, while prolonged elevated levels can lead to dehydration, wasting of body tissue, and eventually death.

Roles of Glucose

Glucose is a source of energy, producing 2 ATP through glycolysis and 31 ATP through the citric acid cycle.
Glucose is a source of NADPH, needed for synthetic reactions, fatty acid synthesis, and drug metabolism.
Glucose is a source of pentose sugars for synthetic reactions, such as nucleotide and DNA synthesis.
Glucose is a source of carbon for other sugars and glycoconjugates.

Advantages and Disadvantages of Glucose as a Metabolic Fuel

Advantages: water-soluble, can cross the blood-brain barrier, and can be oxidized anaerobically.
Disadvantages: relatively low yield of ATP per mole compared to fatty acids, osmotically active, and can directly damage cells or lead to toxic by-products in high concentrations.

Glucose Metabolism in Different Tissues

Skeletal muscle: glycolysis for anaerobic muscle contraction, glycolysis/TCA cycle for energy production, and glycogen synthesis/degradation for energy storage.
Heart/brain: glycolysis/TCA cycle for energy production.
Adipose tissue: glycolysis for glycerol production and TAG synthesis.
Erythrocytes: glycolysis for energy production, and pentose phosphate pathway for NADPH production.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

X-linked hereditary disorder affecting over 400 million people worldwide, particularly in African, Middle Eastern, and South Asian populations.
Triggers for hemolytic anemia in G6PD-deficient individuals include favism, resulting from the ingestion of fava beans.

Glucose Metabolism in the Liver

Glycolysis/TCA cycle for acetyl-CoA production.
Pentose phosphate pathway for NADPH and pentose sugar production.
Glycogen synthesis/degradation for glucose storage and release.
Gluconeogenesis for glucose production from non-carbohydrate sources.

Gluconeogenesis

Occurs in the liver during carbohydrate deprivation, synthesizing glucose from non-carbohydrate sources such as lactate, glycerol, and glucogenic amino acids.
Not simply the reversal of glycolysis, requiring bypassing of three irreversible reactions in glycolysis.

Regulation of Gluconeogenesis

Mobilization of substrate from fat breakdown and muscle protein breakdown.
Activation of enzymes, including G6Pase, F1,6bisPase, and PEPCK, and pyruvate carboxylase by acetyl-CoA.

Blood Glucose Maintenance

Insulin, glucagon, and adrenaline (and to a lesser extent cortisol) signal and coordinate the activities of the liver, adipose tissue, and muscle tissue to maintain physiological blood glucose concentrations.
Insulin promotes synthesis and storage, while glucagon promotes degradation of stored fuel.

Insulin and Glucagon

Insulin: anabolic hormone promoting synthesis and storage, with effects on liver, muscle, and adipose tissue metabolism.
Glucagon: catabolic hormone promoting degradation of stored fuel, with effects on liver, muscle, and adipose tissue metabolism.

Glucose Tolerance Curves

Normal glucose tolerance curves show a rapid increase in blood glucose after a meal, followed by a rapid decrease to basal levels.
Diabetes type 1 and type 2 show impaired glucose tolerance, with a slower and more prolonged increase in blood glucose after a meal.

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Description

Understand the importance of glucose as a metabolic fuel, sources of glucose, and the process of gluconeogenesis in the liver. Learn about blood glucose homeostasis and the roles of different organs in glucose regulation.