23B05: Exam Report

Outline the carbohydrate and lipid energy stores of the body (15% marks). Outline the metabolic responses to starvation under the following headings: <24 hours; 24-72 hours; and >72 hours (85% marks)

67% of candidates passed this question.

The first part of this question required the details of carbohydrate and lipid stores with their anatomical locations, biochemical forms, average amount of energy stored.

Under the metabolic responses to starvation, a detailed description was expected of major sources of energy production, associated biochemical processes and their transition from one process to another or one source to another over time, and the hormonal influences that govern this.

A more detailed answer would also include organ specific energy utilisation under a starved state. Overall it was expected that a transition of glycogenolysis to gluconeogenesis to ketogenesis would be described. It would also be important to highlight how an initial protein conservation strategy transitions to eventual protein catabolism and how muscle glycogen, an important store of glucose is unavailable to maintain blood glucose concentrations in starvation.

Pii / 23B05: Outline the carbohydrate and lipid energy stores of the body (15% marks). Outline the metabolic responses to starvation under the following headings: <24 hours; 24-72 hours; and >72 hours (85% marks)

Energy stores

  • Glucose is stored as glycogen in the liver (70-100g) and muscle (400g)
  • 2000kcal energy store (4kcal/g)
  • Glucose in blood represents a small fraction of total energy stores ~5g
  • Fat is stored in the adipose tissue as triglycerides, which can be broken down to glycerol and fatty acids providing 9kcal/g
  • Subcutaneous and visceral adipose tissue
  • Highly variable volume but ~14kg would provide 126000kcal

Metabolic Responses to Starvation

  • Starvation is a state of relative or absolute inadequate energy supply.
  • During starvation the body has to obtain its energy supply from endogenous stores
  • The body tries to conserve energy, minimise loss of protein and provide a constant supply of glucose
  • Certain tissues e.g. brain and nervous tissue, and RBCs require glucose rather than other energy supplies

<24 hours of starvation “glycogenolytic phase”:

  • Glucose oxidation via glycolysis and oxidative phosphorylation provides main energy source.
  • In the first few hours, food would continue to be digested from the GI tract and provide more glucose. As this is depleted, a transition to glycogenolysis would occur.
  • Decreased insulin and increased glucagon stimulates glycogenolysis via glycogen phosphatase.
  • Glycogen is broken down to glucose-6-phosphate which can be dephosphorylated by glucose-6-phosphatase in the liver and transported in the blood as glucose.
  • Muscle lacks glucose-6-phosphatase so can only utilise G6P for glycolysis.
  • Gluconeogenesis begins in order to maintain blood glucose levels due to falling insulin levels, but predominates in the next phase.
  • Note, in the early phase of starvation no protein catabolism is occurring, as the body aims to conserve protein.

24-72 hours of starvation “gluconeogenic phase

  • Glycogen stores become progressively depleted, and gluconeogenesis takes over in providing glucose.
  • Gluconeogenesis occurs predominantly in the liver, but the kidneys have a minor role.
  • Over this phase there is a gradual transition from glycogen to lipid and protein utilisation.
  • Lipolysis increases due to a loss of inhibition of hormone sensitive lipase by insulin, leading to the liberation of glycerol and free fatty acids from the adipose tissue.
  • Additionally, due to reduced glycolysis, levels of glycerol-3-phosphate are depleted, and this additionally leads to lipolysis.
  • The increased glycerol is used for gluconeogenesis in the liver.
  • Additionally, gluconeogenic amino acids and lactate are used for gluconeogenesis. Alanine is the main amino acid used, formed in muscle by transamination of pyruvate. Transported as alanine in the blood then gluconeogenesis to glucose occurs via “alanine-glucose cycle”.
  • The increased free fatty acids undergo beta oxidation in the liver mitochondria to form acetyl-CoA. Large amounts of acetyl-CoA are formed, and are shunted into ketone production. 2 acetyl-CoA molecules condense to form acetoacetate, which can be further metabolised into beta hydroxybutyrate or decarboxylated into acetone. These ketone bodies can be used for energy by various tissues, and their production commences during this phase but predominates in the following phase.
  • Hormones: Insulin levels continue to fall, while glucagon and cortisol and catecholamines increase, promoting lipid mobilization and gluconeogenesis, whilst reducing skeletal muscle protein synthesis. Plasma glucagon level peaks around 4 days of fasting. Growth hormone increases over the first 48 hours then falls.
  • Organ-specific energy utilisation: Brain increases its utilisation of ketone bodies, but still requires some glucose. Heart utilises any energy source so transitions to almost exclusively using ketones.

72 hours of starvation “ketogenic phase”

  • Ketosis Dominance: Ketone bodies become the primary source of energy, reducing glucose dependence.
  • Protein Catabolism: Amino acids from protein breakdown contribute to gluconeogenesis. But falling glucagon levels reduce the amount of gluconeogenesis compared to the above phase. As the transition from gluconeogenesis and protein catabolism to fat catabolism occurs, urinary nitrogen falls.
  • Insulin sensitivity decreases (due to cortisol and catecholamines), conserving glucose for tissues with obligate glucose requirements.
  • Metabolic rate decreases to conserve energy, falling by about 30% due to reduced mass of liver, kidneys and GIT. The thyroid hormone levels fall. Metabolic adaptations aim to conserve energy for vital functions.
  • Cortisol levels rises
  • Brain obtains 50% of its energy from ketone bodies.
  • Water soluble vitamins become deficient rapidly. With prolonged starvation, fat soluble vitamins, electrolytes and micronutrients will also become deficient.

Author: Alex Ashby