Metabolism Flashcards

1
Q

What are the regulatory steps in glycolysis

A
  1. The phosphorylation of glucose in the muscle and brain by hexokinase (glucokinase in the liver) traps glucose in the cell which maintains the concentration gradient across the plasma membrane and commits glucose to the glycolysis pathway
  2. Phosphofructokinase catalyses the conversion of Fructose-6P to fructose-1,6BP. This is the rate-limiting step of glycolysis and is irreversible.
  3. Pyruvate kinase catalysis the final step in glycolysis from PEP to pyruvate.
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2
Q

Explain the role of the Cori cycle

A

The Cori cycle converts lactate produced in muscles respiring anaerobically to glucose.

In intense muscle activity anaerobic glycolysis dominates. Lactate diffueses out of the cell and is transported to the liver via the blood where is is oxidised to pyruvate, which can then be converted back to glucose. This is returned to the muscles.

This reduces the levels of lactate in muscle and provides more glucose for respiration. This process is not energetically favourable beacuase the muscle gains 2ATP from glycolysis but 6ATP are used in the liver to produce glucose

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3
Q

What are the metabolic signals of the fed state?

A

Increased insulin secretion in response to raised blood glucose

Increased glycogen synthesis

Increased TAG and protein synthesis

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4
Q

What are the metabolic signals of the fasted state?

A

Low insulin:glucagon ratio

Increase in free fatty acids as TAG are broken down

Reduced levels of glycogen in the muscle

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5
Q

What are the metabolic signals of the starved state?

A

Reduction in glucose levels

Depletion of glycogen stores in the muscle and liver

Increase in ketones as FFA are converted in the lvier

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6
Q

Describe the role of the liver in regulating blood glucose

A

In the fed state, when glucose levels are high. Excess blood glucose is transported into hepatocytes via GLUT2 and trapped in the liver by the action of hexokinase and glucokinase (glucose to Glucose-6P). Glucose-6P is then converted to glucose-1P and then UDP-glucose which is the substrate used to create branched glycogen polymers.

In the fasting state glycogen stores in the liver are broken down into glucose and released into the blood. Glucagon promotes lipolysis in liver cells, increasing FFA which can be metabolised by beta oxidation.

In the starved state the liver converts free fatty acids into ketones which can be used as an energy source and produces glucose by gluconeogenesis.

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7
Q

Describe the changes in blood glucose levels following a meal

A

Increase in plasma glucose causes B-cells in
The islets of Langerhans to secrete insulin
(insulin to glucagon ratio favours insulin)

Glycogen synthesis, TAG synthesis and protein
synthesis are stimulated in the tissues
(anabolism)

Glucose is used by the brain as the sole
energy source and uptake is not dependent
on insulin

Muscle and adipose take up and use glucose
but uptake is insulin dependent.

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8
Q

Describe the metabolic changes that occur in the fasted state to increase glucose levels

A

Blood glucose levels fall, insulin secretion stopped

Insulin to glucagon ratio favours glucagon
as insulin levels in the blood fall

Liver glycogen is broken down to
maintain blood glucose promoted by glucagon

TAG are hydrolysed in adipose releasing FFAs

Muscle uses up stored muscle glycogen

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9
Q

Describe the metabolic changes that occur in the starved state

A

Noradrenaline and cortisol levels increase which
activates protein breakdown in muscle releasing
alanine and glutamate

NorA promotes more TAG breakdown and glycerol
release from adipose (rich in sympathetic nerves)

Alanine + glycerol etc are gluconeogenic and liver
uses these to maintain blood glucose

FFA are converted to ketones by the liver
which can be used by the brain
and muscle as an energy source

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10
Q

Functions of insulin

A

Anabolic effects. Promotes synthesis and energy storage

Increase liver glycogen synthesis
Increases glycolysis
Increase glucose uptake in peripheral tissues
Increase amino acid uptake and protein synthesis

Inhibits protein breakdown
Increases lipogenesis
Inhibits lipolysis

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11
Q

Functions of glucagon

A

Catabolic functions, releases glucose inhibits synthesis

Stimulates glycogen breakdown
Stimulates gluconeogenesis

Stimulates protein breakdown

Inhibits lipogenesis
Activates lipolysis and ketone synthesis

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12
Q

How does the kinetic activity of hexokinase and glucokinase relate to their functions?

A

hexokinase enzymes are found in all tissue types while glucokinase is found in the liver.

hexokinase and glucokinase both phosphorylate glucose to glucose-6P, thereby trapping it within the cell which feeds into the glycolysis pathway and maintains the glucose concentration gradient.

hexokinase has a high affinity for glucose, (Km=0.05mM) which means that even if the intracellular concentration of glucose is low, the reaction can still proceed so cells can produce ATP.
At physiological concentrations of glucose (5mM), the hexokinase enzyme is working at Vmax and is relatevely insensitive to changes in blood glucose over this level. High levels of glucose-6P inhibit hexokinase

Glucokinase has a lower affinity for glucose (Km=10mM) which enables the liver to respond to high levels of glucose in the blood and unlike hexokinase is not inhibited by glucose-6P. Excess glucose taken up by the liver is converted into Glucose-1P and stored as glycogen.

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13
Q

What is the key step in the gluconeogenesis pathway?

A

Carboxylation of pyruvate to oxaloactetate (requires biotin as a co-factor)

Oxaloacetate is then converted to phosphoenolpyruvate

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14
Q

4 key molecules derived from tyrosine

A

Dopamine

Epinephrine

Melanin

thyroxine

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15
Q

What is the effect of growth hormone on metabolism?

A

Increases protein synthesis

Increases fatty acid metabolism

Anti-insulin effect in muscle

Net result is to increase body protein

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16
Q

What is the effect of thyroid hormone on metabolism?

A

Catabolic effects:

Stimulates the uptake of glucose, glycolysis and gluconeogenesis.

Increases lipid mobilisation from fats and lowers cholesterol.

17
Q

What is the effect of cortisol on metabolism?

A

Increases protein breakdown and reduces protein synthesis

Increases breakdown of fat