Control of metabolism Flashcards

1
Q

What is metabolism?

A

Extract energy from nutrients
Use energy for work and synthesis
Store excess energy

Two pathways
- Anabolic –> build large molecules
- Catabolic –> break down large molecules

Two states
- Absorptive –> ‘fed’ - anabolic
- Post-absorptive –> ‘fasted’ - catabolic

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2
Q

What are the energy stores?

A

Glycogen store: –> 600g maximum
- Liver
- Muscle

Adipose:
- No limit of fat that can be stored

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3
Q

What is the oral glucose tolerance test?

A

Glucose drink containing 75g
- measures the amount of glucose being absorbed
- monitors glucose levels in the blood over the next two hours

In comparison to the placebo group (orange squash), there is a larger peak of blood glucose, placebo remains quite constant, similar to that of fasting conditions. Decrease after peak following insulin release from pancreatic beta cells.

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4
Q

How does the liver produce glucose?

A

Glyconeolysis –> breakdown of glycogen stores
- Glucose-6-phosphate –> either continue to pyruvate or becomes glycogen

Gluconeogenesis –> glucose synthesised from non-carbohydrate precursors in the liver

Availability of glucose in liver and muscle cells determines which of these enzymes is activated or inhibited

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5
Q

What is gluconeogensis?

A

Formation of glucose in the liver from non-carbohydrate precursors.
- main precursors are lactate, glycerol, alanine, and glutamine
- requires energy
- activation of enzymes in these processes is determined by levels of glucose and pyruvate and enzymes controlling them

Lactate produced in anaerobic respiration

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6
Q

How is fat metabolised?

A
  • Body fat is stored mostly in adipocytes and triglycerides. Clusters of adipocytes form adipose tissue
  • Release of fatty acids and glycerol into bloodstream allow energy production
  • 2.5x more ATP from fat than CHO
  • Excess glucose can readily be converted and stored as fat
  • Breakdown is known as lipolysis
  • Low glucose stores/ levels activate lipolysis. Glycerol converted into glucose

Fatty acids can be used to for some keto-acids used to form some amino acids

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7
Q

What controls metabolism?

A

The ratio of insulin and glucagon

Glucose levels alters the ration

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8
Q

What happens when insulin levels are higher in the ratio?

A

Anabolic state
Absorptive state

  • Increase glucose oxidation
  • Increase glycogen synthesis
  • Increase fat synthesis
  • Increase protein synthesis
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9
Q

What happens when glucagon levels are higher in the ratio?

A

Catabolic state
Post-absorptive state
Fasted - low glucose levels

  • Increase glycogenolysis
  • Increase gluconeogenesis
  • Increase ketogenesis
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10
Q

What occurs in the post-absorptive state?

A

e.g before breakfast
Glucagon increases
Blood glucose fairly constant at 5mmol/min
Blood glucose maintained by
- glycogenolysis
- gluconeogenesis
50:50 balance between processes

Glucagon mechanism

Low blood glucose levels –> alpha cells from pancreas release glucagon –> signals liver to break glycogen into glucose –> bring glucose levels back to homeostasis

Insulin levels low –> uptake of glucose to adipose and muscle is low

Glucagon effects in liver
- Glycogenolysis
- Gluconeogenesis
- Synthesis of ketones

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11
Q

What is the effect of glucagon on carbohydrate and fat metabolism?

A

Stimulates lipolysis to use fat as fuel
Stimulates gluconeogenesis in the liver
Inhibits glycogen synthesis
Promotes the conversion of fatty acids to ketone bodies in the liver –> enough energy for brain, can use glucose and ketones

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12
Q

What happens to fat metabolism in the post-absorptive phase?

A

Low insulin sends signals that energy must be made from triglycerides –> FA and glycerol

Brain:
- Glucose oxidation

Muscle:
- Low insulin prevents glucose uptake from plasma
- HIgh levels of plasma FFA
- FA taken up by liver and muscle and enter mitochondria for oxidation

Minimum energy from glucose will go to the brain

Hydrolysis of triglycerides into FFA release in the bloodstream
- HSL (hormone-sensitive lipase) stimulated by glucagon/ low insulin
- Activate triglyceride breakdown into glycerol and fatty acids
- Glycerol to the liver to produce energy
- FFA released into the blood –> can be converted to ketone bodies to supply energy to the brain

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13
Q

How do ketones provide the brain with energy?

A

From lipolysis –> FFA undergo beta oxidation –> become AcetylCoA –> enter krebs cycle
-> in liverAcetylCoA converted to Ketones –> energy for the brain

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14
Q

What occurs in the absorptive phase?

A

Anabolic state
- Suppression of mobilisation of endogenous fuels
- Production of glucose by the liver is inhibited
- FFA release from adipose is inhibited
- Body preserves its stores
- Starts to use incoming fuels and stores excess

Insulin excretion after feeding is caused by:
- secretion of secretin and CCK from duodenum in response to food
- rise in plasma glucose and amino acids following the absorption of digested food

GLUT4 carrier made present in muscle and adipose tissue, activity influenced by insulin
- in basal conditions, found in membrane and cytosol
- insulin increases the movement of GLUT4 translocation by 10-20x

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15
Q

What are some consequences of increased insulin?

A
  • Increased uptake and utilisation of glucose by cells
  • Increased storage of glucose as glycogen
  • Increased amino acid uptake and protein synthesis –> stimulates enzymes involved in protein synthesis, inhibits those involved in protein catabolism
  • Increased uptake and storage of fat by adipose tissue
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16
Q

What are some effects of insulin on carbohydrate metabolism?

A
  • Large proportion of glucose absorbed is taken up by liver and stored
  • Stimulates glycogen synthesis and inhibits glycogen breakdown –> increasing carbohydrate stores
  • Stimulates enzymes to promote glucose utilisation in the production of ATP
  • Inhibits gluconeogensis
17
Q

What are some key biochemical events from insulin?

A

Muscle
- Increases glucose uptake
- Increase glycogen synthesis
- Increases glucose utilization

Adipocytes
- Increases glucose uptake
- Stimulates storage of fat as TG
- Inhibit fat breakdown

Liver
- Promote storage of glucose as glycogen

18
Q

How is the metabolism of glucose, protein, and fat regulated?

A