Coordinating metabolism - Starvation Flashcards

1
Q

what are the concepts of energy homeostasis under starvation?

A
  • maintenance of blood glucose levels to preserve brain function
  • sparing of glucose by multiple tissues
  • making alternative fuels available
  • provisions of special fuel needs of each tissue
  • sparing of structural body proteins
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2
Q

What happens to fuel levels in blood during starvation?

A
  • ketone production ramped up (brain can use these as an alternative fuel to glucose during starvation, this allows glucose to be spared)
  • glucose levels maintained/very stable
  • increased FFAs
  • protein utilised initially then conserved (can be observed by the drop in urinary ammonia - as to use proteins for fuel you use the carbon skeleton and cleave off the amino group which is then excreted as ammonia or urea in the urine)
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3
Q

What studies were done to find out most of the information we know about starvation?

A

Minnesota starvation experiment:
- during the war, wanted to find out side effects of starvation and if people could recover
- the men lost fat and muscle, were tired and became very irritable but recovered on refeeding
Cahill’s studies:
- starved obese patients for 6 weeks and measured metabolites over time
- this is were the data on the fuel levels in the blood was from

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4
Q

what is the process for what systems are switched to from fed, to fasting to starvation?

A

Will go from glucose in food, to glycogen stores in liver, and then gluconeogenesis (liver makes new glucose), then fat stores

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5
Q

what are the five phases of sources of glucose from fed to starving

A

1.
- origin of blood glucose: exogenous
- tissues using glucose: all
- major fuel of brain: glucose
2.
- origin of blood glucose: glycogen, hepatic gluconeogenesis
- tissues using glucose: all except liver. muscle and adipose tissue at diminished rates
- major fuel of brain: glucose
3.
- origin of blood glucose: hepatic gluconeogenesis, glycogen
- tissues using glucose: all except liver. muscle and adpose tissue at rates intermediate between 2 and 4
- major fuel of brain: glucose
4.
- origin of blood glucose: gluconeogenesis, hepatic and renal
- tissues using glucose: brain, RBCs, renal medulla. small amount by muscle
- major fuel of brain: glucose, ketone bodies
5.
- origin of blood glucose: gluconeogenesis, hepatic and renal
- tissues using glucose: brain at a diminished rate, RBCs, renal medulla
- major fuel of brain: ketone bodies, glucose

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6
Q

describe the inter tissue relationships during starvation

A
  • new glucose is made in the liver from gluconeogenic precursors ie. glycerol from fat (adipose) and pyruvate from alanine (muscle).
  • mobilisation of fat from adipose
  • influx of FFAs into liver and subsequent beta-oxidation increases acetyl-CoA which drives ketogenesis (making ketone bodies)
  • ketone bodies provide acetyl-CoA from CAC and ATP generation in brain and muscle
  • these metabolic adaptions are driven by glucagon in response to low glucose and potentiated by cortisol and adrenaline
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7
Q

describe starvation metabolism

A
  • gluconeogenesis is liver prominent
  • fat becomes a prominent fuel for many tissues
  • ketones made in liver from catabolism of fat becomes alternative and efficient fuel for brain (also serves to spare glucose)
  • mobilisation of muscle protein is spared
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8
Q

how does glucagon activate fat mobilisation and gluconeogenesis?

A

fat mobilisation:
- glucagon binds GPCR
- signal transduction
- activates PKA
- activates hormone sensitive lipase (using ATP)
- hormone sensitive lipase cleaves a TAG into glycerol and FFAs

gluconeogenesis:
- glucagon binds to GPCR
- inhibition of AKT protein
- so that it can’t phosphorylate FoxO1 transcription factor
- FoxO1 transcription factor switches on PEPCK gene, which makes a very highly regulated enzyme that activates glyconeogenisis
FoxO1 is a transcription factor that activates gluconeogenic genes

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9
Q

describe the overall process of gluconeogenesis

A
  • occurs mainly in liver (some in kidney)
  • synthesis of glucose from:
    - lactate from RBCs and muscle
    - alanine from muscle protein
    - glycerol from adipose tissue
  • stimulated by glucagon
  • fatty acid oxidation provides the energy and reducing power
  • brain uses most of the glucose
  • inhibited by alcohol
  • basically glycolysis in reverse but also using glycerol (for middle of pathway) and alanine (for pyruvate) as most of the enzymes that catalyse the reactions can also do the backwards reaction too
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10
Q

describe the effects of alcohol metabolism on gluconeogenesis

A

for every molecule of alcohol, two molecules of NADH are produced.
This increases the NADH to NAD+ ratio
And drives gluconeogenic precursors away from gluconeogenesis:
- pyruvate to lactate
- ocaloacetate to maltate
This inhibits gluconeogenesis, lowers blood glucose, lowers pH and can eventually cause coma.

Acetaldehyde is the middle/intermediate thing. is toxic and what causes a hangover

Don’t drink too much especially if you are heading into starvation mode
Your brain will not function well under these conditions
Have something to eat

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11
Q

describe the synthesis of ketone bodies

A
  • synthesised in the liver from fatty acids
  • used by starving brain as energy source

Mobilisation of TAG from adipose tissue:
- FFAs undergo beta-oxidation to make acetyl-CoA
- acetyl-CoA undergoes ketogenesis to make acetoacetate and in a reversible reaction also beta-hydroxybutyrate which are both ketone bodies

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12
Q

ketone body concentrations

A

Fed state: <0.1 mmol/L
Fasted state: 0.3 mmol/L
Starved state: 10 mmol/L
Type 1 diabetes ketoacidosis: >30 mmol/L

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13
Q

what were the questions raised from the James Scott surviving on a chocolate bar scenario and their answers?

A

How was he Abel to survive for so long?
- fuel stores (especially fat) and adaptability/flexibility of fuel storage
Hod did his brain continue to function?
- glucose (gluconeogenesis) and ketones (ketogenesis)
What happened to his fat stores?
- mobilised to fat acids ad glycerol
What happened to his muscles?
- proteolysis of amino acids to provide carbon backbones for energy and glucose production
Did the energy from the chocolate bar help him survive?
- for about 1 hr

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