Integrated Flashcards

1
Q

Describe gluconeogenesis

A

Pyruvate to oxaloacetate (pyruvate carboxylase)

  • Oxaloacetate to phosphoenolpyruvate (PEP carboxylase)
  • To fructose 1,6 bisphosphate (lose 6 ATPs)
  • To F6P (F16bP phosphotase)
  • To G6P
  • To glucose (G6 phosphotase)

overall glycolysis = +2ATP
overall gluconeogensis = - 6ATP

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2
Q

what are some general metabolic features of specialised tissues?

  • muscle
  • brain and nervous tissue
  • adipose tissue
  • heart
  • liver
A
  • muscle = periods of high ATP demand during vigorous contraction - relies on carbohydrates and fat oxidation
  • brain and nervous tissue = constant high ATP requirement
  • adipose tissue =
    long term storage site for fats
  • heart = can oxidise fast and carbs
  • liver = the bodys main store of carbohydrates and blood glucose
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3
Q

how does skeletal muscle receive energy during
light contractions :
vigorous contractions:

A

light - oxidative phosphorylation using oxygen and glucose

vigorous -
too much ATP is needed, so glycogen stores in the muscle is broken down and pyruvate is converted to lactate which travels to the liver

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4
Q

how does the brains metabolism work?

A
  • requires a constant supply of glucose
  • it cannot metabolise fatty acids
  • ketone bodies can substitute for glucose
  • the brain can only metabolise glucose and ketone bodies
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5
Q

how does the cardiac muscle respire?

A
  • only aerobic respiration
  • therefore lots of mitochondria
  • can use TCA cycle substrates
    like free fatty acids and ketone bodies
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6
Q

how does the liver respire?

A
  • immediate recipients of nutrients are absorbed at the intestines
  • Carries out many metabolic processes
  • Has a role in maintaining blood glucose levels at 4.0-5.5mM
  • there is a store of glycogen
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7
Q

what happens to excess glucose in glycolysis?

A
  • ## G6P can be converted to glycogen which might be stores in the organ or it is transported to liver
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8
Q

what happens if the TCA cycle slows down because of anaerobic respiration?

A
  • there is a build up of pyruvate

- pyruvate is then converted to lactate which can be used as an alternate fuel source

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9
Q

what happens to excess acetyl CoA ?

A

excess acetyl CoA can be converted to ketone bodies
- which might be used by the brain when there is no glucose

  • or it might be converted to fatty acids and cholesterol which can then be stored
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10
Q

what is gluconeogenesis?

A

Process of making GLUCOSE or GLYCOGEN from OXALOACETATE

- this requires ATP hydrolysis

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11
Q

what happens in protein metabolism?

A
  • protein is broken down into amino acids
  • the amino acids can feed into the glycolysis or TCA cycle in the form of pyruvate or acetyl CoA
  • The acetyl CoA that is produced can be channelled to produce fatty acids and ketone bodies
  • as it is able to generate pyruvate the breakdown of protein can be used to start gluconeogenesis
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12
Q

what happens to the muscle cells when they have increased ATP demand?

A
  • muscles contract more
  • because contractions increase the demand for glucose and hence an increase in demand for glucose transport
  • This is solved by an increase in the number of glucose transporters in the plasma membrane, transporting glucose into the muscle cell
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13
Q

what does adrenalin do?

A
  • Causes an increase in muscle glycolysis - so more ATP can be produced
  • increases gluconeogenesis as the demand for ATP increases more glucose is needed.
  • increases the release of fatty acids so more ATP can be created
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14
Q

what happens in anaerobic respiration?

A
  • TCA cycle slows and stops
  • ATP demand cannot be matched by oxygen delivery • anaerobic respiration.
  • muscles start breaking down their glycogen reserves
  • so more glucose can enter the TCA cycle
  • Because of the increased rate of glycolysis you get an accumulation of pyruvate and hence an increase in the conversion of pyruvate to lactate.
  • lactate is moved to the liver to prevent the acidosis of the blood
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15
Q

Control of glucose metabolism in the muscle and the liver?

A
  • this is carried out by
    muscle = hexokinase 1
    liver = hexokinase 4
  • they both convert glucose to G6P but the difference is that they both have very different rates of reaction
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16
Q

describe hexokinase 1 :

muscle

A
  • Hk I in muscles has a high glucose affinity
  • Hk I activity rises rapidly in response to rising glucose concentration
  • Hk I reaches max activity at quite low glucose concentrations
  • highly sensitive to G6P inhibition and if G6P gets inhibited it will also get inhibited
17
Q

describe hexokinase 4 (liver)

A
  • has a low glucose affinity
  • and converts glucose much slower than in the liver
  • This means muscle will preferably convert glucose to G6P where glucose is available
  • Hk IV is less sensitive to G6P
18
Q

what does insulin do?

A

secreted when glucose levels rise - stimulates uptake and use of glucose and storage of glycogen and fat

19
Q

what does glucagon do?

A

secreted when glucose levels fall - stimulates gluconeogenesis and the breakdown of glycogen and fat

20
Q

what does adrenaline do?

A

strong and fast metabolic effects to mobilise glucose for ‘fight or flight’

21
Q

what do glucocorticoids do?

A

steroid hormones that increase synthesis of metabolic enzymes concerned with glucose availability

22
Q

what happens in T1 diabetes and T2 diabetes?

A
  • Type I - cannot make insulin

* Type II - reduced responsiveness to insulin

23
Q

what are complications of diabetes?

A
  • Hyperglycaemia - causing progressive tissue damage
  • Increase in plasma fatty acids and lipoproteins - possible cardiovascular complications
  • Increase in ketone bodies - possible acidosis
  • Hypoglycaemia - possible coma if insulin dosage is not correctly controlled
24
Q

how does the body recognise glucose in the blood stream?

A
  • the body does not recognise any glucose in the blood stream because the signalling pathway does not work
  • So glucose is not taken up into the muscle or the liver.
  • the body thinks it is starving
  • glycogen –> glucose
  • protein –> amino acids
25
Q

what happens when the production of glucose is exacerbated?

A
  • Gluconeogenesis leads to the production of glucose, which is not detected by the tissue, and hence it aggravates the hyperglycaemia.
  • Triglycerides in adipose tissue are broken down releasing glycerol and free fatty acids
  • these free fatty acids undego b oxidation and produce ketone bodies
  • excessive production of ketone bodies leads to diabetic ketoacidosis
26
Q

how do pancreatic b cells regulate hormone secretion?

A
  • Glucose transported into the beta cell and is metabolised to produce ATP.
  • ATP is also a signalling molecule within the cell.
  • ATP binds to the potassium ATP channel at the cell surface and regulates its function.
  • closing the potassium ATP channels the cell becomes depolarised which causes the opening of Ca2+ ion channels so Ca2+ moves in
  • this causes insulin and ZINC to be released to the blood stream

-

27
Q

what is glucagon like peptide 1 ?

A
  • drug that treats T2 diabetes
  • but if there is an increase in plasma glucose concentrations then GLP1 accentuates the glucose response and leads to more release of insulin.
28
Q

on having a meal what is the blood glucose controlled by?

A
  • Islets of Langerhans Increased secretion of insulin and reduced secretion of glucagon
  • liver
    increased glucose intake
  • muscle
    increased glucose uptake and glycogen synthesis
  • adipose tissue
    increased triglyceride synthesis
29
Q

what happens after a meal in terms of enzymes?

A
  • Insulin increases the activity of Hk IV and decreases the activity of Glucose-6-Phosphatase.
    Overall increase in the storage activity
30
Q

what is glucagon’s significance in type 2 diabetes?

A
  • Important protection against hypoglycaemia.
  • liver is the major site of action
  • glucagon stimulates gluconeogenesis and glycogenolysis
31
Q

how do the alpha and beta cells regulate the release of hormones?

A
  • Insulin inhibits glucagon release
32
Q

what happens after a meal when the blood glucose starts to fall?

A
  • Islets of Langerhans - increased glucagon secretion + decreased insulin secretion
  • Liver - glucose production + glycogen breakdown + gluconeogenesis
  • Utilisation of fatty acid breakdown as alternative substrate for ATP production
  • Adrenaline released to procude more glucose
33
Q

what happens after prolonged fasting which cant be maintained by glycogen reserves?

A
  • Glucagon/Insulin ratio increases further
  • the triglycerides are hydrolysed to provide fatty acids for metabolism
  • Protein breakdown provides amino acid substrates for gluconeogenesis
  • Liver - produces ketone bodies from fatty acids and amino acids