Molecular Biology - Integration of Metabolism Flashcards

1
Q

AtherEnergy intake

A

Has to be tightly coordinated with energy expenditure ; different tissues have different environments

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2
Q

Muscles

A

Very high periods of ATP requirement and relies upon carbohydrates and fatty acid oxidation

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3
Q

How much of total body weight is muscle?

A

40%

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4
Q

Brain and nervous

A

Has a continuous ATP requirement ; cannot utilise fatty acids as a fuel source - 2% of total body weight

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5
Q

Adipose tissue

A

Long term storage site for triglycerides

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6
Q

Heart

A

1% of total body weight ; can oxidise fatty acids and carbohydrates with 10% of resting metabolic rate

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7
Q

Liver

A

2.5% of total body weight ; 20% of resting metabolic rate - main glycogen store and source of blood glucose

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8
Q

Brain

A

Requires continuous supply of glucose and brain cannot metabolise fatty acids
Ketone bodies can partially substitute for glucose

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9
Q

Too little glucose

A

Hypoglycaemia - cause faintness and coma

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10
Q

Too much glucose

A

Hyperglycaemia can cause irreversible damage

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11
Q

ATP requirements

A

Light contraction - requirement met by OxPhos
Vigorous contraction - O2 limiting factor means glycogen breakdown in muscles and lactate formation

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12
Q

Heart

A

Must beat constantly and is designed for completely aerobic metabolism and rich in mitochondria ; heart utilises free fatty acids and ketone bodies

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13
Q

Loss of O2

A

Leads to cell death and myocardial infarction ; energy demand&raquo_space;> energy supply

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14
Q

Liver

A

Wide repertoire of metalolic processes - can interconvert nutrients ; glucose storage organ (glycogen)

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15
Q

Role of liver

A

Role in lipoprotein metabolism and transport of triglycerides/cholestrol

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16
Q

Excess glucose-6-phosphate

A

Can be used to generate glycogen in liver and muscle

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17
Q

Glucose 6 phosphate another fate

A

Via PPP makes nucleotides

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18
Q

Excess acetyl-CoA

A

Makes fatty acids and cholesterol

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19
Q

Fasting =

A

Ketone bodies

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20
Q

Extreme exercise

A

Demand outweighs supply and lactate is produced

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21
Q

To avoid hypoglycaemia

A

Breakdown liver glycogen stores
Release free fatty acids from adipose tissue
Convert acetyl CoA into ketone bodies

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22
Q

If all glycogen stores are used up

A

Gluconeogenesis

23
Q

TCA Cycle

A

OAA+Acetyl -> citrate
5c = a-ketoglutarate
4c = succinylcholine-CoA
Succinate
Fumarate
L-Malate (cycle begins again)

24
Q

Gluconeogenesis is

A

Pyruvate to Glucose C6

25
Q

When is lactate generated?

A

By skeletal muscle during strenuous exercise when rate of glycolysis exceeds rate of TCA cycle and electron transport chain (anaerobic respiration)

26
Q

What does lactate do?

A

Taken up by the liver and used to regenerate pyruvate by lactate dehydrogenase - Cori cycle

27
Q

Where do amino acids come from?

A

Diet or during starvation from breakdown of skeletal muscle

28
Q

Where does glycerol come from?

A

Triglyceride hydrolysis ; glycerol backbone is used to generate DHAP

29
Q

Pathway - gluconeogenesis

A

Pyruvate -> OAA -> Phosphoenol pyruvate (3C) -> G3P (+DHAP from glycerol) -> Fructose-1,6-bisphosphate -> Fructose-6-phosphate -> Glucose-6-phosphate (which creates glycogen when in excess) -> Glucose

30
Q

Gluconeogenesis

A

Key steps from
Pyruvate to OAA to Phosphoenolpyruvate

Fructose-1,6-bisphosphate to fructose-6-phosphate

G6P to Glucose

KEY STEPS MUST BE BYPASSED BY NON-GLYCOLYTIC PATHWAYS

31
Q

What is different about glycolysis and gluconeogenesis?

A

Overall delta G value for a straight reversal of glycolysis is +90kJ which is energetically unfavourable - SO MUST find a way to bypass those kinase driver reactions

32
Q

How to turn energetically unfavourable process into favourable one?

A

6 phosphoanhydride bonds are required

33
Q

4 extra enzymes gluconeognesis

A

Pyruvate to OAA (-2atp) - pyruvate carboxylase
OAA to phosphoenolpyruvate (-2gtp) phosphoenolpyruvate carboxykinase
Fructose-1,6-bisP to fructose-6-p ; fructose-1,6-bisphosphatase
Glucose-6-p to glucose ; glucose-6-phosphatase

34
Q

Delta g for gluconeogenesis

A

-38

35
Q

Glucogenic amino acids

A

Used to generate glucose via glucoseneogenesis

36
Q

Ketogenic amino acids

A

Used to synthesis fatty acids and ketone bodies

37
Q

Deamination of the 20 amino acids

A

Gives rise to 7 amino acids
OAA
FUMARATE
SUCCINATE
SUCCINYL-COA
PYRUVATE
ACETYL-COA
A-KETOGLUTARATE

38
Q

Fatty acids

A

CANNOT be converted into glucose via gluconeogensis but can be converted into ketone bodies to be used by muscle/brain

39
Q

When muscles contract

A

Demand for ATP increases so more glucose transporters
Adrenaline increases rate of glycolysis in the muscle and increasing rate of gluconeogenesis in the liver/release of fatty acids from adipocytes

40
Q

Anaerobic respiration

A

Lactate is produced by pyruvate (with H+ ion) in the muscle - passed into blood into liver and used in gluconeogenesis to synthesise more glucose

41
Q

What does lactate also do?

A

Replenishes NAD+ levels

42
Q

Michaelis constant

A

Concentration of substrate at which an enzyme functions at a half -maximal rate

43
Q

Control of metabolic pathways - muscle

A

Hk I is active at very low concentrations of glucose and very sensitive to G6P inhibition

44
Q

What does this mean in muscle?

A

Anaerobic conditions when rate of TCA drops and glycolysis slows ; hk1 is inhibited by accumulating levels of g6p

45
Q

Liver HK (iV)

A

has a much higher km so much lower glucose affinity and less sensitive to G6P inhibition

46
Q

gLUCOSE-6-PHOSPHATASE

A

Found in liver catalyses reverse reaction found in gluconeogenesis

47
Q

Glucocorticoids

A

Increase synthesis of metabolic enzymes concerned with glucose availability

48
Q

When fed

A

More glucose - more insulin - less glucagon
Glycolysis in liver produces acetyl coA which is broken down for fat synthesis
Also glycogen synthesis in muscle and liver
Overall stimulation of anabolic pathways

49
Q

Fasting states

A

Gluconeogenesis
glycogen breakdown
glucagon release
fatty acid breakdown for tap production (preserves glucose for brain)
adrenalin stimulates glycogen breakdown and glycolysis and lipolysis (adipose)

50
Q

Prolonged fasting

A

Adipose tissue hydrolyses triglyceride to provide fatty acids
TCA cycle intermediates reduced in amount to provide substrates for gluconeogenesis
pROTEIN BREAKDOWN provides amino acid substrates for gluconeogenesis
Ketone bodies produced from fatty acids/amino acids in liver to partially sub brain’s glucose requirement

51
Q

Type 1

A

failure to secrete enough insulin

52
Q

type 2

A

failure to respond appropriately to insulin

53
Q

4 complications of diabetes

A

Hypo/hyperglycaemia
cardiovascular complications
ketoacidosis

54
Q

Atherosclerosis

A

Buildup of fatty acids/cholestrol