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Integration Of Metabolism Flashcards

1
Q

What molecules does the brain metabolise?

A

Only glucose Although ketone bodies can partially substitute the need for glucose

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2
Q

What is too much and too little glucose called?

A

Hypoglycaemia Faintness Coma Hyperglycaemia Irreversible tissue damage

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3
Q

What percent of our total body weight is skeletal muscle?

A

40%

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4
Q

what happens during the light contraction of skeletal muscle?

A

ATP requirements are met by oxidative phosphorylation Oxygen, glucose and fatty acids are used as fuel

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5
Q

What happens during vigorous contraction of skeletal muscle?

A

ATP consumption is faster than supply by OxPhos Oxygen becomes a limiting factor Glycogen is broken down Pyrivate is converted to lactate

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6
Q

How is the heart adapted for constant beating?

A

Designed for completely aerobic metabolism Rich in mitochondria Not fussy: Readily uses TCA cycle substrates (fatty acids, ketone bodies) and feeds these into the cycle

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7
Q

What happens then there is lots of oxygen flow to the heart?

A

Deveatating Cell death Myocardial infarction Energy demand >>> energy supply

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8
Q

What is the metabolism of the liver like?

A

Wide repertoire of metabolic processes Highly metabolically active Can inter convert nutrient types Plays a central role in maintaining blood [glycose] at 4.0-5.5 mM Glucose storage organ (glycogen) Plays a key role in lipoprotein metabolism

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9
Q

What does the skeletal muscle metabolise?

A

Carbohydrates and fatty acids

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10
Q

What does the brain metabolise?

A

2% of body weight but uses 20% of the metabolism Can’t metabolise fatty acids

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11
Q

What is the role of adipose tissue in metabolism?

A

Storage of fatty acids in the form of triglycerides

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12
Q

What does the heart metabolise?

A

1% of body weight, 10% of metabolic rate Fatty acids and carbohydrate

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13
Q

During glycolysis, what is doe with excess glucose-6-phosphate?

A

Used to generate glucogen

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14
Q

What is excess acetyl CoA used for?

A

Generating fatty acids

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15
Q

What happens to acetyl CoA during fasting?

A

Ketone body production (Instead of fatty acid

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16
Q

What happens to glucose-6-phosphate via the pentose phosphate pathway?

A

Source for nucleotide production in a pathway that generates the bulk of NADPH needed for anabolic pathways e.g. cholesterol synthesis

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17
Q

What can the body do to avoid hypoglycaemia?

A

Breakdown liver glycogen stores Release free fatty acids from adipose tissue Convert Acetyl CoA into ketone bodies via the liver Fatty acids and ketone bodies can both be used by the muscle, making more glucose available for the brain

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18
Q

How long will glycogen stores last when there is no glucose? What is needed to combat this?

A

12-18 hours gluconeogenesis

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19
Q

What is the overall aim of gluconeogenesis?

A

To make glucose from pyruvate

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20
Q

What are the steps in gluconeogenesis

A

PoM 2.6 part 5 please learn

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21
Q

Where do non carbohydrate precursors enter the gluconeogenesis pathway, and what molecules?

A

Lactate - enters at pyruvate Amino acids - pyruvate and oxaloacetate Glycerol - at DHAP (C3)

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22
Q

What happens to the lactate produced by skeletal muscles?

A

Taken up by the liver and utilised to regenerate pyruvate b lactate dehydrogenase (LDH)

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23
Q

What is the glycerol backbone of hydrolysed fatty acids used for?

A

Either generate dihydroxyacetone phosphate (DHAP) for step 5 of glycolysis

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24
Q

Glycolysis involves three reactions which are asesntiall irreversible, what are these?

A

Glucose —>glucose-6-phosphate Using hexokinase Fructose-6-p —>fructose-1,6-BisP Using phosphofructokinase Phosphoenolpyruvate —> pyruvate Using oyruvate kinase

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25
How is gluconeogenesis made into a energetically favourable reaction?
Using 4 extra enzymes: Pyruvate carboxylase Phosphoenolpyruvate carboxykinase Fructose-1,6-bisphosphatase Glucose-6-phosphatase DG for straight reversal of glycolysis would be +90 With the enzymes it is -38
26
Deamination of all 20 amino acids gives rise to just 7 molecules, what are these?
Pyruvate Acetyl CoA Acetoacetyl CoA A-ketoglutarate Succinyl CoA Fumarate Oxaloacetate Urea is lost as a waste product
27
What are glucogenic and ketogenic amino acids?
Glucogenic Their skeletons can give rise to glucose via gluconeogenesis Ketogenic Give rise to skeletons which can’t can’t enters gluconeogenesis but can be used to synthesise fatty acids and ketone bodies
28
What happens when 2C atoms enter the TCA cycle?
They enter as acetyl CoA Join with oxaloacetate to form citrate Eventually the two carbons are lost as CO2 Oxaloacetate is regenerated So no net synthesis of pyruvate or oxaloacetate
29
During exercise with adequate oxygen supply (aerobic) how are ATP demands met?
Glucose transported from blood to muscle cells Undergoes metabolism buy glycolysis and TCA cycle and oxidative phosphorylation Fatty acids also enter this process
30
How is increased demand for glucose from muscle cells met?
Increase in the number of glucose transporters on the membranes of muscle cells
31
What roles does adrenaline play in meeting the demand for ATP?
Increasing the rate of glycolysis in muscle cells Increasing the rate of gluconeogenesis Increasing the release of fatty acids from adipocytes
32
What happens when ATP and glucose demands can’t be me and anaerobic conditions take over?
Glycogen in the muscle is broken down To replenish NAD+ to maintain glycolysis, pyrivate is converted to lactate in the liver using LDH Lactate can then be used by the liver to generate glucose by gluconeogenesis
33
What is control of metabolic reactions usually centered around?
Irreversible steps. Usually early on Increased rate of these enzyme activity greatly increases the rate of downstream steps
34
What is the km (michaelis constant) ?
Concentration of a substrate at which an enzyme works at half-maximal rate (Vmax)
35
Which forms of hexokinase do muscle and liver contain and what are some properties of this enzyme in each place?
Muscle: Hexokinase I High glucose affinity (Km of 0.1 mM) Highly sensitive to G-6-P inhibition Liver: Hexokinase IV Low glucose affinity (Km of 4 mM) Less sensitive to G-6-P inhibition
36
What does the low Km of hexokinase I mean?
In the muscle HK is active at very low glucose concentrations. As it is sensitive to G6P inhibition this means that under anaerobic condition when the TCA cycle stops and glycolysis slows HK I is inhibited by high levels of G6P
37
What is glucose 6-phosphates and where is it found?
In the liver Reverse of hexokinase Generates glucose from G6P
38
What is the role of insulin?
Secreted from islet cells in the pancreas Secreted when blood glucose levels rise, stimulating uptake and use of glucose. And storage as glycogen and fat
39
What is the result of glucagon?
Secreted from islets in the pancreas Secreted when blood glucose drops, stimulates the production of glucose through gluconeogenesis and the breakdown of glycogen (glycogenolysis) and fat
40
What is the role of adrenaline with regards to glucose?
Strong and fast metabolic affect to mobilise glucose for fight or flight
41
What do glucocorticoids do?
Steroid hormones Increase synthesis of metabolic enzymes concerned with glucose availability
42
What happens when glucose levels rise after a meal?
Increased insulin Decreased glucagon Increased glucose uptake by liver, used for glycogen synthesis and glycolysis (Acetly CoA produced is used for fatty acid synthesis) Increased glucose uptake and glycogen synthesis in muscle Increased triglyceride synthesis in adipose Increased use of metabolic intermediates for synthesis and growth
43
What happens when blood glucose starts to fall?
Increased glucagon Decreased insulin Glucose production in liver from glycogen breakdown and gluconeogenesis Utilisation of fatty acid breakdown as an alternative substrate ( saves glucose for brain) Adrenalin also has similar effects on the liver As well as stimulating glycogen break down in muscle and glycolysis, and adipose tissue towards fat lipolysis as another alternate substrate
44
What happens after prolonged fasting (glycogen stores used up)?
Glucagon/insulin ratio increases Adipose tissue hydrolyses triglycerides to provide fatty acids TCA cycle intermediated are reduced in amount to provide substrate for gluconeogenesis Protein breakdown provides amino acid substrates for gluconeogenesis Ketone bodies are produces from fatty acids and amino acids in the liver to partially substitute the Brains glucose requirement
45
What are the two main types of diabetes mellitus?
Type I Can’t secrete enough insulin (B cell dysfunction) Type II Individuals can’t respond to insulin (insulin resistance) The result of both is that the body acts as though it is always fasting
46
What are some complications of diabetes?
Hyperglycaemia with progressive tissue damage Increase in plasma fatty acid and lipoprotein levels with possible cardiovascular complications Increase in ketone bodies, with risk of acidosis Hypoglycaemia with consequent coma if insulin dosage is imperfectly controlled
47
What happens with respect to glucagon in people with diabetes?
Glucagon stimulates gluconeogenesis and glycongenolysis Insulin deficiency and relative excess of glucagon leads to increased hepatic output of a glucose, and thus hyperglycaemia
48
What are the steps in gluconeogenesis
PoM 2.6 part 5 please learn
49
Where do non carbohydrate precursors enter the gluconeogenesis pathway, and what molecules?
Lactate - enters at pyruvate Amino acids - pyruvate and oxaloacetate Glycerol - at DHAP (C3)
50
What happens to the lactate produced by skeletal muscles?
Taken up by the liver and utilised to regenerate pyruvate b lactate dehydrogenase (LDH)
51
What is the glycerol backbone of hydrolysed fatty acids used for?
Either generate dihydroxyacetone phosphate (DHAP) for step 5 of glycolysis
52
Glycolysis involves three reactions which are asesntiall irreversible, what are these?
Glucose —\>glucose-6-phosphate Using hexokinase Fructose-6-p —\>fructose-1,6-BisP Using phosphofructokinase Phosphoenolpyruvate —\> pyruvate Using oyruvate kinase
53
How is gluconeogenesis made into a energetically favourable reaction?
Using 4 extra enzymes: Pyruvate carboxylase Phosphoenolpyruvate carboxykinase Fructose-1,6-bisphosphatase Glucose-6-phosphatase DG for straight reversal of glycolysis would be +90 With the enzymes it is -38
54
Deamination of all 20 amino acids gives rise to just 7 molecules, what are these?
Pyruvate Acetyl CoA Acetoacetyl CoA A-ketoglutarate Succinyl CoA Fumarate Oxaloacetate Urea is lost as a waste product
55
What are glucogenic and ketogenic amino acids?
Glucogenic Their skeletons can give rise to glucose via gluconeogenesis Ketogenic Give rise to skeletons which can’t can’t enters gluconeogenesis but can be used to synthesise fatty acids and ketone bodies
56
What happens when 2C atoms enter the TCA cycle?
They enter as acetyl CoA Join with oxaloacetate to form citrate Eventually the two carbons are lost as CO2 Oxaloacetate is regenerated So no net synthesis of pyruvate or oxaloacetate
57
During exercise with adequate oxygen supply (aerobic) how are ATP demands met?
Glucose transported from blood to muscle cells Undergoes metabolism buy glycolysis and TCA cycle and oxidative phosphorylation Fatty acids also enter this process
58
How is increased demand for glucose from muscle cells met?
Increase in the number of glucose transporters on the membranes of muscle cells
59
What roles does adrenaline play in meeting the demand for ATP?
Increasing the rate of glycolysis in muscle cells Increasing the rate of gluconeogenesis Increasing the release of fatty acids from adipocytes
60
What happens when ATP and glucose demands can’t be me and anaerobic conditions take over?
Glycogen in the muscle is broken down To replenish NAD+ to maintain glycolysis, pyrivate is converted to lactate in the liver using LDH Lactate can then be used by the liver to generate glucose by gluconeogenesis
61
what are the steps in gluconeogenesis?

Lily PoM MBC (15 decks)

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