2.7 Integration Of Metabolism Flashcards

1
Q

What forms of energy production does skeletal muscle rely on?

A

Fatty acid oxidation and carbohydrate oxidation

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2
Q

During light contraction of skeletal muscle, how is ATP consumption met?

A

Through oxidative phosphorlyation

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3
Q

During vigorous contraction, how is ATP consumption met?

A

Muscle stores of glycogen are then broken down to produce ATP

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4
Q

Under anaerobic conditions, what is pyruvate converted into?

A

Lactate

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5
Q

What is the only substrate that the brain can use as a source of energy?

A

Glucose/carbohydrates

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6
Q

Which energy source can the brain not use?

A

The brain cannot metabolise fatty acids

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7
Q

What can partially substitute for glucose in the brain?

A

Ketone bodies

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8
Q

What can too little glucose in the brain cause?

A

Hypoglycaemia - faintness and coma

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9
Q

What can too much glucose in the brain cause?

A

Hyperglycaemia - irreversible damage to multiple organ systems like retinas

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10
Q

What does the heart utilise for energy substrates?

A

TCA cycle substrates – free fatty acids and ketone bodies

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11
Q

What happens to the heart when energy demand > energy supply?

A

Myocardial infarction

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12
Q

Name four fuel sources for the heart

A

Ketone bodies, glucose, fatty acids and lactate

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13
Q

Why does the heart have a lot of mitochondria?

A

Because the heart is designed for aerobic conditions – high energy supply

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14
Q

How does the liver store glucose?

A

As glycogen

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15
Q

What range does the liver try keep the blood glucose levels between?

A

4-5.5 mmol/L

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16
Q

Excess of what can be used to generate glycogen in the liver and muscle?

A

Excess glucose-6-phosphate

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17
Q

How are fatty acids stored in adipose tissue?

A

They are stored as triglycerides in the adipose tissue

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18
Q

During fasting, what happens to the Acetyl CoA which is produced?

A

Much of the Acetyl CoA is used to generate ketone bodies

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19
Q

What happens to lactate production during periods of intense exercise?

A

It increases - produced from pyruvate

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20
Q

What three things can the body initially do when the blood glucose concentration drops below 3mM?

A
  • Breakdown liver glycogen stores to maintain levels
  • Release free fatty acids from adipose tissue
  • Convert Acetyl CoA into ketone bodies in the liver
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21
Q

How does the brain get more glucose when the body is in a hypoglycaemic coma?

A

The skeletal muscle can use ketone bodies and fatty acids

This makes more plasma glucose available for the brain which cannot metabolise fatty acids

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22
Q

After how many hours are the bodies glycogen stores depelated?

A

12-18 hours

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23
Q

After the body has depleted its glycogen stores, what is used to generate glucose?

A

Gluconeogenesis

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24
Q

How is pyruvate regenerated from lactate?

A

Using lactate dehydrogenase enzyme

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25
Which reaction in gluconeogenesis occurs in the mitochondria?
The convertion of pyruvate to oxaloacetate
26
What enzyme is used to convert pyruvate into oxaloacetate?
Pyruvate carboxylase
27
How does oxaloacetate move out the mitochondria once it has been produced from pyruvate?
It moves via the **malate shuttle**, where it is then converted into phosphophenolpyruvate
28
How do glucogenic amino acids give rise to glucose?
They undergo **deamination** reactions which results in the production of **pyruvate**, which yields glucose through gluconeogenesis
29
Where do the reactions of gluconeogenesis occur?
Pyruvate to oxaloacetate in mitochondria Rest in cytosol
30
List out all the reactions in gluconeogenesis
**Pyruvate** **Oxaloacetate** by pyruvate carboxylase **Phosphoenolpyruvate** by phosphoenolpyruvate carboxykinase **F-1,6-BP** **F6P** by fructose-1,6-bisphosphatase **G6P** **Glucose** by glucose-6-phosphatase
31
How is gluconeogenesis made energetically favourable?
The 4 additional high energy bonds make it energetically favourable ΔG for the straight reversal of glycolysis would be +90 (unfavourable) but ΔG for gluconeogenesis is -38 kJ/mol
32
What do ketogenic amino acids give rise to?
Skeletons that can be used to synthesise FAs and ketone bodies but **cannot enter gluconeogenesis**
33
What happens to pyruvate during anaerobic respiration?
It is taken up by the liver and converted into lactate by LD to replenish NAD+ levels and maintain glycolysis
34
In the fasting state, what is the main metabolic fuel for the heart?
Fatty acids
35
In the fasting state, what is the main metabolic fuel for the brain?
Glucose
36
In the fed state, why does insulin stimulate an increase in the number of glucose transporters on the adipocyte surface?
To facilitate glucose uptake to make triglycerides
37
Why do plasma levels of ketone bodies increase as the fed state progresses into fasting and then starvation?
Ketone bodies are produced by the liver
38
How can glucogenic amino acids be used as a fuel source?
The glucogenic amino acids' skeletons can give rise to glucose via gluconeogenesis
39
In the fasting state, glucagon acts to increase the synthesis of glucose from which molecules?
Glycogen, glycerol and amino acids
40
What generates the bulk of the NADPH needed for anabolic pathways e.g. cholesterol synthesis?
Glucose-6-phosphate via the pentose phosphate pathway
41
What are three non-carbohydrate precursors which enter into the gluconeogenic cycle?
Lactate, amino acids and glycerol
42
What is the cori cycle?
The generation of pyruvate from lactate
43
How does glycerol act as a non-carbohydrtae substrate for gluconeogenesis?
It is used to produced DHAP and enter the gluconeogenic pathway
44
Which are the three reactions of gluconeogenesis which need to be bypassed through using kinase enzymes?
Phosphenolpyruvate to pyruvate Fructose - 1,6 - Bisphosphate to Fructose - 6 - Phosphate Glucose - 6 - Phosphate to Glucose
45
What enzyme is used to convert Glucose - 6 - Phosphate into Glucose?
Glucose - 6 - Phosphatase
46
What organs is Glucose - 6 - Phosphatase found in?
Liver and kidneys
47
What are the seven molecules which deamination of all 20 amino acids gives rise to?
``` Pyruvate Oxaloacetate Succinyl CoA Fumerate Acetyl CoA Acetoacetyl CoA Alpha-ketoglutarate ```
48
What happens to the rest of the amino acid once it has been broken down by deamination?
Remaining compounds are excreted in the urea
49
Which tissues can use ketone bodies as an energy source?
Muscle and brain
50
What happens to the glucose transporters on the membranes of muscle cells as the muscle contracts?
The number present on the membranes of the muscle cells increases
51
What three effects does adrenaline have on helping the cell meet the adequate demands for ATP?
Increases the rate of **glycolysis in muscle** increases th rate of **gluconeogenesis in liver** Increases the release of **fatty acids from adipocytes**
52
What causes an increase in muscle glycolysis, gluconeogenesis and fatty acid breakdown during exercise?
The release of adrenaline
53
During anaerobic conditions what happens to the glycogen in the muscle?
It is broken down
54
What is the name of the pathway given to the breakdown of glycogen into glucose?
Glycogenolysis
55
What triggers glycogenolysis?
Glucagon
56
How is the Cori cycle used in anaerobic conditions?
Pyruvate is taken up by the liver and converted into lactate using **lactate dehydrogenase** The replenished NAD+ levels allows glycolysis to continually occur
57
What does insulin do?
Stimulates the uptake and use of glucose, and storage of glycogen and fat
58
What enzymes catalyses the first, irreversible step of glycolysis?
Hexokinase
59
What are the two different isoforms of hexokinase found in the muscle and the liver?
Hexokinase I is found in muscle Hexokinase IV is found in the liver
60
What is the Michaelis constant?
The **concentration of substrate** at which an enzyme functions at **half-maximal rate** (Vmax)
61
What is the Km of Hexokinase I and what does it mean?
0.1 mM This means it is **active** at very **low concentrations of glucose** and thus operates at maximum velocity at all times
62
Which hexokinase is sensitive to inhibition by product glucose - 6 - phosphate?
Hexokinase I
63
What are the four changes which occur during aerobic exercise?
1. Increase in **number of glucose transporters** in muscle 2. Increase **glycolysis** in muscle 3. Increase **gluconeogenesis** in liver 4. Increased **beta oxidation** to make Acetyl CoA which is the used to generate ATP
64
Where does the convertion of lactate into pyruvate occur?
IN the liver
65
During the fasted state, the transamination reactions of amino acid are an important substrate for what process?
Gluconeogenesis
66
During anaerobic conditions, why is hexokinase I Inhibited?
During anaerobic conditions, glycolysis slows Glucose concentration drops but hexokinase I is still active because of its low Km, thus glucose is converted into G6P Thus G6P accumulates which inhibits hexokinase I
67
Where is Hexokinase IV found?
In the liver
68
What does Hexokinase IV do?
Converts glucose into glucose-6-phosphate in the liver
69
What is the KM of Hexokinase IV?
4
70
What does the KM value of Hexokinase IV indicate?
4 - only active at very high concentrations of glucose
71
Which hexokinase enzyme is more sensitive to G-6-P inhibition?
Hexokinase I
72
What occurs straight after a meal has been consumed?
Insulin is secreted and glucagon drops, causing: * increased glucose uptake by liver for **glycogenesis** and **glycolysis** where **acetyl CoA** produced is used for **lipogenesis** * increased glucose uptake and glycogenesis in muscle * increased triglyceride synthesis in adipose tissue * increased metabolic intermediate usage
73
What happens after a period of fasting following a meal?
Glucose has been all stored as glycogen so blood glucose levels start to drop - This triggers glucagon secretion - Glucagon triggers glycogenolysis, and gluconeogenesis - Beta oxidation occurs – fatty acids become an alternative substrate for ATP to **preserve glucose for the brain**
74
What happens after prolonged fasting?
- Glycogen stores have all been used up, so **gluconeogenesis** dominates - Proteolysis also occurs to make amino acids that can undergo deamination reactions to make pyruvate - used in gluconeogenesis
75
Why does triglyceride hydrolysis increase during periods of prolonged fasting?
The triglycerides are broken down into glycogen and fatty acids **Fatty acids** used in **beta-oxidation** to make ATP substrates (acetyl CoA) **Glycogen** can assist with gluconeogenesis, enters as **DHAP**
76
Why does ketone body synthesis occur during periods of prolonged fasting?
During fasting, gluconeogenesis is occuring This means all **oxaloacetate** is being **used up** Therefore, there may be an **excess of Acetyl CoA** The **excess Acetyl CoA** is used to produce **ketone bodies** through ketogenesis
77
How does diabetic ketoacidosis occur?
The body does **not produce enough insulin**, therefore glucose cannot be stored in cells, body **relies on fats for energy** Fatty acids are broken down into **ketone bodies**
78
What happens to the insulin : glucagon ration after periods of prolonged fasting?
Increases further
79
Which cells of the islets is glucagon released from?
Alpha cells
80
What two processes does glucagon stimulate in the liver?
Glycogenolysis and gluconeogenesis
81
What are glucocorticoids?
Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability
82
Wh are ketone bodies produced after periods of prolonged fasting?
Ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose