Lecture 34 - Coordinating Metabolism: Starvation

Question 1

What are key concepts of energy homeostasis under starvation?

Answer 1

• Maintenance of blood glucose for brain function
• Less glucose use in multiple tissues
• Alternative fuels
• Provision of special fuel needs of each tissue
• Sparing of structural body proteins

Question 2

How much glycogen is stored in the liver?

Answer 2

~100 g

Question 3

How much glucose does the brain need per day?

Answer 3

~120 g

Question 4

How much energy is stored in 15 kg’s of TAG?

Answer 4

590000kJ

Question 5

How many days could you survive for using only energy from TAG assuming 10000kJ per day?

Answer 5

59 days

Question 6

What happened to the subjects in the Minnesota starvation experiment (1944)?

Answer 6

The men lost fat and muscle, were tired and became very irritable but recovered on refeeding.

Question 7

What was the Minnesota starvation experiment (1944)?

Answer 7

Study conducted by Dr Ancel Keys on 36 men to study the physiological effect of starvation i.e.calorie intake halved for 6 months

Question 8

What happens to fuel levels in blood during starvation?

Answer 8

• Ketone production ramped up
• Glucose levels maintained
• Increase in FFAs
• Protein utilised initially then conserved

Question 9

What can the brain utilise as an alternative to glucose?

Answer 9

Ketone bodies

Question 10

Origin of blood glucose stage I of fed to starving?

Answer 10

Exogenous

Question 11

Origin of blood glucose stage II of fed to starving?

Answer 11

Glycogen, Hepatic gluco-neogenesis

Question 12

Origin of blood glucose stage III of fed to starving?

Answer 12

Hepatic gluconeogenesis, Glycogen

Question 13

Origin of blood glucose stage IV of fed to starving?

Answer 13

Gluconeogenesis hepatic and renal

Question 14

Origin of blood glucose stage V of fed to starving?

Answer 14

Gluconeogenesis hepatic and renal

Question 15

In which stages of from fed to starving is glucose the major fuel of the brain?

Answer 15

Stage I - Stage III

Question 16

What are the major fuels of the brain in stage IV and V?

Answer 16

Ketone bodies + Glucose

Question 17

What tissues are using glucose in stage I of fed to starving?

Answer 17

All

Question 18

What tissues are using glucose in stage II of fed to starving?

Answer 18

All except - liver, muscle and adipose at diminished rates

Question 19

What tissues are using glucose in stage III of fed to starving?

Answer 19

All except liver, muscle and adipose tissue at rates intermediate between II and IV

Question 20

What tissues are using glucose in stage IV of fed to starving?

Answer 20

Brain, RBCs, renal medulla, small amount by muscle

Question 21

What tissues are using glucose in stage V of fed to starving?

Answer 21

Brain at diminished rate, RBCs, Renal medulla

Question 22

What can new glucose be made from in the liver?

Answer 22

Gluconeogenic precursors

Question 23

What does mobilisation of fat from adipose do?

Answer 23

Creates an influx of FFAs into the liver

Question 24

What does an influx of FFAs into the liver cause?

Answer 24

B-oxidation which increases
acetyl CoA which
drives ketogenesis.

Question 25

What do ketone bodies provide?

Answer 25

Acetyl CoA for TCA cycle and ATP generation in brain and muscle.

Question 26

What drives the intertissue relationships during starvation?

Answer 26

Glucagon in response to low glucose and potentiated by cortisol and adrenaline

Question 27

What happens in the starvation metabolism?

Answer 27

- Gluconeogenesis in 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.

Question 28

What hormone activates gluconeogenesis?

Answer 28

Glucagon

Question 29

What is FoxO1?

Answer 29

A transcription factor that activates gluconeogenic genes.

Question 30

Are are some enzymatic reactions in metabolism reversible?

Answer 30

Yes many

Question 31

Are reversible enzymatic reactions catalysed by the same enzyme?

Answer 31

Sometimes, however some enzymes require different enzymes to go in one direction or the other

Question 32

Where does gluconeogenesis mainly occur?

Answer 32

The liver, some in kidney

Question 33

What can glucose be synthesised from in gluconeogenesis?

Answer 33

– lactate from Rbcs and muscle – alanine from muscle protein – glycerol from adipose tissue

Question 34

What provides the energy + reducing power for gluconeogenesis?

Answer 34

Fatty acid oxidation

Question 35

What uses most of the glucose from gluconeogenesis?

Answer 35

The brain

Question 36

What does alcohol inhibit?

Answer 36

Gluconeogenesis

Question 37

How many molecules of NADH are produced for every molecule of alcohol metabolized?

Answer 37

Two molecules of NADH.

Question 38

What effect does alcohol have on the NADH/NAD+ ratio?

Answer 38

It increases the NADH to NAD+ ratio.

Question 39

Which gluconeogenic precursors are driven away from gluconeogenesis due to high NADH levels?

Answer 39

- Pyruvate is converted to lactate. - Oxaloacetate is converted to malate.

Question 40

What are the consequences of alcohol inhibiting gluconeogenesis?

Answer 40

It lowers blood glucose, lowers pH, and can lead to coma.

Question 41

Why should you avoid drinking alcohol, especially in starvation mode?

Answer 41

Drinking alcohol in starvation mode can inhibit gluconeogenesis, leading to low blood glucose and impaired brain function.

Question 42

How are ketone bodies synthesised?

Answer 42

In the liver from fatty acids

Question 43

What does a starving brain use as an energy source?

Answer 43

Ketone bodies

Question 44

Ketone body concentrations in the fed state?

Answer 44

< 0.1 mmol/L

Question 45

Ketone body concentration in fasted state?

Answer 45

0.3 mmol/L

Question 46

Ketone body concentration in starved state?

Answer 46

10 mmol/L

Question 47

Type 1 diabetes ketoacidosis ketone body concentration?

Answer 47

> 30 mmol/L