Late Starvation

Question 1

What is the only source of de novo gluconeogenesis? How much of this can we get?

Answer 1

Glycerol from lipolysis. 30g glucose from glycerol per day.

Question 2

What happens after a few hours of blood glucose concentration being below 5mM?

Answer 2

Insulin secretion stops which stimulated lipolysis.

Question 3

What does hypoinsulinemia lead to?

Answer 3

Proteolysis - release of amino acids from tissues (mainly muscle).

Question 4

Amino acid ______ are used for gluconeogenesis.

Answer 4

Carbon skeletons.

Question 5

Amino acids need to get to the ______. Need to do something with the poisonous ______.

Answer 5

Liver. Amine groups (ammonia).

Question 6

What are amine groups channelled into in the processing of amino acids?

Answer 6

Into three amino acids - Alanine, glutamate and aspartate.

Question 7

What is the amino acid reacting within the processing of amino acids? What does the reaction do?

Answer 7

Alpha-ketogluterate (pyruvate, 2-oxoglutarate and oxaloacetate). Strips the amino acid of its amine group, turning it into an alpha-keto acid. These can go into gluconeogenesis.

Question 8

The amino group has to be transferred into something that can be removed by the body. How is this done?

Answer 8

Urea cycle.

Question 9

Where does the urea cycle occur?

Answer 9

Only in the liver.

Question 10

How does the urea cycle work?

Answer 10

Amine groups (NH2) are channelled into urea synthesised by aspartate and glutamate.

Question 11

What is gluconeogensis?

Answer 11

Making glucose from other things (mainly pyruvate)

Question 12

What are the three rate-limiting steps that need to be bypassed in gluconeogenesis?

Answer 12

Hexokinase (glucose trapping step)
Phosphofructokinase (rate limiting step
Pyruvate (Final energy releasing step)

Question 13

Why is gluconeogenesis only done in the liver? Where in the liver is most of the process performed and what is the exception to this?

Answer 13

It is the only place in the body that can bypass the three steps. Cytoplasm. Pyruvate carboxylase in the mitochondria (first step).

Question 14

What are the substrates used in gluconeogenesis?

Answer 14

Lactate - easily made into pyruvate
Glycerol
Amino acid carbon skeletons

Question 15

Where does lactate enter the gluconeogenesis process?

Answer 15

Enters as pyruvate in the first step

Question 16

Where does glycerol enter gluconeogenesis, how?

Answer 16

In the middle of the cycle. Turned into glycerol phosphate by glycerol kinase, then to dihydroxyacetone phosphate by glycerol phosphate dehydrogenase. which can go to glucose.

Question 17

How do amino acid carbon skeletons enter gluconeogenesis?

Answer 17

Via Krebs cycle intermediates. Oxaloacetate to pyruvate. Some to acetyl CoA and cant go to gluconeogenesis.

Question 18

What are some reasons why we need to reduce glucose consumption of the brain in starvation?

Answer 18

Cant just use all the amino acids, they do important jobs, not all aa can turn into glucose and it takes a lot of ATP to dispose of the amine groups.

Question 19

After how long starvation will lipolysis be at maximum? What does this mean?

Answer 19

2-3 days. FA released into bloodstream increased, more FA than is needed as cells don’t need to use this much.

Question 20

What is unique about beta-oxidation in the liver?

Answer 20

It can do beta-oxidation without the need for ATP demand. CoA can be regenerated from acetyl-CoA in a pathway other than the Krebs cycle.

Question 21

What is the ketone body formation pathway?

Answer 21

In the liver - starts with 2 acetyl-CoA to acetoacetyl-CoA to HMG-CoA to acetoacetate (4 carbon).

Question 22

What is acetoacetate? Why is the benefit of this being made by the liver?

Answer 22

Very good at being oxidised and taken up into cells. 2 acetyl CoA molecules go in and CoA has been regenerated which allows beta oxidation to go in absence of krebs cycle demand. Disposes of fatty acids.

Question 23

What happens to acetoacetate?

Answer 23

Interconversion to beta-hydroxybutyrate - both can be taken into tissues including the brain. It can be split in mitochondria to acetyl-CoA to fuel Krebs cycle and inhibit PDH.

Question 24

What does uptake of acetoacetate by the brain mean for the body?

Answer 24

Relieved use of glucose by the brain to 30g/day.

Question 25

Why can ketone body metabolism be inefficient?

Answer 25

Ketone bodies will be lost in the urine and they can spontaneously decarboxylate into acetone which is a waste product.

Question 26

What eventually kills us if we are in starvation?

Answer 26

Protein loss from all the tissues as the brain still needs glucose and some other tissues as well do we will always break down some protein.