T2 L5 The liver & glucose homeostasis

Question 1

What are the functions of the liver?

Answer 1

1) Stores glycogen from ingested carbohydrates & other non carbohydrate precursors
2) Breaks down glycogen & release glucose when plasma glucose levels fall
3) Synthesises glucose from non-carbohydrate precursors for release to maintain plasma glucose
4) Synthesises ketone bodies & secretes them into the blood as fuel for other tissues
5) Deaminates surplus amino acids & converts the amino groups & ammonia to urea
6) Aids in elimination of cholesterol from the body & synthesises bile salts from cholesterol
7) Acts as storage depot for fat soluble vitamins
8) Major site for metabolism & elimination of drugs & toxic substances

Question 2

What 3 body fuels are oxidised for ATP synthesis?

Answer 2

Glucose - stored as glycogen
Long chain fatty acids - stored as triacylglycerol
Amino acids - mainly present in proteins

Question 3

What are the phases of assimilation?

Answer 3

1) Immediate absorptive events

2) Post absorptive events

Question 4

What happens in the immediate absorptive events after a meal?

Answer 4

Immediate fate of dietary compounds
Liver & adipose tissue mainly take up materials = import
Some amino acids are used to synthesise proteins & some fat is used to synthesis membrane fats

Question 5

What happens in the post-absorptive events after a meal?

Answer 5

Between meals the cells of the liver & adipose tissue export
Body must cope with decreased availability of metabolites in the blood, which requires metabolism of the reserves of glycogen built up during feeding

Question 6

Why is the brain vulnerable to hypoglycaemia?

Answer 6

The cerebral cells mainly derive their energy from aerobic metabolism of glucose

Question 7

What can’t cerebral cells do?

Answer 7

Store glucose in significant amounts
Synthesise glucose
Metabolise substrates other than glucose or ketone bodies
Extract sufficient glucose for their needs from the extracellular fluid at low concentrations as glucose entry into the brain is not facilitated by hormones.

Question 8

What is gluconeogenesis?

Answer 8

Glucose synthesis in the liver & kidneys from non-carbohydrate precursors such as amino acids, glycerol & lactate

Question 9

What is glycolysis?

Answer 9

Oxidation of glucose by peripheral tissues

Question 10

What is glycogenolysis

Answer 10

Mobilisation of glycogen stores in the liver

Question 11

What does insulin do?

Answer 11

Increase glycolysis, glycogen & fat synthesis

Question 12

What do glucagon, catecholamines, cortisol & growth hormone do to gluconeogeneis & glycogenolysis?

Answer 12

They increase it

Question 13

How is glucose controlled via hormones?

Answer 13

Blood glucose doesn’t vary much throughout the day or night
Mainly controlled by fluctuations in circulating levels of insulin & glucagon
Alterations in the ratio of insulin: glucagon within the blood are essential for the maintenance of blood glucose

Question 14

How long is glucose absorbed for after a meal?

Answer 14

2-3 hours from the small intestine

Glycogen is degraded between meals & stores last for 12-24 hours

Question 15

What is the most important metabolic effect of insulin?

Answer 15

It stimulates the entry of glucose into cells

Transport of molecules can be passive or active

Question 16

What are gluts?

Answer 16

A family of glucose transporter proteins that transport glucose into the cell.

Question 17

What is glut 1?

Answer 17

Found in many tissues - erythrocytes, muscle, brain, kidney, colon, placenta, foetal tissue
Responsible for basal glucose uptake in most tissues
Increased in amount by glucose deprivation
Affinity is around 1mM

Question 18

What is glut 2?

Answer 18

Found in liver, pancreatic beta cells, kidney & small intestine
High capacity
Low affinity at around 15-20mM
Only takes up glucose at high plasma conservation which conserves it for other tissues such as the brain

Question 19

What is glut 3?

Answer 19

Found in the brain & is predominantly neuronal
Supplements glut in tissue with high energy demands
High affinity of 1mM which allows glucose uptake, irrespective of blood glucose concentration

Question 20

What is glut 4?

Answer 20

Found in skeletal muscle, heart & adipose tissue (insulin-sensitive)
Insulin sensitive transporter
Affinity around 5mM so controlled by plasma glucose levels & number of transporters on the membrane
Lives in cytoskeleton of the cell & is only inserted into the membrane under the influence of insulin.

Question 21

What is glut 5?

Answer 21

Found in the small intestine

Fructose transporter

Question 22

Why does the liver only take up glucose when there is a high concentration?

Answer 22

To save glucose for the other organs

Question 23

What are the immediate cellular effects of insulin?

Answer 23

Increases rate of glucose uptake in muscle & adipocytes
Modulation of the activity of enzymes involved in glucose metabolism
Occurs in minutes
Doesn’t require protein synthesis

Question 24

What are the longer-lasting cellular effects of insulin?

Answer 24

Results from continued exposure to insulin
Increase expression of liver enzymes that synthesise glycogen
Increase expression of adipocyte enzymes that synthesise triacylglycerols
Inhibits lipolysis in adipose tissue by inactivating hormone-sensitive lipase which mobilises fatty acids from triglyceride stores
Functions as a growth factor for some cells such as fibroblasts
Effects occur over several hours

Question 25

What are the 2 products of the pentose phosphate pathway?

Answer 25

Ribose phosphate

NADPH

Question 26

What is ribose phosphate used for?

Answer 26

Used to synthesis RNA & DNA

Question 27

What is NADPH used for?

Answer 27

Reductive biosynthesis & to maintain the redox balance of the cell

Question 28

What does tripeptide glutathione?

Answer 28

It maintains the redox balance of the cell. Maintained in the reduced state using NADPH.
This is particularly important in erythrocytes

Question 29

What is the pentose phosphate pathway?

Answer 29

Cytosolic pathway present in all cells

Branches from glycolysis at G-3-P

Question 30

Describe glucose metabolism in the heart & muscle

Answer 30

Insulin-sensitive Glut 4 transporter

Stored as glycogen or used to produce energy

Question 31

Describe glucose metabolism in the adipose tissue

Answer 31

Glut 4 transporter
Glycolysis produces acetyl CoA which can be used to produce ATP or synthesise fats
Some is used for the pentose phosphate pathway to produce NADPH

Question 32

Describe glucose metabolism in the RBC

Answer 32

Glut 1 transport system
Glycolysis to form lactate produces energy
Some is used in the pentose phosphate pathway to produce NADPH for the maintenance of reduced glutathione.
RBC don’t have mitochondria so can’t fully oxidise glucose via the TCA cycle & ETC. Rely on glycolysis for their energy requirement

Question 33

Describe glucose metabolism in the brain

Answer 33

Glut 1 & Glut 3 transport systems
Aerobic metabolism to produce energy
Some used in pentose phosphate pathway to provide NADPH for lipid synthesis

Question 34

Describe glucose metabolism in the liver

Answer 34

Glut 2 transport system
Stored as glycogen, glycolysis to form pyruvate & then acetyl CoA
Some produces ATP & excess acetyl CoA used for fat synthesis
Some glucose goes through pentose phosphate pathway to form NADPH to support fat biosynthesis.