The Liver In Metabolism: Glucose Homeostasis

Front 1

Why is glucose an important metabolic fuel?

Back 1

1. A source of energy

2. A source of NADPH needed for synthetic reactions (fatty acids, steroids)

3. A source of pentose sugars for synthetic reactions (nucleotides, DNA)

4. A source of carbon for other sugars and glycoconjugates

Front 2

What properties of glucose make it a good fuel?

Back 2

Water soluble so does NOT require a carrier in the circulation

Can cross the blood brain barrier

Can be oxidised anaerobically

Front 3

All tissues use glucose. What does the liver do in terms of glucose?

Back 3

The liver can provide glucose for other tissues

Front 4

What pathways is glucose involved in in skeletal muscle?

Back 4

Glycolysis

Glycogen synthesis and degradation

Front 5

What pathways is glucose involved in in the heart and brain?

Back 5

Glycolysis

Front 6

What pathways is glucose involved in in in adipose tissue?

Back 6

Glycolysis

Front 7

What pathways is glucose involved in in erythrocytes?

Back 7

Glycolysis

Pentose phosphate pathway

Front 8

What pathways is glucose involved in in the liver?

Back 8

Glycolysis

Pentose phosphate pathway shunt

Glycogen synthesis and degradation

Gluconeogenesis

Front 9

What is the function of glucose in the heart and brain?

Back 9

A source of energy

Front 10

What is the function of glucose in skeletal muscle?

Back 10

A source of energy

Anaerobic muscle contraction

(converted to glycogen) an energy store for muscle contraction

Front 11

What is the function of glucose in adipose tissue?

Back 11

Production of glycerol-3-phosphate for TAG's

Front 12

What is the function of glucose in erythrocytes? (red blood cells)

Back 12

A source of energy

(pentose phosphate pathway) produces NADPH for synthesis of fat, cholesterol and steroids

Front 13

What is the function of glucose in the liver?

Back 13

Produces acetyl CoA so excess glucose is converted into fatty acids

(pentose phosphate pathway) produces NADPH for synthesis of fat, cholesterol and steroids

store of glucose for other tissues

Front 14

What are the sources of glucose that are available to the body?

Back 14

Diet

Liver glycogen

Liver gluconeogenesis *

Front 15

In conditions of carbohydrate deprivation, glucose is synthesised from non-carbohydrate sources in the liver (gluconeogenesis). What are these sources?

Back 15

Lactate

Glycerol

Glucogenic amino acids

Other monosaccharides

Front 16

Can glucose be synthesised from fatty acids?

Back 16

NO!!!!!

Front 17

Which amino acids are glucogenic?

Back 17

All except leucine and lysine.

Front 18

After ingestion of 100g of glucose, what forms of glucose are used and in what order?

Back 18

Injested glucose

Glycogen

Gluconeogensis

Front 19

What kind of hormone is insulin and what does it promote?

Back 19

Anabolic hormone

promotes synthesis and storage

Front 20

What kind of hormone is glucagon and what does it promote?

Back 20

Catabolic hormone

promotes degradation of stored fuel

Front 21

Where are the Islets of Langerhans found?

What kind of cells make up the Islets of Langerhans?

Back 21

Pancreas

Beta cells (secrete insulin) and alpha cells (secrete glucagon)

Front 22

Insulin, glucagon (as well as adrenaline) and glucose, signal and coordinate the activities of which tissues?

Back 22

The liver

Adipose tissue

Muscle tissue

Front 23

What are some metabolic effects of insulin on the liver?

Back 23

Inhibition of gluconeogenesis

Activation of glycogen synthesis (glycogen synthase activated)

Increased fatty acid synthesis and lipid assembly

Increased amino acid uptake and protein synthesis

Front 24

What are the metabolic effects of insulin on muscle?

Back 24

Increased glucose uptake by increasing glucose transporters (GLUT 4)

Increased amino acid uptake and protein synthesis

Activation of glycogen synthesis ( glycogen synthase activated)

Front 25

What are the metabolic effects of glucagon?

Back 25

Increase in blood glucose by increasing glycogenolysis and gluconeogenesis (liver)

Increase in circulating fatty acids and ketone bodies

Decrease in plasma amino acids

Front 26

Why does glucagon cause a decrease in plasma amino acids?

Back 26

Increased uptake by the liver for gluconeogenesis

Front 27

Why does glucagon cause an increase in circulating fatty acids and ketone bodies?

Back 27

Increase in lipolysis in adipose tissue

Increase in fatty acid oxidation

Front 28

Why is gluconeogenis not simply the reversal of glycolysis?

Back 28

Because there are 3 irreversible reactions in glycolysis

Front 29

What are the 3 irreversible reactions in glycolysis?

Back 29

D-glucose ---> glucose-6-phosphate

Fructose-6-phosphate ---> fructose-1,6-bisphosphate

Phosphoenol pyruavte ---> pyruvate

Front 30

How is pyruvate converted to glucose?

Back 30

Pyruvate is first converted to oxaloacetate and then it is converted to phosphoenol pyruvate . The PEP is then converted to glucose via many stages.

Front 31

How is gluconeogenesis regulated?

Back 31

1. Mobilisation of substrate

(glycerol from fat breakdown, amino acids from muscle protein breakdown)

2. Activation of enzymes ( including pyruvate carboxylase)

Front 32

What activates pyruvate carboxylase?

Back 32

Acetyl CoA

Front 33

Which enzyme converts pyruvate to oxaloacetate?

Back 33

Pyruvate carboxylase

Front 34

Which enzymes converts oxaloacetate to PEP?

Back 34

PEP carboxykinase

Front 35

Following a meal, how are blood glucose and insulin levels related?

Back 35

They follow a similar pattern

Front 36

Following a meal, how are blood glucose and glucagon levels related?

Back 36

Glucagon pattern is opposite to glucose pattern

Front 37

What is the physiological circulating concentration of glucose?

Back 37

3.9-6.2 mM

Front 38

What are some disadvantages of glucose as a metabolic fuel?

Back 38

Relatively low yield of ATP/mole compared to fatty acids

Osmotically active

In high concentrations can directly damage cells or lead to accumulation of toxic by-products

Front 39

In the FED state, what is glucose converted to in the liver?

Back 39

Majority of glucose converted to glycogen

XS glucose converted to fat

Front 40

In the FED state, what is glucose converted to in the muscle?

Back 40

Glycogen

Front 41

In an aerobically respiring muscle, what is glucose converted to?

Back 41

Glucose AND glycogen are converted to pyruvate, which is then converted to acetyl CoA which ends the TCA cycle and then oxidative phosphorlyayion to produce ATP

Front 42

In erythrocytes, in the FED or fasting state, what is glucose converted to?

Back 42

Lactate

Front 43

When the liver is in the fasting state, what is converted to what?

Back 43

Lactate and glycogen are converted back to glucose

Front 44

When the brain is into the FED or fasting state, what is glucose converted to?

Back 44

Front 45

These are the glucose tolerance curves of normal and diabetic subjects. Which curve is for a normal person, one with type I diabetes and a person with type II diabetes?

Back 45

Front 46

What is the molecular basis for the observation that liver glycogen is used for maintaining blood glucose concentration but muscle glycogen is not?

Back 46

Muscle lacks the enzyme, glucose-6-phosphatase that catalyses the dephospho rylation of glucose-6-phosphate to glucose, whereas the liver has this enzyme.

In muscle glucose-6-phosphate is thus directed to glycolysis for ATP production within the muscle fibres, which makes sense as muscles require ATP for contraction

Front 47

What is the cofactor for pyruvate carboxylase?

Back 47

Biotin

Front 48

Where does carboxylation of pyruvate take place?

Back 48

Carboxylation of pyruvate occurs in themitochondria while other reactions of gluconeogenesis occur in the cytosol.

Front 49

One role of glucose in to provide NADPH in the hexose monophosphate shunt in which two places?

Back 49

Liver

Erythrocytes

Front 50

In which two places is the role of glycolysis not for energy?

Back 50

Adipose tissue ( to produce glycerol P' for TAGS)

Liver ( XS glucose converted to acetyl CoA)