L3: Glycogen & Fat

Question 1

Some tissues will only metabolise glucose; state some examples

Answer 1

RBC, neutrophils, lens of eye, innermost cells of kidney medulla

Question 2

State the two main places glycogen is stored and in what quantities

Answer 2

• Muscles (300g) - Liver (100g)

Question 3

Describe the structure of glycogen

Answer 3

Carbohydrate polymer consisting of chains of glucose residues. Chains are organised as branches originated from a dimer of glycogenin (protein) at the core of the structure. Glucoses residues linked by alpha 1,4- and 1,6- glycosidic bonds forming branch points every 8-10 residues

Question 4

Which type of glycosidic bonds join chains in glycogen?

Answer 4

alpha 1,4-glycosidic bonds

Question 5

Which type of glycosidic bonds form branch points in glycogen?

Answer 5

alpha 1,6-glycosidic bonds

Question 6

Stable blood glucose is essential for…

Answer 6

Normal brain function!

Question 7

State two advantages of glycogen having a highly branched structure?

Answer 7

• Many sites for glucose addition or removal so rapid degradation (to release energy) or synthesis possible - Many glucose residues can be stored with minimal osmotic effect due to the large size of glycogen (NOTE: there is a limit to how much can be stored without having an osmotic effect as glycogen is polar)

Question 8

Define glycogenesis

Answer 8

Synthesis of glycogen from glucose

Question 9

Describe the 4 steps of glycogenesis

Answer 9

Question 10

What is UDP-glucose?

Answer 10

Highly activated form of glucose

Question 11

Define glycogenolysis

Answer 11

Breakdown of glycogen into glucose-6-phosphate (liver & muscle) and glucose (LIVER ONLY)

Question 12

Desribe 2/3 steps of glycogenolysis

Answer 12

Question 13

Is glycogenolysis a simple reversal of glycogenesis?

Answer 13

No. Different enzymes for each. This allows simultaneous inhibition of one pathway and stimulation of the other

Question 14

State the key regulatory enzyme in glycogensis and how it is activated

Answer 14

• Glycogen synthase
• Activated by de-phosphorylation

Question 15

State the key regulatory enzyme in glycogenolysis and how it is activated

Answer 15

• Glycogen phosphorylase
• Activated by phosphorylation

Question 16

Describe the effects of the following three hormones on the two regulatory enzymes in glycogenesis & glycogenolysis:

• Glucagon
• Insulin
• Adrenaline

Answer 16

• Glucagon - starved state - degrade glycogen - stimulate glycogen phosphorylase
• Insulin- fed state - synthesise glycogen - stimulate glycogen synthase
• Adrenaline - fight or flight so need energy - degrade glycgoen - stimulate glycogen phosphorylase

Question 17

Glucagon, insulin & adrenaline have effects on glycogen synthase and glycogen phosphorylase; however, there are 2 exceptions to the ‘generic rules/efffects’ of these hormones

Answer 17

• Glucagon has no effect on muscle glycogen stores as there are no glucagon receptors
• AMP= allosteric activator of muscle glycogen phosphorylase (NOT IN LIVER)

Question 18

Describe the cycle of glycogen metabolism starting from glucose abosorption to glycogen breakdwon and glucose release in starved state. Include:

• Intermediates
• Enzymes
• Is reaction reversible?
• Is energy used

Answer 18

Question 19

Why does muscle not convert G-6-P into glucose?

Answer 19

Lacks enzyme glucose-t-phosphatase

Question 20

Describe what is meant by a glycogen storage disease and state 3 possible consequences of glycgoen storage diseases

Answer 20

Deficiency or dysfunciton of enzymes in glycogen metabolism. Severity, and symptoms, depend on which enzyme or tissue is affected.

Possible consequences:

• Excess glycogen storage leading to tissue damage
• Diminished glycogen stores leading to hypoglycaemia & poor exercise tolerance
• Abnormal glycogen structure

Question 21

Give 2 examples of glycogen storage diseases and describe the abnormality in each

Answer 21

• Von Gierke’s disease: glucose-6-phosphatase deficiency so can’t convert glucose-6-phosphate to glucose to be released; causes hepatomegaly
• McArdle disease: muscle glycogen phospharylase deficiency so can’t degrade glycogen leading to insufficient energy for muscle contraction

Question 22

Define gluconeogenesis

Answer 22

Synthesis of glucose from non-carbohydrate substances

Question 23

State the 3 precursors for gluconeogenesis

Answer 23

• Lactate
• Glycerol (from adipose tissue)
• Amino acids (whose metabolims involves pyruvate or intermediates of TCA cycle)

Question 24

Explain why, and when, gluconeogenesis is needed

Answer 24

Eating provides enough food for ~2 hours. Glycogenolysis can provide enough food for up to 8 hours. Beyond 8 hours, fasting liver glycogen stores start to be depeleted hence need another source of glucose. Gluconeogensis then occurs in liver and kidney cortex

Question 25

Where does gluconeogenesis occur?

Answer 25

Liver (mainly) & kidney cortex (less)

Question 26

State the three key regulatory enzymes in gluconeogenesis and state which two are majorly controlled

Answer 26

* **PEPCK (phosphoenolpyruvate carboxykinase)** * **Fructose 1,6-bisphosphatase** * Glucose-6-phosphatase \*\*\*Ones in bold are majorly controlled

Question 27

PEPCK is a key regulatory enzyme in gluconoegenesis; state it's reactants and products

Answer 27

Oxaloacetate --\> phosphoenolpyruvate

Question 28

Fructose 1,6-bisphophatase is a key regulatory enzyme in gluconeogenesis; state it's reactants and products

Answer 28

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

Question 29

Glucose-6-phophatase is a key regulatory enzyme in gluconeogenesis; state it's reactants & products

Answer 29

Glucose-6-phosphate --\> glucose

Question 30

State the effects of glucagon & cortisol on: * PEPCK * Fructose-1,6,-bisphosphatase (two key regulatory enzymes in gluconeogensis)

Answer 30

* PEPCK: increase amount * Fructose-1,6-bisphosphatase: increase amount & activity (ACTIONS STIMULATE GLUCONEOGENESIS)

Question 31

State the effect of insulin on: * PECK * Fructose-1,6-bisphophatase (TWO KEY REGULATROY ENZYMES IN GLUCONEOGENESIS)

Answer 31

* PEPCK: decreased amount * Fructose-1,6-bisphophatase: decreased amount and activity (BOTH ACT TO INHIBIT GLYCOLYSIS)

Question 32

Why is there no net synthesis of glucose from acetyl-CoA?

Answer 32

It can't be converted back to pyruvate (irreversible)

Question 33

Why does fatty acid oxidation release more energy than carbohydrate breakdown?

Answer 33

TCAs more reduced than carbohydrates

Question 34

When are TACs used? Their storage and mobilisation is under what control?

Answer 34

Prolonged stress, exercise, starvation and pregnancy. Storage and mobilisation under hormonal control.

Question 35

Why is it easy to put weigth back on once you have lost it?

Answer 35

Adipocytes can increase by four fold before dividing and increasing in number. Adipocytes can hold more fat.

Question 36

Weight gain is due to...?

Answer 36

Increased TCAs

Question 37

Desribe TCA metabolism starting from fat in small intestine to energy

Answer 37

Question 38

Why does fatty acid oxidation not occur in: * Brain * RBCs

Answer 38

* Brain: fatty acids don't cross blood brain barrier easily * RBCs don't have mitochondria

Question 39

Describe four main steps in lipogenesis (fatty acid synthesis) in liver

Answer 39

1. Glucose -\> pyruvate in cytoplasm (GLYCOLYSIS) 2. Pyruvate enters mitochondria and forms acetyl-CoA and Oxaloacetate 3. Acetyl carboxylase enzyme produces malonyl-CoA from acetyl CoA in cytoplasm 4. Fatty acid synthase complex builds fatty acids by adding 2C (from malonyl-CoA) each time

Question 40

What two energy molecules does lipogenesis in liver require?

Answer 40

* ATP * NADPH

Question 41

During lipolysis, what enzyme breaks down TCAs into gycerol and free fatty acids which are then released into blood?

Answer 41

Hormone sensitive lipase

Question 42

Describe the effects of: * Glucagon & adrenaline * Insulin ... on hormone sensitive lipase in fat mobilisation/lipolysis. State whether each phosphorylate or dephosphorylates HSL

Answer 42

* Glucagon & adrenaline: activate HSL by phosphorylation * Insulin: inhibits HSL by de-phosphorylation

Question 43

State the path/fate of the two following products (which are breakdown products of TCAs): * Glycerol * Free fatty acids

Answer 43

* Glycerol: travels to liver and utilised as carbon source for gluconeogenesis * Free fatty acids: travels complexed with albumin to muscle & other tissues

Question 44

Compare fatty acid oxidation and fatty acid synthesis, consider: * Add or remove C * Produce or use acetyl Co-A * Where * Oxidative or reductive * ATP required * Actions of insulin * Actions of glucagon & adrenaline

Answer 44

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