Energy Storage

Question 1

Which tissues have an absolute requirement for glucose?

Answer 1

RBC
Neutrophils
Innermost cells of kidney medulla
Lens of eye

Question 2

What can hypoglycaemia lead to/cause? (ie symptoms)

Answer 2

Confusion
Weakness, nausea
Muscle cramps
Brain damage, death

Question 3

How is glycogen stored and where?

Answer 3

As granules; in the liver and muscle

Question 4

What is the structure of glycogen?

Answer 4

Highly branched polymer molecule with glucose subunit.

Chains originate from a dimer of the protein glycogenin at the centre.

Alpha-1,4 glycosidic bonds joining the chains.
Alpha-1,6 glycosidic bonds from branch points.

Question 5

What is glycogenin?

Answer 5

The protein at the centre of glycogen from which the chains branch from.

Question 6

Glycogenesis

Answer 6

Glycogen synthesis.
Glucose + ATP -> glucose-6-P + ADP
— hexokinase (glucokinase in liver)
Glucose-6-P -> glucose-1-P
— phosphoglucomutase
Glucose-1-P + UTP + H2O -> UDP-glucose +Pi
— G1P uridylyltransferase
Glycogen (n residues) + UDP-glucose -> glycogen (n+1 residues) + UDP
— glycogen synthase (extend chain - alpha-1,4)
— branching enzyme (form branch - alpha-1,6)

Question 7

Hexokinase
(What is this in the liver?)

Answer 7

Catalyses glucose to glucose-6-P.

Glucokinase in liver

Question 8

Phosphoglucomutase

Answer 8

Catalyses glucose-6-P to glucose-1-P as well as the reverse reaction.

Question 9

G1P uridylyltransferase

Answer 9

Catalyses glucose-1-P to UDP-glucose

Question 10

Glycogen synthase

Answer 10

Forms alpha-1,4 glycosidic bonds between glucose subunits to extend the chains in glycogen.

Question 11

Branching enzyme

Answer 11

Forms alpha-1,6 glycosidic bonds to form branches between glucose subunits in glycogen.

Question 12

Glycogenolysis

Answer 12

Breakdown of glycogen to produce glucose.

Question 13

Glycogen phosphorylase

Answer 13

Glycogen (n residues) + Pi -> glucose-1-P + glycogen (n-1 residues)

Breaks alpha-1,4 bonds

Question 14

De-branching enzyme

Answer 14

Breaks alpha-1,6 bonds

Question 15

Why is the use of different enzymes in glycogenolysis and glycogenesis important?

Answer 15

Using different enzymes allows for the simultaneous inhibition of one pathway and the stimulation of the other.

Question 16

How is glycogenolysis different in skeletal muscle to the liver?

Answer 16

Skeletal muscle lacks glucose-6-phosphatase, so doesn’t produce glucose and instead stops at glucose-6-P, which feeds into glycolysis.

Question 17

What is the rate limiting enzyme for glycogen synthesis?

Answer 17

Glycogen synthase

Question 18

What is the rate limiting enzyme of glycogen degradation?

Answer 18

Glycogen phosphorylase

Question 19

Glycogen storage diseases
(No specific diseases)

Answer 19

Inborn errors of metabolism - inherited diseases.
Arise from deficiency or dysfunction of enzymes of glycogen metabolism.

Question 20

Gluconeogenesis - what is it?
Where does it occur?

Answer 20

Synthesising glucose from alternative source (not glycogen).
Occurs in liver and to a lesser extent in kidney cortex.

Question 21

What are the three major precursors of gluconeogenesis?

Answer 21

Lactate (from anaerobic glycolysis)

Glycerol (from breakdown of fats)

Amino acids (mainly alanine)

Question 22

What are the three key enzymes in gluconeogenesis?

Answer 22

Glucose-6-phosphatase

Fructose 1,6-bisphosphatase

Phosphoenolpyruvate carboxykinase (PEPCK)

Question 23

What hormones stimulate gluconeogenesis?

Answer 23

Glucagon, cortisol

Question 24

What hormone inhibits gluconeogenesis?

Answer 24

Insulin

Question 25

What is the time course of glucose utilisation?

Answer 25

(Feeding occurs at hour 0)

Glucose from food - about 2 hours

Glycogenolysis - up to 8-10 hours

Gluconeogenesis - 8-10 hours onwards

Question 26

What form are lipids stored in?

Answer 26

Anhydrous

Question 27

Define adipocytes

Answer 27

Cells containing large lipid droplet (mainly TAG and cholesterol ester).

Cytoplasm and organelles pushed to edge.

Cells expand as more fat is added.

Question 28

How do FA travel in the blood?

Answer 28

Binds to albumin

Question 29

What enzyme catalyses TAGs to fatty acids and glycerol?

Answer 29

Pancreatic lipase

Question 30

Lipogenesis

Where does it occur?

Answer 30

Fatty acid synthesis.
Occurs mainly in liver.
Converts glucose to pyruvate.

Pyruvate then enters mito and forms acetyl-CoA and OAA -> condense to form citrate.

Citrate re enters cytoplasm and cleaved back to acetyl-CoA and OAA.

Question 31

What enzyme regulates lipogenesis?

Answer 31

Acetyl-CoA carboxylase

Question 32

Fatty acid synthase complex

Answer 32

Builds FA by sequential addition of addition of 2C units provided by malonyl-CoA

Question 33

What hormone/other molecules increase activity of lipogenesis in the liver?

Answer 33

Insulin and citrate (not a hormone lmao)

Question 34

What hormones/other molecules decrease activity of lipogenesis in liver?

Answer 34

Glucagon and adrenaline, and AMP

Question 35

Comparison of fatty acid synthesis and beta-oxidation

Answer 35

Fatty acid: occurs in mito, oxidative (produces NADH and FAD2H), is inhibited by insulin

Beta-oxidation: occurs in cyto, reductive (requires NADPH), is stimulated by insulin

Question 36

Lipolysis

Answer 36

Fat mobilisation

Hormone sensitive lipase:
- glucagon and adrenaline activate this
- insulin inhibits this

HSL breaks down TAG to form glycerol and free FA in blood.

=> insulin decreases lipolysis and vice versa.