Module 1.4 - Metabolism

Question 1

What is the structure of glycogen

Answer 1

Glycogen is a polysaccharide comprised of alpha-D-glucose units linked via a1-4 glycosidic bonds with a1-6 branch points

Question 2

What is glycogen and what does it do?

Answer 2

Glycogen is the storage form of carbohydrate in the body. It is critical during fasting, since liver glycogen provides a source of blood glucose. Muscle glycogen cannot give rise to blood glucose, but is used to power muscle contraction for extended periods of time.

Question 3

Glycogenolysis

Answer 3

The breakdown of glycogen and involves the enzymes glycogen phosphorylase, debranching enzyme and phosphoglucomutase

Question 4

Glycogenesis

Answer 4

the synthesis of glycogen and involves the enzymes UDP-glucose pyrophosphorylase, glycogen synthase, amylo (1-4) to (1-6) transglycosylase (glycogen-branching enzyme)

Question 5

The Cori Cycle

Answer 5

also known as the lactic acid cycle, is a metabolic pathway where lactate produced by anaerobic glycolysis in muscles is transported to the liver, converted to glucose, and then returned to the muscles to be metabolized again

Question 6

Glucagon signalling

Answer 6

initiated by glucagon binding to its receptor, primarily increases blood glucose levels by promoting glycogenolysis and gluconeogenesis through the activation of the cAMP-PKA pathway, ultimately leading to the release of glucose from the liver. - Glucagon is the primary messenger
- cAMP is made from ATP by the enzyme Adenylate Cyclase (AC)
- cAMP activates PKA allosterically and when activated PKA phosphorylates several protein targets on Ser/Thr residues
Liver PFK-2 is inactivated and FBP-ase-2 activated when a Ser residue in the regulatory domain is phosphorylated by PKA
PEPCK

Question 7

Adrenaline signalling

Answer 7

cAMP-dependent kinase and everything downstream are also switched on by adrenaline binding to the beta-adrenergic receptor but hepatocytes are more responsive to glucagon. In liver - Adrenaline switches on gluconeogenesis and glycogenolysis. In muscle - adrenaline switches on glycolysis and glycogenolysis

Question 8

Tissue specialisation - brain

Answer 8

fuel sources - glucose is major fuel for the human brain
- brain can adapt to ketone bodies during starvation (>3 days) and danger occurs when [glucose]< 2.2 mM
- fuel stores: brain lacks fuel stores therefore relies on a constant supply of blood glucose via GLUT3 Km 1.0 mM
- resting conditions: brain consumes 60% of total GNG glucose in the resting state

Question 9

Tissue specialisation - muscle

Answer 9

fuel sources: glucose, fatty acids and ketone bodies
fuel stores: muscle stores 75% of total body glycogen and can represent 1% of muscle weight after a meal (provides glucose locally - doesn’t contribute to blood glucose)
resting conditions: muscle utilises fatty acids as the major fuel in the resting state (85% of energy). heart muscle uses one of the ketone bodies, acetoacetate, in preference to glucose
Muscle and liver metabolites connected by the Cori cycle

Question 10

tissue specialisation - adipose (fat)

Answer 10

fuel sources: requires glucose to perform major task of synthesising and storing triacylglycerol, which is mobilised during fasting
fuel stores: in a 70kg person, adipose stores >80% of total available energy
resting conditions: highly active during starvation (decreased insulin activates hormone-sensitive lipase which breaks down TAG)