Receptors and cell signalling

Question 1

Why do we need fuel stores?

Answer 1

Body cannot store ATP, it must be made in the cell at the time it is needed and at the rate it is needed by oxidising fuels hence why we need fuel stores
We need to maintain a supply of glucose between meals, provide immediate fuel for increased activity and have fuel for long periods when food intake may be inadequate

Question 2

Fuel reserves in normal subject

Answer 2

Average person carries around 15kg of fat, fuel reserve is around 15kg of adipose tissue, 590,000kJ stored for us to access, only need 10,000kJ a day
Glycogen storage for an average person is about 0.223kg
Circulating fat in transport for storage (fatty acids going around in the blood) is around 20g

Question 3

How is fat stored?

Answer 3

Triacylglycerols are stored as fat droplets in adipose tissue, excess fat from diet that we don’t use immediately for beta-oxidation can be converted and stored as fat, we have unlimited fat stores

Question 4

How are triacylglycerols synthesised?

Answer 4

In endoplasmic reticulum we form chylomicrons which is where fatty acids attach and are shunted into blood, move in circulation to adipose tissue
Glycerol backbone derived from glucose, activation of fatty acids to acyl-CoA oxidation of bond provides energy to form ester linkage (acyl groups to glycerol 3-phosphate), stimulated by insulin

Question 5

How is fat broken down?

Answer 5

Lipase breaks down fat, fat moves into cells, packaged into chylomicrons, move through circulation, stimulated by insulin
Chylomicrons arrive in capillaries of adipose tissue, lipase cleaves fatty acid off glycerol backbone, also activated by insulin, fatty acids deposited inside adipose tissue, remnants of chylomicrons go into liver and are degraded and recycled
Once in adipose tissue fatty acids are re-esterified and attached back onto glycerol backbone

Question 6

How is phosphorylation of downstream targets enabled?

Answer 6

Insulin binds to alpha domain causing conformational change of receptor, relayed through beta subunits, activates kinase, kinases ages phosphate from ATP and attaches it to amino acid group to enable phosphorylation of downstream targets (proteins in cytoplasm)

Question 7

How is fatty acid attached back onto glycerol?

Answer 7

CoA used to attach fatty acid back onto glycerol with a fatty acylCoA synthase and ATP which drives reaction to produce fatty acyl-CoA (attached by hydrolysing ester bond)

Question 8

How is glycerol formed from glycolysis ?

Answer 8

Formation of glycerol from glycolysis
DHAP can be converted to glycerol-P by glycerol-3-phosphate dehydrogenase
glycerol-P to glycerol to triacylglycerol requires several steps
glycerol-3-phosphate acyltransferase and phoshatidate phosphates followed by diacylglycerol acyltransferase

Question 9

How are triacylglycerols mobilised?

Answer 9

We need to hydrolyse TAG, hormone sensitive lipase drives reaction as a response to glucagon and adrenaline, releases free fatty acids and releases glycerol

Question 10

How is adrenaline or glucagon activated?

Answer 10

Activation of adrenaline or glucagon uses GPCR to signal molecule in cytosol to act upon protein kinase which phosphorylates lipase and produces a response bringing about a conformational change activating enzyme

Question 11

What is glycogen?

Answer 11

Glycogen is a branched polysaccharide that is stored in the liver and muscle which forms granules in cytoplasm
Glucose is stored in long chains connected through 1-4 alpha linkages and 1-6 glycosidic bonds

Question 12

What is glycogen synthesis?

Answer 12

Occurs mainly in liver and muscle immediately after meal
Requires high energy inputs, ATP and UTP, and activated high-energy precursors, UDP-glucose, and is stimulated by insulin

Question 13

How is glucose made into glucose 1-P

Answer 13

Glucose is made into glucose 6-P and enzyme called mutate moves phosphate group onto C1 rather than C6, once it becomes glucose 1-P enzymes of glycolysis can’t recognise it and it can be converted to glycogen

Question 14

How is glucose attached to glycogen chain?

Answer 14

Glucose 1-P is activated by creating a new ester bond donated by UTP (energy source), UTP attached to glucose and form UDP-glucose molecule, bond can be hydrolysed and attach glucose to growing chain of glycogen

Question 15

How is glycogen mobilised?

Answer 15

We can use glucose as a source of energy by degrading glycogen in glycogenolysis
Liver glycogen releases glucose into blood for the brain
Muscle glycogen is used to generate ATP for energy, releases fuel for glycolysis within muscle cells

Question 16

Can you get fat directly from glucose?

Answer 16

Excess glucose is converted into fatty acids, occurs mainly in liver, relatively complex process, requires energy, export TAGs out of liver as VLDL. Fatty acids stored as TAG’s in adipose tissue. Process stimulated by insulin

Question 17

What fuels are used for different tissues?

Answer 17

Brain uses glucose as cannot use fatty acids
Red blood cells use glucose
Liver and heart use mostly fatty acids
Muscle when resting uses mostly fatty acids, marathon uses a mix of fatty acids and glucose