L12: glucose/lipid/protein metabolism

Question 1

What is metabolism?

Answer 1

Energy provision, storage and use

Question 2

Where does energy come from?

Answer 2

Diet - carbs, lipids, proteins (a.a.s)

Question 3

How is energy stored in our body?

Answer 3

Carbs stored as glycogen

Fats stored as triglycerides

Question 4

What is energy most stored as?

Answer 4

Fats because fats are more energy dense

Question 5

Why are carb stores needed?

Answer 5

Main source of energy in the short term

Question 6

What organs are involved in fuel metabolism?

Answer 6

Pancreas is a regulator (it secretes hormones)

Liver, muscle and adipose tissue are all effectors

Question 7

What is glycogen?

Answer 7

• storage polymer of glucose
• contained in liver and muscle - mainly muscle due to high energy demand
• provides 40-80% plasma glucose during 24hr fast
• insoluble molecule so does not affect osmosis of cells unlike glucose

Question 8

Structure of glycogen

Answer 8

Highly branched polymer of glucose with both alpha1,4 and alpha1,6 glycosidic linkages
1,6 bonds cause branching
Many branches (around 1 every 10residues) allows more rapid release of glucose by faster breakdown of glycogen (greater SA)
(Image at 7:30)

Question 9

How is glycogen made?

Answer 9

Made in glycogen granules
Enzyme - glycogenin allows the first few glucose molecules (at least 3) to link together in the process of forming glycogen (priming molecule)
Once 3 glucose molecules are linked by glycogenin, another enzyme called glycogen synthase adds extra glucose molecules

Question 10

Glucose into glycogen (explanation)

Answer 10

1. Glucose is converted into glucose-6-phosphate by the addition of a phosphate. Catalysed by glucokinase in the liver or hexokinase in the muscle.
2. Phosphate on C6 moves to C1 by phosphoglucomutase to form glucose-1-phosphate
3. Glucose-1-phosphate can be converted to glucose via glycogen synthase

Question 11

Glucose pathways flow chart

Answer 11

Minute 10

Question 12

Glycogen into glucose (explanation)

Answer 12

A glycogen molecule with n number of glucose molecules will release one glucose-1-phosphate molecule, leaving us with a glycogen molecule with one less glucose, n-1.
Regulated by glycogen phosphorylase

Question 13

How is glycogen synthase regulated by hormones?

Answer 13

Positive activation by high levels of glucose due to high glucose causing high insulin levels. So insulin promotes glucose into glycogen.
Adrenaline and muscle contraction inhibit glycogen synthase, preventing G1P into glycogen.

Question 14

How is glycogen phosphorylase regulated by hormones?

Answer 14

Adrenaline, glucagon and muscle contraction stimulate glycogen to glucose.

Question 15

How do the uses of glucose differ in the liver and in the muscle?

Answer 15

Muscle has a high storage concentration of glycogen verse the liver
The liver is an organ which when it generates glucose, it releases it into circulation, to supply us with glucose in between food/during fasting
Muscle will use the energy generated from glucose metabolism for contraction

Question 16

Difference between the release of glucose in muscle and liver

Answer 16

Glycogen will release a glucose molecule under the activity of glycogen phosphorylase to form G1P.
G1P is metabolised to G6P by phosphoglucomutase
G6P is trapped within the cell. Can be used to generate energy by entering the glycolysis cycle (predominant in the muscle)
If G6P is metabolised by removing the phosphate to generate glucose via glucose 6 phosphatase, then glucose can move out of a tissue if there are transporter molecules on its surface of the cell (predominant in liver)

Question 17

Effects of muscle contraction on glucose levels

Answer 17

Muscle contraction enables the generation of glucose:

• when a muscle contracts calcium ions are released from SR
• the increase in cytoplasmic calcium ions causes a conformational change in Phosphorylase B kinase which adds a phosphate group to phosphorylase B (inactive) to form phosphorylase A phosphatase (active)
• phosphorylase A enables the activity of glycogen breakdown into G1P by enabling glycogen phosphorylase to be active
• allows glycolysis causing ATP and thus muscle contraction

Question 18

Effects of adrenaline on glucose levels

Answer 18

(Flow diagram at 23:10)
Key points
- adrenaline has the combined effects of inhibiting glycogen synthesis and increasing glycogen breakdown to release glucose for the fight or flight response
- adrenaline actives protein kinase A
- protein kinase A phosphorylase phosphorylase kinase to activate it, which activates glycogen phosphorylase b into a

• at the same time adrenaline also inhibits glycogen synthase: protein kinase A inactivates glycogen synthase a into b by phosphorylating it

Question 19

Why does adrenaline need the dual role?

Answer 19

Important to prevent the continual recycling of glucose
If adrenaline did not have this role of inhibition of glycogen synthase, then the glucose produced for the fight or flight response would just be converted back into glycogen

Question 20

What are lipids?

Answer 20

• a dense source of energy
• insoluble in water
• fatty acids can have detergent-like properties

Question 21

Main store of fats

Answer 21

Lipid = fatty acid and glycerol
Fatty acids are slightly soluble in water - bind to plasma proteins, depends on pH,
Fatty acids are often stored as Triacylglycerol (TAG) = 3 fatty acids linked to a glycerol
These are completely insoluble in water
Lipoproteins will make them more soluble

Question 22

Where are lipoproteins synthesised

Answer 22

• intestine - areas where fats are absorbed. Produces a chylomicron (CM)
• liver - will produce a VLDL (very low density lipoprotein)

Question 23

Different lipoproteins

Answer 23

Chylomicron (CM) is produced within intestine to transport our dietary uptake of fat into the body.
VLDL is a primary lipoprotein that leaves the liver.
Main difference between VLDL and other lipoproteins like IDL,LDLHDL, is the concentration of fat and cholesterol within them. VLDL will have higher conc of triglycerides, which drops down through the IDL,LDL,HDL, leaving more cholesteryl esters
CM has a major lipid of TG
On the surface of these vesicles are lipoproteins which are apoB (mainly)

Summary table at min 5

Question 24

Major facts about chylomicron

Answer 24

• synthesised in the gut
• derived from dietary fatty acids
• fatty acid predominantly as core triacylglycerol
• comprise apolipoprotein B48 scaffolding surrounding lipid
• episodic, post-prandial flux

Question 25

Major facts about very-low density lipoproteins

Answer 25

• synthesised by the liver
• fatty acid derived from adipose tissue and de novo lipogenesis
• fatty acid predominantly as core triacylglycerol
  Comprise apolipoprotein B100 skeleton surrounding lipid with (apo C and apo E)
• increased production on fasting

Question 26

Objective for CM and VLDL

Answer 26

Objective is for CM to take the TAGs and circulate them to enable tissues to store the fat that comes from them. It will be metabolised and leave behind a chylomicron remnant.
Objective for VLDL is to come from the liver to do the same job. Take the TAGs to tissues for storage.

Question 27

What is apolipoprotein B

Answer 27

Found in two forms in humans
ApoB100 synthesised in the liver
ApoB48 synthesised in enterocytes
Both are insoluble proteins (when not combined with fats)
Contain strongly hydrophobic regions
Both derived from the same mRNA

Question 28

Where are apoB100 and apoB48 truncated?

Answer 28

• apoB100 in the liver remains as a full length protein
• in the intestine before the protein is made, only 48% of that gene is utilised to produce the protein

Editing of mRNA occurs at a post-transcriptional level before RNA is converted to protein