BMS07-1032/33 Integration of Metabolism

Question 1

Fed state

Answer 1

Fuel comes from food your eating

Question 2

Fasting state

Answer 2

Fuel comes from stores put down during the fed state

Question 3

What controls how much fuel we store?

Answer 3

Hormones

Question 4

How does starvation alter metabolism

Answer 4

Cells start metabolising different fuels

Question 5

How do enzymes alter metabolism (3)?

Answer 5

Allosteric regulation
Covalent modification
Changing their synthesis

Question 6

ADP + ADP =

Answer 6

ATP & AMP

Question 7

How does AMP affect phosphofructokinase?

Answer 7

Activates it

Question 8

What molecule does phosphofructokinase act on?

Answer 8

Phosphorylates fructose-6-phosphate

Question 9

What will/wont the liver respond to?

Answer 9

Responds to hormones not low levels of ATP

Question 10

What activates glycogen phosphorylase?

Answer 10

Glucagon by adding a Pi to it

Question 11

Which 2 molecules is this enzyme related to?

Answer 11

Glycogen to glucose-1-phosphate

Question 12

What happens when there is low cholesterol?

Answer 12

HMG coenzyme A reductase is made to make cholesterol if enough isn’t being taken in through the diet

Question 13

The liver only takes up glucose when there is lots of it to ensure…

Answer 13

Ensures glucokinase is only made when theres lots of glucose for it to phosphorylate

Question 14

Which hormones alter the effects of insulin? (3)

Answer 14

Adrenaline
Cortisol
Growth hormone

Question 15

Which hormone do alpa cells release?

Answer 15

Glucagon

Question 16

When do beta cells release insulin?

Answer 16

When glucose enters them, they have a low affinity for this so it only occurs in high concentrations

Question 17

What type of cells are they?

Answer 17

Endocrine

Question 18

What % are alpha cells?

Answer 18

30-40%

Question 19

What do omega cells release?

Answer 19

Somatostatin

Question 20

What is somatostatin?

Answer 20

Growth hormone inhibitor

Question 21

What stimulates insulin secretion?

Answer 21

Glucose
AA
Hormones released after eating before glucose levels rise
Glucagon

Question 22

What is the role of glucagon?

Answer 22

Fine tuning of glucose levels

Question 23

Which hormones are released after eating?

Answer 23

Gastrointestinal hormones and secretin

Question 24

Describe insulin secretion?

Answer 24

AA or glucose enter the beta cell
ATP is made
ATP closes K channels
Membrane gets depolarised
Ca channels open
Insulin vesicles move

Question 25

Compare the effects of AA and glucose on beta cells

Answer 25

AA don't lead to as much insulin being released

Question 26

Proinsulin is converted to...

Answer 26

Insulin and C-peptide

Question 27

Metabolic effects of insulin

Answer 27

``` Fuel storage Growth Glycogen synthesis/storage AA uptake and protein synthesis FA storage ```

Question 28

How are fatty acids stored?

Answer 28

Acetyl coenzyme A is converted to malonyl coenzyme A which is involved in protein synthesis

Question 29

What makes up the bottom half of the insulin receptor?

Answer 29

Tyrosine kinase | Insulin receptor substrate docking site

Question 30

What happens at her IRS docking site?

Answer 30

It gets phosphorylated which activates a kinase which continues to activate other kinase by phosphorylation until the active protein kinase is reached

Question 31

What does active protein kinase do? (2)

Answer 31

Kinase moves the GLUT4 receptor to the membrane Phosphorylate glucose synthase kinase making it inactive so glycogen synthase doesn't get phosphorylated so its active and can form glycogen

Question 32

How does insulin affect lipolysis?

Answer 32

Inhibits protein kinase A by removing the cAMP activator using phosphodiesterase which active protein kinase activated This means hormone sensitive lipase isn't activated by protein kinase A so FA aren't stored

Question 33

How does insulin affect gene expression?

Answer 33

The receptor is phosphorylated due to the presence of insulin This activated RAS which activates kinases and then MAPK which influences transcription factors

Question 34

When is RAS active and inactive?

Answer 34

Active has GTP bound | Inactive has GDP

Question 35

Whats special about the GLUT4 receptor in the brain, liver, RBC and pancreas?

Answer 35

They aren't insulin dependant so glucose can be uptaken even when in low concentration

Question 36

What stimulates the release of glucagon?

Answer 36

Low blood glucose High AA Adrenaline

Question 37

What happens when there are high AA?

Answer 37

Releases both insulin and glucagon

Question 38

What does adrenaline do?

Answer 38

Supress insulin secretion Mobilises fuel in stress Glucose secretion FA release

Question 39

What does glucagon do?

Answer 39

``` Mobilise fuel Maintains glucose in fasting Glycogenolysis Gluconeogensis AA uptake at the livere FA release FA oxidation Ketone body formation in the liver ```

Question 40

How do GI hormones get to the liver?

Answer 40

In the pancreatic vein

Question 41

How does glucose get to peripheral tissue?

Answer 41

Travel down the hepatic vein

Question 42

What do GI hormones do?

Answer 42

Stimulate Islets of Langerhans

Question 43

What does cortisol do?

Answer 43

Glyconeogensis FA release AA mobilisation from the muscle

Question 44

What does insulin inhibit and what are the consiquences of this?

Answer 44

Protein kinase so glycogen isn't made

Question 45

When isn't the liver in glycogensis?

Answer 45

Fasting state

Question 46

Why does the liver have a low affinity for glucose?

Answer 46

So it doesn't compete with the brain

Question 47

What is gluconeogenesis?

Answer 47

Breaking down of non sugars for energy e.g. lactate, glycerol and AA

Question 48

Glycogensis

Answer 48

Breaking down glycogen

Question 49

Glycolysis

Answer 49

Making glycogen

Question 50

What activates glycolysis?

Answer 50

Glucokinase/pyruvate kinase/ phosphofructokinase

Question 51

What happens to glycogen in the fasting state?

Answer 51

It is broken down

Question 52

What happens to glycogen synthase in the fasting state?

Answer 52

Inhibited, phosphorylase is inhibited so it cant turn the enzyme on

Question 53

How are fatty acids prevented from being esterified?

Answer 53

Malonyl coenzyme A inhibits carnitine transferase so FA cat enter the mitochondria to be oxidised

Question 54

What is activated to prevent FA synthesis?

Answer 54

Acetyl coenzyme A carboxylase

Question 55

What has a greater uptake in the fasting state in muscles?

Answer 55

AA, so protein synthesis

Question 56

What activates lipoprotein lipase and what does this cause?

Answer 56

Insulin so FA can enter adipose tissue for esterification

Question 57

The inhibition of which enzyme results in FA being broken down?

Answer 57

Hormone sensitive lipase

Question 58

After how long will all glycogen stores have been used up?

Answer 58

24hrs

Question 59

What inhibits pyruvate dehydrogenase to stop pyruvate being converted to...

Answer 59

Glucagon inhibits and insulin activates so its not converted to acetyl coenzyme A and its used to make glucose

Question 60

What happens to an excess of acetyl coenzyme A?

Answer 60

Put into FA synthesis when acetyl A carboxylase is activated, this means glucose formation is favoured

Question 61

What metabolism is useful for long term starvation?

Answer 61

Ketone

Question 62

Where are ketone bodies sent and why?

Answer 62

Into circulation as the liver cant use them

Question 63

What makes ketone bodies?

Answer 63

Acetyl coenzyme A

Question 64

Which tissues oxidise FA and ketone bodies?

Answer 64

Most

Question 65

How can the brain use ketone bodies?

Answer 65

They are small and lipid soluble so they can cross the barrier

Question 66

What do ketone bodies do?

Answer 66

Get beta cells to make insulin and inhibit the breakdown of AA

Question 67

Give 2 examples of ketone bodies

Answer 67

Acetoacetate and beta hydroxybutyrate

Question 68

What do muscles use in extreme starvation?

Answer 68

Fatty acids

Question 69

What happens to the concentration of ketone bodies and fatty acids?

Answer 69

FA plateu but ketone bodies continue to increase

Question 70

Complications of type 2 diabetes

Answer 70

Blindness Foot ulcers Thickened basement membrane Kidney failure

Question 71

Treating type 2 diabetes

Answer 71

Biguanides (increase GLUT4 receptors), sulphonylureas (insulin secretion) and oral hypoglycaemic

Question 72

What happens in type 1 diabetes?

Answer 72

Insulin cant prevent the breakdown of protein and fat Similar to starvation Ketone bodies are made