Integration of metabolism

Question 1

what are the metabolic features of skeletal muscles?

Answer 1

1) oxidative phosphorylation to make ATP for light contraction
2) when ATP consumption > ATP synthesis glycogen broken down
3) anaerobic conditions: pyruvate → lactate
4) relies on carbohydrate (glucose) + fatty acid oxidation

Question 2

what are the metabolic features of the brain?

Answer 2

1) can not metabolise fatty acids (slow across blood-brain barrier)
2) ketone bodies can partially be used instead of glucose
3) susceptible to hypoglycaemia - faintness + coma
4) susceptible to hyperglycaemia - irreversible damage
5) uses 20% of resting metabolic rate (ie. high ATP requirement)

Question 3

what are the metabolic features of the heart?

Answer 3

1) rich in mitochondria + completely aerobic mechanism

2) can oxidise fatty acids + carbs, ketone bodies

Question 4

what are the metabolic features of the liver?

Answer 4

1) wide repertoire of metabolic processes
2) high metabolic rate (20%)
3) can interconvert nutrient types
4) role in blood glucose levels at 4-5.5 mM
5) storage organ for glucose
6) role in lipoprotein metabolism

Question 5

what are the metabolic features of adipose tissues?

Answer 5

long term energy store for fatty acids in the form of triglycerides

Question 6

what can excess glucose-6-phosphate be used for if not in glycolysis?

Answer 6

to generate glycogen

Question 7

what can excess Acetyl CoA be used for if not in the TCA cycle?

Answer 7

fatty acids (stored as triglycerides in adipose tissues), cholesterol

Question 8

what happens to the Acetyl CoA in periods of fasting?

Answer 8

rather than enter the TCA cycle much of it is used in ketone body production

Question 9

what happens to pyruvate in periods of extreme exercise when the muscles can’t respire anaerobically?

Answer 9

lactate is produced in anaerobic respiration

Question 10

what can the intermediates of the tca cycle generate?

Answer 10

some amino acids

Question 11

what can pyruvate be a source of?

Answer 11

some amino acids (therefore some nucleotides)

Question 12

what happens to Glucose-6-phosphate via the pentose phosphate pathway?

Answer 12

It can be used as a source of nucleotide production

i.e. g-6-p → pentose phosphate → nucleotides

Question 13

how does the body avoid hypoglycaemia in the short term?

Answer 13

(not enough glucose)

1) Liver glycogen → glucose
2) Release of fatty acids from adipose tissues stored as triglycerides
3) aCoA → ketone bodies via liver

ketone bodies + fatty acids can be used by muscle as a glucose substitute

Question 14

how does the body avoid hypoglycaemia in the long term?

Answer 14

gluconeogenesis (as otherwise all glucose will be exhausted by 12-18 hrs)

Question 15

what are the steps involved in gluconeogenesis?

Answer 15

(essentially the reverse of glycolysis but don’t say that as there has to be a bypass reaction as some glycolysis reactions are irreversible (a straight reversible would be +90kJ deltaG so unfavourable)

pyruvate → oxaloacetate → phosphoenol pyruvate → G3P → fructose1-6-bP → f-6-p → glucose-6-phosphate → glucose

Question 16

how can lactate be used to generate pyruvate?

Answer 16

when rate of glycolysis > rate of TCA cycle + ETC

lactate –(lactate dehydrogenase)→ pyruvate

Question 17

how can some G3P be generated?

Answer 17

triglycerides → glycerol (+ fatty acids) → DHAP → G3P

Question 18

how is pyruvate converted to phosphoenolpyruvate in gluconeogensis?

Answer 18

1) pyruvate –(pyruvate carboxylase)→ oxaloacetate –mitochondria
2) oxaloacetate –(p..vate carboxykinase)→ phosphoenolpyruvate

Question 19

how is fructose-1,6-bisP converted to fructose-6-p in gluconeogenesis?

Answer 19

fructose-1,6-bisphosphatase

Question 20

how is glucose-6-P converted to glucose in glyconeogenesis?

Answer 20

glucose-6-phosphatase

Question 21

which types of amino acids can be used in gluconeogenesis?

Answer 21

glucogenic a-a —- their skeletons can give rise to glucose via gluconeogenesis

Question 22

which types of amino acids can be used to synthesise ketone bodies and fatty acids?

Answer 22

Ketogenic amino acids (but cannot enter gluconeogenesis)

Question 23

how are fatty acids used but the brain and muscles?

Answer 23

→ ketone bodies

Question 24

can fatty acids be used in gluconeogenesis?

Answer 24

no

Question 25

what happens physically when the demand for ATP increases in muscles (aerobic)?

Answer 25

as O2 is still available → increase number of glucose transported on muscle cell membranes

Question 26

what is adrenalin’s role in meeting the ATP demand (aerobic)?

Answer 26

1) muscle glycolysis incr.
2) liver gluconeogenesis incr.
3) incr. fatty acid release from adipocytes

Question 27

what happens in muscles when the ATP demands cannot be met by oxidative phosphorylation (anaerobic)?

Answer 27

1) muscle glycogen breakdown increases

2) pyruvate -(LDH)→ lactate

Question 28

what happens to lactate when the muscles are recovering afrter anaerobic exercise?

Answer 28

1) lactase -(LDH)→ pyruvate (reversible)

2) pyruvate enters gluconeogenesis pathway to form glucose

Question 29

what are two ways in which metabolic pathways can be controlled?

Answer 29

• product inhibition

- signalling molecules e.g. hormones

Question 30

how do you compare the relative activities of enzymes?

Answer 30

using Michaelis Constant (KM) which is the concentration of substrate at which the enzyme functions at a half-maximal rate

Question 31

what is the difference between the hexokinase found in the liver and the muscle?

Answer 31

glucose → g-6-p

muscle:

1) active at low concentrations (high glucose affinity)
2) highly sensitive to g-6-p inhibition so that when rate of glycolysis slows hexokinase is inhibited by high levels of g-6-p.

Question 32

where is glucose-6-phosphate found?

Answer 32

liver but not muscle

g-6-p → glucose

Question 33

which hormones control blood glucose levels?

Answer 33

• insulin
• glucagon
• adrenaline
• glucocorticoids (incr. synthesis of metabolic reaction involved in glucose availability)

Question 34

what is the role of insulin in controlling blood-glucose?

Answer 34

REMOVAL OF GLUCOSE

1) incr. glucose uptake in liver → glycogen + glycolysis (aCoA → fatty acids)
2) incr. glycogen synthesis in muscles
3) incr. triglyceride synthesis in adipose tissues
4) incr. metabolic intermediates

Question 35

what is the role of glucagon in controlling blood-glucose?

Answer 35

RELEASE OF GLUCOSE (rem: where has all the glucose gone)

1) utilise of fatty acids → substrate to synthesise atp to preserve glucose for the brain
2) gluconeogenesis
2) glycogenolysis

Question 36

what happens when there is prolonged fasting?

Answer 36

no more glycogen reserves

1) incr. glucagon secretion
2) hydrolysation of triglycerides to fatty acids → metabolism
3) TCA cycle intermediates reduced → used for gluconeogenesis
4. Protein breakdown → glucogenic a-a for gluconeogenesis
5. Ketone bodies produced from fatty acids for brain substitute of glucose

Question 37

what are the complications for diabetes type I and II?

Answer 37

1) Hypoglycaemia if insulin dosage too high
2) Hyperglycaemia
3) Incr. ketone bodies → acidosis
4) Incr. fatty acids + lipoproteins → cardiovascular complications

Question 38

what is the difference between type I and type II diabetes?

Answer 38

type I → fail to secrete enough insulin (beta cell dysfunction)

type II → insulin resistance (ie insulin not ‘recognised?’ by cells in liver etc..

Question 39

what is hyperglycaemia?

Answer 39

too much glucose

Question 40

what is hypoglycaemia?

Answer 40

not enough glucose