Integration of metabolism Flashcards
what are the metabolic features of skeletal muscles?
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
what are the metabolic features of the brain?
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)
what are the metabolic features of the heart?
1) rich in mitochondria + completely aerobic mechanism
2) can oxidise fatty acids + carbs, ketone bodies
what are the metabolic features of the liver?
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
what are the metabolic features of adipose tissues?
long term energy store for fatty acids in the form of triglycerides
what can excess glucose-6-phosphate be used for if not in glycolysis?
to generate glycogen
what can excess Acetyl CoA be used for if not in the TCA cycle?
fatty acids (stored as triglycerides in adipose tissues), cholesterol
what happens to the Acetyl CoA in periods of fasting?
rather than enter the TCA cycle much of it is used in ketone body production
what happens to pyruvate in periods of extreme exercise when the muscles can’t respire anaerobically?
lactate is produced in anaerobic respiration
what can the intermediates of the tca cycle generate?
some amino acids
what can pyruvate be a source of?
some amino acids (therefore some nucleotides)
what happens to Glucose-6-phosphate via the pentose phosphate pathway?
It can be used as a source of nucleotide production
i.e. g-6-p → pentose phosphate → nucleotides
how does the body avoid hypoglycaemia in the short term?
(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
how does the body avoid hypoglycaemia in the long term?
gluconeogenesis (as otherwise all glucose will be exhausted by 12-18 hrs)
what are the steps involved in gluconeogenesis?
(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
how can lactate be used to generate pyruvate?
when rate of glycolysis > rate of TCA cycle + ETC
lactate –(lactate dehydrogenase)→ pyruvate
how can some G3P be generated?
triglycerides → glycerol (+ fatty acids) → DHAP → G3P
how is pyruvate converted to phosphoenolpyruvate in gluconeogensis?
1) pyruvate –(pyruvate carboxylase)→ oxaloacetate –mitochondria
2) oxaloacetate –(p..vate carboxykinase)→ phosphoenolpyruvate
how is fructose-1,6-bisP converted to fructose-6-p in gluconeogenesis?
fructose-1,6-bisphosphatase
how is glucose-6-P converted to glucose in glyconeogenesis?
glucose-6-phosphatase
which types of amino acids can be used in gluconeogenesis?
glucogenic a-a —- their skeletons can give rise to glucose via gluconeogenesis
which types of amino acids can be used to synthesise ketone bodies and fatty acids?
Ketogenic amino acids (but cannot enter gluconeogenesis)
how are fatty acids used but the brain and muscles?
→ ketone bodies
can fatty acids be used in gluconeogenesis?
no
what happens physically when the demand for ATP increases in muscles (aerobic)?
as O2 is still available → increase number of glucose transported on muscle cell membranes
what is adrenalin’s role in meeting the ATP demand (aerobic)?
1) muscle glycolysis incr.
2) liver gluconeogenesis incr.
3) incr. fatty acid release from adipocytes
what happens in muscles when the ATP demands cannot be met by oxidative phosphorylation (anaerobic)?
1) muscle glycogen breakdown increases
2) pyruvate -(LDH)→ lactate
what happens to lactate when the muscles are recovering afrter anaerobic exercise?
1) lactase -(LDH)→ pyruvate (reversible)
2) pyruvate enters gluconeogenesis pathway to form glucose
what are two ways in which metabolic pathways can be controlled?
- product inhibition
- signalling molecules e.g. hormones
how do you compare the relative activities of enzymes?
using Michaelis Constant (KM) which is the concentration of substrate at which the enzyme functions at a half-maximal rate
what is the difference between the hexokinase found in the liver and the muscle?
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.
where is glucose-6-phosphate found?
liver but not muscle
g-6-p → glucose
which hormones control blood glucose levels?
- insulin
- glucagon
- adrenaline
- glucocorticoids (incr. synthesis of metabolic reaction involved in glucose availability)
what is the role of insulin in controlling blood-glucose?
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
what is the role of glucagon in controlling blood-glucose?
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
what happens when there is prolonged fasting?
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
what are the complications for diabetes type I and II?
1) Hypoglycaemia if insulin dosage too high
2) Hyperglycaemia
3) Incr. ketone bodies → acidosis
4) Incr. fatty acids + lipoproteins → cardiovascular complications
what is the difference between type I and type II diabetes?
type I → fail to secrete enough insulin (beta cell dysfunction)
type II → insulin resistance (ie insulin not ‘recognised?’ by cells in liver etc..
what is hyperglycaemia?
too much glucose
what is hypoglycaemia?
not enough glucose
