MBC - Integration of Metabolism Flashcards
What does the muscle use for ATP supply during light contraction?
Relies on oxidative phosphorylation
What does the muscle do when contraction becomes more vigorous?
Relies on the breakdown of glycogen stores
What is broken down during anaerobic conditions?
pyruvate is broken down into lactate via LDH
Where does lactate go once produced in muscles?
the liver
What does the brain constantly require?
Glucose
What can the brain not metabolise?
Fatty acids
What can partially substitute for glucose in the brain?
Ketone bodies
What is caused by hypoglycaemia?
Faintness/coma
What is caused by hyperglycaemia?
Irreversible damage especially to nerve rich cells such as the retina.
What are myocytes designed for?
Aerobic respiration
How are myocytes ideal for aerobic respiration?
Rich in mitochondria Utilise TCA substrates such as free fatty acids and ketone bodies.
What happens when energy demand in the heart exceeds energy supply?
Loss of oxygen leads to cell death and myocardial infarction
What is the role of the liver?
Highly metabolically active: - interconverts nutrient types - central role in maintaining blood glucose levels - stores glucose as glycogen - Lipoprotein metabolism - key in triglyceride/cholesterol transport
What is the level of glucose that the liver tries to maintain?
4.0-5.5 mM
What is the first step of carbohydrate metabolism?
Carbohydrate is tier broken down into glucose or other simple sugars
What happens to glucose after being formed by carbohydrates?
It is broken down into glucose-6-phosphate via hexokinase
What happens to simple sugars after being formed from carbohydrates?
they are converted to glucose-6-phosphate
What happens to glucose-6-phosphate?
Either becomes pyruvate. Excess glucose-6-phosphate will become glycogen, or it can enter pentose phosphate pathway to generate nucleotides, and NADPH for anabolic reactions e.g. cholesterol synthesis
What happens to pyruvate?
Can either become acetyl-CoA, or backbone can be used for amino acids to become nucleotides, or can become lactate in anaerobic conditions.
What happens to acetyl-CoA?
Can enter TCA cycle, or can become fatty acids/cholesterol if in excess, or ketone bodies in conditions of starvation.
What happens in the TCA cycle?
Oxidation of small molecules and subsequent oxidative phosphorylation, or some products can become amino acids and subsequently nucleotides.
How does the body avoid hypoglycaemia in the short term?
Breakdown of glycogen stores Release of free fatty acids from adipose tissue Convert acetyl-CoA to ketone bodies in the liver
How long can the body resist hypoglycaemia for?
12-18 hours
What does the body do after 12-18 hours of resisting hypoglycaemia?
Uses gluconeogenesis to generate glucose form pyruvate/oxaloacetate
What is the first step of gluconeogenesis?
Pyruvate is converted to oxaloacetate via pyruvate carboxylase
Where does the conversion of pyruvate to oxaloacetate occur?
Mitochondria
Where does gluconeogenesis primarily occur?
Cytoplasm
What are the irreversible reactions from glycolysis and how do we bypass them?
Reactions involving kinases from glycolysis We bypass them by using phosphatases
What is the second step of gluconeogenesis?
Oxaloacetate is converted to phosphoneolpyruvate via phosphoenolpyruvate carboxykinase
What is the third step of gluconeogenesis?
Phosphoenolpyruvate is converted to fructose-1,6-bisphosphate
What is the fourth step of gluconeogenesis?
fructose-1,6-bisphosphate is converted to fructose-6-phosphate via fructose-1,6-bisphosphatase.
What is the fifth step of gluconeogenesis?
Fructose-6-phosphate is converted to glucose-6-phosphate
What is the sixth and final step of gluconeogenesis?
Glucose-6-phosphate is converted to glucose via glucose-6-phosphatase.
At what level of glucose is a hypoglycaemic coma induced?
Below 3mM of glucose.
How do proteins contribute to gluconeogenesis?
Degradation of all 20 amino acids leads to 7 products. Glucogenic amino acids have skeletons which give rise to glucose via gluconeogenesis.
How do proteins contribute to fatty acid/ketone body formation?
Ketogenic amino acids have skeletons which can be used for fatty acid synthesis or ketogenesis.
How do fatty acids contribute to glucose metabolism?
Can’t be converted into glucose however can be converted into ketone bodies thus metabolised by tissues e.g. muscle and brain.
How does glycerol contribute to glucose metabolism?
Glycerol can be converted into DHAP which can be used in the gluconeogenic pathway upstream.
What is typically the main focus for controlling metabolic reactions?
Irreversible reactions
When is the greatest level of control achieved? Give an example
Greatest level of control is achieved when control steps e.g. inhibition, are placed early in the downstream pathway. For example, hexokinase is inhibited easily by G-6-P, therefore in anaerobic conditions, G-6-P builds up and hexokinase is inhibited early.
What happens in aerobic exercise?
Contractions increase ATP demand Contractions increase glucose transport into muscle
How does the body respond to aerobic exercise?
Increase in glucose transporters in myocyte membranes. Adrenalin increases muscle glycolysis Adrenalin increases fatty acid release from adipocytes Adrenalin increases gluconeogenesis in the liver.
What happens in anaerobic exercise?
ATP demand cannot be matched by O2 delivery Glucose transport (supply) cannot match demand
How does the body respond to anaerobic exercise?
Muscle glycogenolysis increases Pyruvate is broken down into lactate + H+. Liver then uses lactate to form pyruvate and thus generate glucose via gluconeogenesis (pyruvate to lactate is a reversible reaction with the oxidation of NADH to NAD+)
What can control steps be in the form of?
Product inhibition Signal influence e.g. hormones
What is Michaelis constant (Km)?
The concentration at which an enzyme functions at half of its maximal rate (half of Vmax)
Explain the difference in hexokinase Km between liver and muscle
There are different hexokinase isoforms in the liver and muscle. In the muscle, HK1 has Km of 0.1mM whereas in the liver, HKIV has Km of 4.0mM.
Explain the significance of a low Km in muscle.
This means that hexokinase in the muscle undergoes glycolysis readily as it is sensitive to glucose. It is also inhibited easily by G-6-P due to its high sensitivity.
Explain the significance of a high Km in the liver.
This means that hexokinase IV is less active and less sensitive to glucose levels and G-6-P levels, therefore less easily inhibited.
What enzyme is present in the liver but not the muscle?
Glucose-6-phosphatase (for gluconeogenesis)
What is the role of insulin?
Reduces blood sugar levels: - Increases glucose uptake by liver and cells - Increases synthesis of fats and proteins - Increases storage of glucose as glycogen and fat.
What is the role of glucagon?
Increases blood sugar levels: - Increases HGO - Increases lipolysis and ketogenesis - Increases glycogenolysis
What is the role of adrenalin?
Rapidly mobilises glucose for a fight or flight response
What is the role of glucocorticoids?
Steroid hormones that increase the synthesis of enzymes concerned with glucose availability.
What happens on having a meal to hormone levels?
Insulin rises to counteract the quick rise in glucose in the blood, glucagon falls. - Increased glucose uptake by liver and muscle for glycogen synthesis. - Increased glycolysis by liver (acetyl CoA is used for fatty acid synthesis). - Increased triglyceride synthesis in adipose tissue - Increased usage of metabolic intermediates due to general stimulatory effect and growth.
What happens after having a meal?
Glucose levels start to fall so is controlled by: - Increased glucagon and reduced insulin for islets. - HGO increases from glycogen breakdown and gluconeogenesis - Lipolysis used as alternative substrate for ATP production. - Similar effects to adrenalin
What are the effects of adrenalin?
Similar to that of glucagon, but adrenalin also stimulates glycolysis and glycogen breakdown in skeletal muscle, and lipolysis in adipose tissue.
What happens during prolonged fasting to the glucagon:insulin ratio?
increases further
What happens during prolonged fasting to adipose tissue?
Lipolysis increases for metabolism
What happens during prolonged fasting to the TCA cycle?
Intermediates for TCA are reduced to provide substrates for gluconeogenesis.
What happens during prolonged fasting to proteins?
Proteolysis increases to provide amino acid substrates for gluconeogenesis
What happens during prolonged fasting to ketone bodies?
Ketogenesis arises from fatty acids and amino acids to partially substitute for glucose in the brain.
