Control of Metabolic Pathways Flashcards
What blood glucose concentration is normal?
4.0-5.5mM/litre
Where is the control of metabolic pathways typically centered around?
Irreversible reactions.
At irreversible reactions, what happens to the rate of the downstream steps if I increase the rate of enzyme activity.
What is the significance of this?
Greatly increased therefore it is desirable to have these irreversible steps as early in the pathway as possible (e.g. glucose conversion into glucose-6-phosphate as the first step of glycolysis).
Hexokinase catalyzes the first irreversible step in glycolysis. What is the name for different forms of the same enzyme and what two tissues have different forms of hexokinase?
Isoforms.
The liver and muscle cells have different isoforms of hexokinase.
What is the Michaelis constant/Km and how does it relate to VMax?
The concentration of a substrate at which an enzyme functions at half its maximal rate (VMax).
What are the two major ways we can control metabolic pathways?
Product Inhibition.
Signalling molecules such as hormones.
Will the KM of hexokinase I (found in the muscle) be higher or lower than the KM of hexokinase II (found in the liver) and why?
Higher as muscles often need lots of ATP for movement whereas the liver generally works at a constant, lower energy level and is needed to store glucose (if it had a high KM it would end up using all the glucose it got rather than storing it).
Will hexokinase I (muscle) be more or less sensitive to product inhibition (glucose-6-phosphate) than hexokinase II (liver).
More sensitive.
If the hexokinase II was more sensitive the liver would not only breakdown very little glucose due to its low KM but also would be slowed further by-product inhibition, making glycolysis too slow.
In addition, this means that under anaerobic conditions when the TCA cycle and so glycolysis slows, hexokinase is inhibited by accumulating levels of G-6-P (making more won’t help if the TCA cycle still has lots of G-6-P to break down).
Glucose-6-phosphate can catalyze the reverse reaction to hexokinase in what cells?
In the muscle but not the liver so that excess G-6-P that was made but not used in muscle contraction (in vigorous exercise) can be converted back for use later.
What does insulin do?
Increased glucose uptake by the liver used for glycogen synthesis and glycolysis (acetyl CoA produced is used for fatty acids synthesis).
Increased glucose uptake and glycogen synthesis in muscle.
Increased triglyceride synthesis in adipose tissue.
Increased usage of metabolic intermediates due to a general stimulatory effect on the body’s synthesis and growth
What does glucagon do?
It stimulates the production of glucose by gluconeogenesis and breakdown of glycogen and fat.
What secretes insulin and glucagon cells?
Islet cells of the pancreas.
What are glucocorticoids?
Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability.
After a meal blood glucose levels start to fall. What do cells start to use more for ATP?
Fatty acids so that glucose is preserved for the brain.
What happens after prolonged fasting?
Glucagon, adipose, TCA intermediates, proteins, ketones
Glucagon : insulin ratio increases further
Adipose tissue begins to hydrolyse triglyceride to provide fatty acids for metabolism
TCA cycle intermediates are reduced in amount to provide substrate for gluconeogenesis.
Protein breakdown provides amino acid substrates for gluconeogenesis.
Ketone bodies are produced from fatty acids and amino acids in the liver to substitute partially the brain’s requirement for glucose.
