Week 1- Intergration of Metabolism Flashcards
Describe the metabolic features of skeletal muscle
Can oxidize both fatty acids and carbohydrates, high ATP requirement during activity, during light contraction ATP is supplied by oxidative phosphorylation and during high contraction ATP is supplied by glycogen stores
Describe the metabolic features of the brain
Continuously requires ATP, cannot metabolise fatty acids, too much sugar (hyperglycemia) causes irreversible damage, too little sugar (hypoglycemia) causes coma, ketone bodies can be temporarily substituted for glucose as a metabolite
Describe the metabolic features of the heart
Continuously requires ATP, can oxidize both fatty acids and sugars, only aerobic respiration, uses TCA cycle substrates eg fatty acids and ketone bodies
Describe the metabolic features of the liver
Undertakes lots of metabolic processes eg gluconeogensis, glycogenlysis etc, maintains blood glucose at 4/5.5 mM, plays a key role in lipoprotein metabolism (triglycerides and cholesterol)
What can the body do when blood glucose falls below 3mM
Breakdown glycogen stores in liver, release fatty acids from adipose tissue, convert acetyl coA to ketone bodies, and eventually gluconeogenesis
Describe the process of gluconeogenesis
Pyruvate (3C) goes to oxaloacetate (4C) via pyruvate decarboxylase
Oxaloaceteate goes to phosphophenol pyruvate (4C) via phosphophenol pyruvate carboxylique kinase
Phosphophenol pyruvate goes to G3P (3C) NOTE: G3P comes from DHAP
G3P goes to fructose 1,6 bisphosphate (6C)
Fructose 1,6 bisphosphate goes to fructose 6 phosphate (6C) via fructose 1,6 bisphosphotase
Fructose 6 phosphate goes to glucose 6 phosphate (6C)
Glucose 6 phosphate goes to glucose (6C) via glucose 6 phosphatage
For gluconeogenesis where does pyruvate come from
From lactate that’s converted to pyruvate after anaerobic respiration
For gluconeogenesis where does oxaloacetate come from?
From some amino acids that come from the diet or skeletal muscle breakdown
For gluconeogenesis where does DHAP (that makes G3P) come from?
From glycerol (arising from triglyceride hydrolysis)
Where does gluconeogenesis take place?
1st reaction (pyruvate to oxaloacetate) in the mitchondria, rest of the process in the cytosol
What are glucogenic amino acids?
Amino acids that can be converted to glucose via gluconeogenesis
What are ketogenic amino acids?
Amino acids that give rise to skeletal bodies that can be made to ketones or fatty acids
Can fatty acids be converted to glucose? Explain why
No because 2C enter TCA cycle as CoA and 2 leave as CO2 so fatty acids can instead be converted to ketone bodies and used by the muscle/brain
How is rising demand for ATP met by muscles during aerobic respiration?
Increased number of glucose transporters on muscle cell membranes
Release of adrenaline which increases rates of glycolysis, gluconeogensis and release of fatty acids in adipose tissues
What happens during anaerobic respiration?
Glycogen is muscles is brocken down to give glucose
Pyruvate is converted to lactate via lactate dehydrogenase in order to replenish NAD+, lactate can then be used by the liver to generate glucose via gluconeogenesis
How are metabolic pathways usually controlled?
By an irreversible step that greatly increases the activity of an enzyme (for more control it is advantageous that this step is at the beginning of the reaction pathway)
How is glucose metabolism different in the muscle vs the liver?
Muscle: enzyme hexokinase I (catalyses the first irreversible step of glycolysis) has a km of 0.1 mM (normal blood glucose is 4mM) therefore always works at max velocity. When TCA cycle slows and glucose 6 phosphate builds up it can inhibit the enzyme
Liver: enzyme hexokinase IV has a km of 4mM therefore is largely unaffected by variation in blood glucose, also cannot be inhibited by glucose 6 phosphate
NOTE- liver also has the enzyme glucose 6 phosphotase which can form glucose from glucose 6 phosphate which skeletal muscles don’t have.
*hexokinase I and hexokinase IV are isomers of the enzyme hexokinase
Name the 4 hormones involved in controlling blood glucose and describe their functions
Insulin- lowers blood glucose
Glucagon- raises blood glucose
Adrenaline- mobilises glucose for the fight or flight response
Glucocorticoids- steroid hormone that increases the synthesis of enzymes associated with glucose availability
Describe the control of blood glucose after a meal (when there is high blood sugar)
Pancreas: secretes insulin
Liver: synthesis of glycogen and increased glycolysis
Muscles: synthesis of glycogen and glucose uptake by more transporters in membranes
Adipose tissue: synthesis of triglycerides
Describe the control of blood glucose when blood glucose is low
Pancreas: secretes glucagon from islets
Liver: breakdown of glycogen and gluconeogensis
Adipose tissue: breakdown of triglycerides for use as substrates in ATP production to preserve glucose for the brain
Describe the control of blood glucose when the body enters a state of starvation
Pancreas: secretes more and more glucagon
All cells: TCA cycle substrates are reduced and protein is brocken down to give amino acids for substrates for gluconeogenesis
Brain: ketone bodies substitue short term for the lack of glucose
Adipose tissue: brocken down to allow release of fatty acids
What does diabetes result in?
The body thinking it’s in a state of starvation (causing response for maintenance of blood glucose during starvation) when starvation is not occurring
What happens in type 1 diabetes?
The body fails to secrete insulin due to beta cell dysfunction in the pancreas
What happens in type 2 diabetes?
The body fails to respond to insulin secretion
What are complications associated with diabetes mellites?
Hypoglycemia: coma
Hyperglycemia: permanent damage of extremities eg retina, nerves and kidneys
Increase in fatty acids: heart problems
Increase in ketone bodies: risk of acidosis
