MBC - Integration of Metabolism Flashcards
What can’t the brain metabolise?
Fatty acids
What is the condition name for too little glucose?
Hypoglycaemia
What is the condition name for too much glucose?
Hyperglycaemia
What can hypoglycaemia cause?
Faintness & Coma
What can hyperglycaemia cause?
Irreversible damage to tissues rich in nerve (eg retina)
What happens when O2 becomes a limiting factor?
Glycogen breakdown
Lactate form
Where does lactate go after being formed?
Leave muscle into liver via blood
What can be used as fuel for OxPhos?
Oxygen, glucose, fatty acid
What attribute to heart working constantly?
Utilises TCA cycle substrates (free fatty acid, ketone bodies)
Why is loss of O2 supply to heart devastating?
Heart is designed completely for aerobic respiration
Rich in mitochondria
What happens when there is no oxygen supply to the heart?
Cell death, myocardial infarction (Energy demand > supply)
What is the role of the liver?
WIDE REPERTOIRE of METABOLIC PROCESSES:
- Intermediate recipient of nutrient from intestines
- Maintain blood glucose lv.
- Glucose storage (as glycogen)
- Lipoprotein metabolism (transport of triglycerides & cholesterol)
- Produces ketone bodies
- Produces bile for emulsification
- Glycolysis
- Transamination
- Gluconeogenesis
What is adipose tissue?
Fat - storage tissue for fatty acid in form of triglycerides
What is the aim of gluconeogenesis?
Generate glucose from pyruvate
When is gluconeogenesis needed?
During fasting or starvation (decrease in blood glucose lv.)
What does the body do to avoid hypoglycaemia coma?
Breakdown liver glycogen (used by brain)
Release free fatty acid from adipose tissue (muscle)
Convert Acetyl CoA into ketone bodies via liver (muscle)
When and where is lactate generated?
When rate of glycolysis > rate of TCA & ETC
In the skeletal muscle
Where are amino acids derived from?
Breakdown of skeletal muscle
What is used to generate DHAP?
Glycerol backbone from triglyceride hydrolysis
How many reactions need to be bypassed in gluconeogenesis?
4, with 4 enzymes needed to turn energetically favourable
Why do we need to bypass the reaction?
Because there are 3 irreversible reactions catalysed by hexokinase, phosphofructokinase, pyruvate kinase
Where does excess glucose-6-phosphate go?
Stored as glycogen in liver or muscle
What does Acetyl CoA do during fasting?
Turn into ketone bodies
Where does excess Acetyl CoA go?
Turn into fatty acid, cholesterol etc. and stored as triglycerides in adipose tissue
What does glucogenic do as a fuel source?
Store in skeleton turn into glucose in gluconeogenesis
What does ketogenic do as a fuel source?
Synthesises fatty acid + ketone bodies
No gluconeogenesis
What does triglyceride do as a fuel source?
Breakdown into fatty acid & glycerol
- Fatty acid produces ketone bodies (used by muscle & brain)
- Glycerol backbone used to generate DHAP
How to we access the greatest level of control with metabolic pathways?
“Irreversible step” catalysed by enzyme needs to be early in the pathway
How do we compare the activities of the different enzymes at different concentrations of substrate?
Michaelis constant (K_M)
- The concentration of substrate at which enzyme function at half-maximal rate (V_MAX)
What isoform of hexokinase are at muscle and liver?
Hexokinase I (muscle)
Hexokinase IV (liver)
Is muscle Hk high or low glucose affinity?
High
Is liver Hk high or low glucose affinity?
Low
What does it mean if muscle Hk I is high glucose affinity (K_M of 0.1mM) ?
It is active at low glucose conc. - therefore active at MAX velocity at all times
What happens to muscle Hk I under anaerobic conditions?
Due to TCA rate dropping and glycolysis slowing, Hk I is inhibited by the increase level of glucose-6-phosphate
Where is glucose-6-phosphatase found & what does it do?
Liver only - it can catalyse reverse reaction to hexokinase
generate glucose from glucose-6-phosphate
Under aerobic conditions, how are energy demands met?
OxPhos –> ATP
eg muscle contract more, require actomyosin ATPase & cation balance (Ca2+/Na+k+ATPase)
- increase in glucose transporters on membranes of muscle cell
In the case of adrenaline under aerobic conditions, what would happen?
Increase rate of glycolysis in muscle
Increase rate of gluconeogenesis in liver
Increase release of fatty acid from adipose
Under anaerobic conditions, how can energy demands be met?
Glycogen within muscle breakdown
Pyruvate taken up by liver, replenish NAD+ & maintain glycolysis
Pyruvate –> lactate (lactate dehydrogenase)
Lactate is used by liver to generate glucose (Gluconeogenesis)
What are the 4 hormones that control blood glucose level?
Insulin, Glucagon, Adrenaline (epinephrine), Glucocorticoids
Where are insulin and glucagon produced?
Islet of Langerhans in the pancreas
What does insulin do?
Stimulate uptake of glucose, store as glycogen & fat
What does glucagon do?
Stimulate production of glucose (Gluconeogenesis), breakdown of glycogen & fat
What does Adrenaline do?
Mobilise glucose for “Fight or flight”
What does glucocorticoids do?
Increase synthesis of metabolic enzymes (glucose availability)
What happens when glucagon lv. increases and insulin lv. reduces?
Gluconeogenesis
Fatty acid breakdown as alternative for ATP production (In order to preserve glucose for brain)
What happen in prolonged fasting? (No glycogen reserves)
Further increase in glucagon and decrease in insulin
- Adipose hydrolyse triglyceride to form fatty acid
- Reduce TCA intermediates & Protein breakdown to amino acid (substrate for gluconeogenesis)
- Fatty acid –> ketone bodies & amino acid in liver (substitute glucose for brain)
What are the two types of diabetes mellitus?
Type I - Beta cell dysfunction (don’t secrete enough insulin)
Type II - Insulin resistance (don’t respond to insulin)
What happens to metabolism if you have diabetes?
Goes into starvation mode (prolonged fasting)
What are the complications with diabetes?
- Hyperglycaemia & progressive tissue damage
- Increase plasma fatty acid + lipoprotein lv. (possible cardiovascular complications)
- Increase ketone bodies from liver (Risk of Acidosis)
- Hypoglycaemia (if insulin dosage no properly controlled –> coma)
How does glucagon protect against hypoglycaemia?
- Liver glucagon stimulate gluconeogenesis & glycogenolysis
- Insulin deficiency and excess glucagon –> increased hepatic output of glucose (hyperglycaemia)
In fasting state, what are the main metabolic fuel for Heart and Brain?
Heart - fatty acid
Brain - Glucose if available (ketone body)
Why is there an increase of glucose transporters on adipocytes when BGL increases?
To increase uptake to make triglycerides
Where are ketone bodies produced?
Liver
What increases oxaloacetate production?
Breakdown of amino acids
What molecules does glucagon increases the synthesis of glucose from?
Glycogen, glycerol, amino acids
What increases the synthesis of protein in a fed state?
Insulin
At what plasma glucose level induces unconsciousness?
=< 2mmoL
After a meal, the blood glucose concentration in the hepatic portal vein is high. What properties of Hexokinase IV allow a marked increase in production of hepatic of glucose 6-phosphate (G-6-P) in response to the increased portal glucose concentration?
The KM for Hexokinase IV is approximately 4mM
