Metabolic Homeostasis Flashcards
What are the two requirements the Metabolism must meet
- Synthesise that not provided by diet
- Protect our internal environment from toxins & changing external conditions
What are the four basic types of metabolic pathway
- Fuel oxidative pathways
- Fuel storage & mobilisation
- Biosynthesis pathways
- Detoxification/waste disposal pathways
What is considered to be the ‘Anabolic’ pathway
Synthesis of large molecules
(e.g. biosynthesis & fuel storage pathways)
What is consider to be the ‘Catabolic’ pathways
Breakdown of large molecules
(e.g. fuel oxidation pathways)
The control of the balance between substrate availability and need, manifested by anabolic vs catabolic pathways, is known as
Metabolic Homeostasis
Main body tissues (e.g. brain, RBC, kidney medulla, skeletal muscle) require glucose
Therefore what is the normal concentration of glucose in the blood
80-100 mg/dL
A significant decrease in glucose concentration (<60 mg/dL) will result in
limited brain metabolism
Hypoglycemia
(Glucose influx lowers due to low Km of brain-blood barriers)
If there is a significant increase in blood glucose….
- There are hyperosmolar effectos = neurological deficits & possible coma
- Non-enzymatic glycoslation of proteins
The balance between use, release, storage by different tissues is achieved in 3 ways
What are they?
- Blood (nutrients)
- Hormones
- Central Nervous system
What is the major anabolic hormone
Insulin
Around 80 mg/dL is considered the release threshold for insulin
Where is it released from
Released from β-cells of islets of Langerhans (pancreas)
What tissues/organs will degrade insulin
- Liver
- Kidney
- Skeletal muscle
How does glucose stimulate insulin to be released
What is the process behind this
- At a high conc of glucose, the GLUT-2 transporter will transport glucose into β-cells
- Here it will become phosphorylated glucokinase forming glucose-6-phosphate (trapping glycose in the cell)
- Causes metabolism within the cell to increase, producing ATP, which will inhibit K⁺ channel
- This causes membrane polarisation and Ca²⁺ will move into cell
- Vesicles containing insulin, will fuse with outer membrane, releasing insulin into blood
What is the name of the most important ‘contra-insular’ hormone of metbolism control
Glucagon
Where is glucagon released from
α-cells of pancreas
Where does Glucagon act upon
Liver and adipose tissue
Secretion of Glucagon is regulated by
Glucose & Insulin
Levels of glucagon build as both fall
The secretion of Glucagon promotes
Glucose production (fuel mobilisation)
* via glycogenolysis
* via gluconeogenesis
Both insulin and glucagon bind to receptors on a cell’s surface
This causes
Initiate intracellular signaling cascades
Can lead to covalent modification/allosteric regulation of enzymes
Affect enzyme gene transcription
Insulin will ……….. cell receptor
Autophosphorylates
Glucagon binding causes …..
2nd messenger formation
There are two temportal controls seen for these enzymes, what are they?
- Minutes-hours: changes in enzyme catalytic activity/kinetics
- Hours-Days: regulation of enzyme synthesis
The absorptive state is known as ….
What will it involve
The ‘well-fed’ state (in the 2-4hrs period after a normal meal)
Involve elevated insulin-to-glucagon ratio, with lots of readily available substrates - hence an ‘anabolic state’
Once insulin is stimulated in the well-fed state, what will then occur
- Increased glucose uptake by Hepatocytes (with insulin dependent gluocse transporters)
- Increased phosphorylation of glucose - using glucokinase forming glucose-6-phosphate
- Converted into glycogen by glycogen synthase (allosterically regulated)
- Increased activity of Pentose Phosphate pathway forming NADPH
- Leads to high amounts of glycolysis
What happens to Fatty Acid synthesis during the absorptive state
Fatty acid synthesis at the liver increases during the absorptive state due to acetyl CoA & NADPH availability
As well as Acetyl CoA Carboxylase being activated
What happens to Triacylglyercol synthesis during the absorptive state
Increased Triacylglycerol synthesis
Due to increased acyl CoA presence & also due to hydrolysis of TAG component from chylomicrons
If amino acids are not used for protein synthesis in the liver which is increased in the absorptive state, what happens to them
They are exported to other tissue for use or degradation (deamination)
Carbon skeleton degraded to pyruvate and TCA intermediates
If no food is taken in after the end of the Absorptive state (~4hrs post food) we enter the …….
Fasting state
What happens to glucose, amino acid and TAG levels during the fasting state
Levels fall
What happens to hormone levels during the fasting state
Insulin decreases
Glucagon and Adrenaline increase
The fasting state is therefore an….
‘Catabolic state’
The main role of the fasting state is to maintain plasma glucose levels
How is this done?
- Inter-tissue exchange of compoents
- Mobilisation of fatty acids from adipose tissue & ketone bodies from liver to supply energy to other tissue
The flow of intermediates through the metabolic pathways is controlled by
- Substrate availibility
- Allosteric regulation of enzymes
- Covalent modification of enzymes
- Induction-repression of enzyme synthesis
During the fasting state, most enzymes used in the Absorptive state are now
Phosphorylated and inactive
What 3 enzymes are highly active within the fasting state
- Glycogen phosphorylase
- Glycogen phosphorylase kinase
- Hormone-sensitive lipase
What two processes occur within the fasting state
- Glycogenolysis (releasing glucose) + gluconeogenesis
- Lipolysis (releasing FA’s & glycerol)
The carbon skeletons from gluconeogenesis are derived from
Glucogenic amino acids
lactate from muscle
Glycerol from adipose tissue
Fatty acid oxidation is the major energy source in liver tissue
Where does this occur
Adipose tissue
Fat metabolism can also influence gluconeogeneis through activiting different hormones
Ketone body synthesis occurs outside the liver
What is the hypercatabolic state
Extreme states of catabolic activity occur with injury (e.g. burns & septic stress)
Mobilise body protein, fat & carbohydrates from bodily stores and negative nitrogen balance (skeletal muscle degradation)
Patients may become hyperglycemic
What is the main mediator of the hypercatabolic state
Cortisol
* Encourages ubiquitin-mediated proteolysis and induced glutamine synthase
During the hypercatabolic state amino acids are used in a …..
Prioritised fashion
