Metabolic Integration Flashcards
Which FOUR reaction pathways covered in BIOL244 lectures are anabolic?
- Gluconeogenesis
- Glycogen biosynthesis
- Lipid biosynthesis (fatty acid biosynthesis)
- Amino acid biosynthesis
Which FOUR reaction pathways covered in BIOL244 lectures are catabolic?
- Glycolysis
- The TCA cycle (and ultimately oxidative phosphorylation)
- β-oxidation (of fatty acids / lipid degredation)
- Amino acid catabolism
The pentose phosphate pathway is also included but not covered.
List:
FOUR key hub metabolites that link the major pathways covered in BIOL244.
- 4 sugar-phosphates
- 3 α-ketoacids
- 2 CoA derivatives
- PEP (phosphoenolpyruvate)
Define:
Evolved coupling stoichiometry
The number of ATP molecules consumed/produced in a particular pathway.
A compromise, and consequence of evolution.
Define:
Obligate coupling stoichiometry
The stoichiometric coupling of redox reactions with electron carriers.
What changes about the ΔG° of pathways that generate more ATP than the evolved coupling stoichiometry.
They have progressively smaller negative ΔG° values overall, making them less and less thermodynamically favourable.
The evolved coupling stoichiometric amount of 38 (in prokaryotic cells) provides a high yield per glucose molecule, whilst still being low enough that almost all glucose is metabolised.
The overall thermodynamic efficiency of any metabolic sequence is determined by…
…ATP coupling.
The involvement of ATP alters the ΔG of the reaction.
What helps ensure the [ATP] : [ADP] + [Pi] ratio stays high?
Kinetic controls over metabolic pathways.
Which allows ATP hydrolysis to power essentially any biochemical process.
What role does ATP serve as an allosteric effector?
Its concentration acts as an energy status index for the cell, and determines the rates of key allosterically-regulated enzymes at important points in metabolic pathways.
What is the stoichiometric role of ATP?
Establishing large equilibrium constants for metabolic conversions, and thus rendering them thermodynamically favourable.
As this, it acts as the energy currency of the cell.
What is the adenylate system/pool comprised of?
ATP, ADP, & AMP.
What “lies at the very heart of metabolism”?
Energy transduction and energy storage in the adenylate
system (pool).
This is ATP, ADP, and AMP.
Which enzyme provides a direct connection amongst the three molecules of the adenylate pool?
(ATP, ADP, and AMP)
Adenylate kinase
It catalyses the reversible phosphorylation of AMP by ATP.
ATP + AMP ⇌ 2ADP
How many phosphoanhydride bonds does ATP have?
2
How many phosphoanhydride bonds does ADP have?
1
How many phosphoanhydride bonds does AMP have?
0
What happens to the energy charge if [ATP] is high?
It approaches 1.
What happens to the energy charge if [ATP] is low?
It approaches 0.
How does energy charge affect metabolic regulation?
It contributes to the regulation of key enzymes.
(e.g. phosphofructokinase being allosterically inhibited by high concentrations of ATP, but stimulated by AMP).
What is considered the cellular energy sensor?
AMP-activated protein kinase (AMPK)
What happens when AMP binds to AMPK?
Its activity increases significantly.
More than 1000-fold!
AMP is its allosteric activator and promotes phosphorylation (activation).
What happens when ATP binds to AMPK?
It promotes dephosphorylation and thus renders AMPK inactive.
What happens when ADP binds to AMPK?
It protects AMPK from dephosphorylation.
What is the function of AMPK in its active form?
It phosphorylates many protein targets controlling cellular energy production and consumption.
List:
The THREE major fuel depots in animals.
- Glycogen (liver & muscle)
- Triglycerides (adipose tissue)
- Protein (mostly skeletal muscle)
This is also the order for preference of use of these different energy stores.
What is the major energy reservoir of the brain?
Nothing
This is why the brain consumes the most energy of all our organs.
What is the major energy reservoir of the skeletal muscle (resting state)?
Glycogen
What is the major energy reservoir of the skeletal muscle (strenuous activity)?
Nothing
This is when all of the energy stores have been consumed.
What is the major energy reservoir of the heart muscle?
Glycogen
What is the major energy reservoir of adipose tissue?
Triacylglycerols
(aka triglycerides)
What are the TWO major energy reservoirs of the liver?
Glycogen & triacylglycerols
What is the preferred substrate of the brain?
Glucose
But during starvation it can utilise ketone bodies.
What is the preferred substrate of the skeletal muscle (resting state)?
Fatty acids
What is the preferred substrate of the skeletal muscle (strenuous activity)?
Glucose from glycogen.
What is the preferred substrate of the heart muscle?
Fatty acids
What is the preferred substrate of adipose tissue?
Fatty acids
What are the THREE preferred substrate of the liver?
- Amino acids
- Glucose
- Fatty acids
What energy sources are exported from the brain?
None
What energy sources are exported from the skeletal muscle (resting state)?
None
What energy sources are exported from the skeletal muscle (strenuous activity)?
Lactate
What energy sources are exported from the heart muscle?
None
What TWO energy sources are exported from adipose tissue?
Fatty acids & glycerol
What THREE energy sources are exported from the liver?
- Fatty acids
- Glucose
- Ketone bodies
What is the major metabolic processing centre in vertebrates?
The liver.
What hub metabolite does the activity of the liver centre around?
Glucose-6-phosphate
What are the FIVE key fates of glucose-6-phosphate in the liver?
- Converted to glycogen.
- Released as blood glucose.
- Used to **generate NADPH **and pentoses via the pentose phosphate
pathway. - Catabolized to acetyl-CoA for fatty acid synthesis.
- Energy production by oxidative phosphorylation.
