Energy I: Metabolism, ATP, Glycolysis Flashcards
What are catabolic processes?
The breakdown of complex molecules to release energy
The breakdown of these produces precursors that can be used in anabolic processes
What are anabolic processes?
Synthesis of new molecules from less complex components
Why is glucose an important source of energy?
- ATP contains high energy phosphate bonds, and when these are broken, they release energy
- Glucose produces ATP when oxidised (as well as water and carbon dioxide)
It can also produce ATP in anaerobic conditions
How much ATP do we require?
At rest - 40Kg/24hr
During exercise - 0.5Kg/min
How does the body continue to meet the demands of ATP required?
Resynthesises ATP from ADP
What are the cofactors central to metabolism?
NAD - nicotinamide adenine dinucleotide
FAD - flavin adenine dinucleotide
These are electron carriers used for oxidation/reduction reactions
What is the form of oxidised NAD?
NAD+
What is the form of reduced NAD?
NADH + H+
What is the form of oxidised FAD?
FADH2
What are the 4 major oxidative pathways?
- Glycolysis
- Citric acid cycle
- Electron transport coupled to oxidative phosphorylation
- Fatty acid oxidation
What is glycolysis?
Splitting of 6 carbon glucose into 2X 3 carbon pyruvate molecules
What are the products of glycolysis?
- 2 X 3C pyruvate
- 2X NADH molecules
- 2X ATP molecules
Produces 2X the products due to the fact that glucose splits into 2 3C compounds, and therefore the reaction must happen twice
What is the first step of glycolysis?
Phosphorylation of glucose to form G-6-P (glucose six phosphate)
This results in the hydrolysis of ATP into ADP, as this phosphate will be the one that phosphorylates glucose
What are the 2 functions of G-6-P?
- Maintains glucose gradient (inside + outside cell)
- Traps glucose within cell, G-6-P is unable to be transported out of cell
What is G-6-P converted into?
Fructose 6 phosphate
What is Fructose 6 Phosphate converted into? What does this require?
Fructose 1,6 bisphosphate
This requires the hydrolysis of ATP into ADP, to provide the additional phosphate group for Fructose 1,6 bisphosphate
What does Fructose 1,6 bisphosphate split into?
A 3C molecule called Dihydroxyacetone (DHAP)
A 3C molecule called Glyceraldehyde 3 Phosphate (GAP)
These molecules are in equilibrium, but the equilibrium favours the production of GAP
What does GAP produce? What does this require?
Phosphoenol pyruvate
This requires the reduction of NAD+ into NADH, and synthesis of ATP from ADP
What does phosphoenol pyruvate produce?
What does this require?
Pyruvate (3C)
This requires the synthesis of ATP from ADP
What molecules regulate glycolysis?
How can these molecules be regulated?
- Enzymes, catalysing irreversible reactions are potential site for regulation
- Enzymes can be regulated by:
- Reversible binding of allosteric effectors
- Covalent modification (e.g. phosphorylation)
- Transcription (quantity of enzyme can be increased or decreased depending on gene expression)
Can be measured in terms of milliseconds, seconds, hours
What are the enzymes that regulate glycolysis?
- Hexokinase
- Phospho-fructokinase
- Pyruvate kinase - this enzyme exists in number of different forms, and these different forms are distributed in different tissues - This is almost only in the liver??
- Some organs such as the heart and brain do not have enzymes with allosteric binding sites, and so glycolysis would therefore not be regulated by pyruvate kinase
What does hexokinase do?
Regulates first step in glycolysis, conversion of glucose into G6P
What does phospho-fructokinase do?
Regulates conversion of Fructose 6 Phosphate into Fructose 1,6 bisphosphate
What does pyruvate kinase do?
Regulates conversion of phosphoenol pyruvate into pyruvate
Not all organs will use this though, as they don’t all have enzymes with allosteric binding sites
How is hexokinase activity regulated?
By G6P - will inhibit the further conversion of glucose to G6P, prevents too much glucose being fed through glycolytic pathway
How is phospho-fructokinase regulated?
THIS IS THE MOST IMPORTANT CONTROL POINT
Regulated negatively (inhibit conversion of Fructose 6 phosphate into Fructose 1,6 bisphosphate) by:
- ATP
- Citrate
- H+
These are the end products of glycolysis and the product of respiration, if these are in abundance, there’s no need for glycolysis to be continued, and therefore no need to keep producing Fructose 1,6 bisphosphate
Regulated positively by:
- AMP - this signals the energetic state of the cell
What inhibits phospho-fructokinase and what does inhibition of it lead to?
- High concentrations of ATP (lowers affinity for Fructose 6 phosphate for enzyme)
- Low pH
Inhibition of Phospho-fructokinase leads to inhibition of hexokinase, due to causing increase in G-6-P
How is pyruvate kinase regulated?
Regulated negatively by ATP
When is AMP produced?
When there are significant amounts of ADP due to high consumption of ATP, synthesis of ATP required
Enzyme Adenylate kinase converts 2 ADP molecules into ATP + AMP
What point can galactose enter the glycolytic pathway?
When it’s converted into glucose, it enters at the same point glucose begins at, which would be the very beginning of glycolysis
What point can fructose enter the glycolytic pathway?
- Fructose in adipose tissue can be phosphorylated into Fructose 6 phosphate, and will then enter the glycolytic pathway at that point, which would be the point at which Fructose 6 phosphate is phosphorylated into Fructose 1,6 bisphosphate
- Fructose in liver can be converted into DHAP or GAP, and will then enter at these points in the glycolytic pathway
What does pyruvate synthesise in anaerobic conditions?
What does this require?
Lactate, in exercising skeletal muscles
- This increases acidity, therefore reducing pH, and therefore would inhibit the actions of phospho-fructokinase, so the lactate would be removed and transported to the liver for metabolisation
This requires the oxidation of NADH into NAD+, therefore generating NAD
NAD+ is required to produce ATP, and therefore, NAD+ being produced by the formation of lactate allows the glycolysis pathway to continue (until pH becomes too low), so ATP can keeps being produced
Why do tumours use anaerobic glycolysis?
- As tumour size increases, need for blood supply increases, so tumour produces angiogenic factors, stimulating endothelial cells of nearby vessel to proliferate + migrate, leading to formation of vascular network
- Rate of tumour growth often too quick for scale of blood supply, so grow via anaerobic pathway
