Metabolism Flashcards
What are the three stages of metabolism?
Step 1 = breakdown of macromolecules
- Occurs outside of cells
- Macromolecules –> subunits
Step 2 = glycolysis & krebs’ cycle
- Occurs in the cytosol (final step in the mitochondria)
- Production of ATP + NADH
Step 3 = oxidative phosphorylation
- Occurs in the mitochondria
Define anabolic and catabolic metabolism
Anabolic - construct molecules from smaller units (i.e. use energy)
Catabolic - breakdown molecules from larger units to produce energy (often referred to as “useful” metabolism)
Define the following type of metabolic reaction:
- Oxidation-reduction
- Ligation (req. ATP cleavage)
- Isomerisation
- Group transfer
- Hydrolytic
- Addition/Removal of functional group
REDOX = electron transfer
Ligation = formation of covalent bond (eg: C-C)
Isomerisation = re-arrangement of atoms (i.e. forms isomers)
Group transfer = transfer of functional group from one molecule to another
Hydrolytic = cleavage of blond + addition of water
Addition/Removal of functional group = to double bond
Where does ATP carry its energy?
Energy is carried within the phophate bonds (anhydride bonds)
Define free energy
Free Energy (G) is defined as the amount of energy within a molecule that could perform useful work at a constant temperature (units = kJ/mole)
What is ∆G?
∆G is negative, leading to an increase in disorder of the system, release of heat.
What is the main way of generating ATP?
Glucose combustion
Give the formula/equation for glucose combunstion
C6H12O6 + 6O2 –> 6CO2 + 6H20
What is a coupled reaction? Why is it within the cell’s interest to have coupled reactions?
Many cellular reactions required energy (i.e. they are energetically unfavourable) therefore they are coupled with energetically favourable reactions (i.e. reactions that form energy). This ensures that overall, the cell is energetically neutral
What are the two main ways of making ATP (within the cell)?
- Substrate Level Phosphorylation - the direct transfer of one phosphate group from an intermediate substrate to ADP throughout a biochemical pathway (eg: glycolysis)
- Electron Transfer - energy derived from the ETC is used to produced ATP (eg: oxidative phosphorylation)
What is NAD? Describe its role
- NAD+ (Nicotinamide adenine dinucleotide) is a co-enzyme
- Critical co-factor for dehydrogenase reactions
- Catalyses the dehydrogenation of substrates
- Acceptor of one hydrogen atom and two electrons
- Note - it has no effect on its own but functions only after binding to a protein.
What is glycolysis?
Glycolysis is the anaerobic metabolic pathway that converts glucose into pyruvate
What is the net yeild of glycolysis?
Net Yeild = 2 x ATP, 2 x NADH
(Total = 4 x ATP, 2 x NADH)
What are the three general phases of glycolysis
- Energy Investment (steps 1 - 3)
- Glucose → Fructose 1,6-bisphosphate
- Energy Usage (steps 4 - 5)
- Fructose 1,6-bisphosphate → Glyceraldehyde-3-phosphate
- Enegy Release (steps 6 - 10)
- Glyceraldehyde-3-phosphate → Pyruvate
Outline the 10 steps of glycolysis
(i.e. give the 10 molecules involved)
- Glucose
- Glucose-6-Phosphate
- Fructose-6-Phosphate
- Fructose-1,6-Bisphosphate
- Glyceraldehyde-3-Phosphate
Dihydoxyacetone-Phosphate - Glyceraldehyde-3-Phosphate
- 1,3-Bisphosphoglycerate
- 3-Phosphoglycerate
- 2-Phosphoglycerate
- Phosphoinol-Pyruvate
- Pyruvate
How many reactions are involved in glycolysis?
10
Glycolysis: Reaction 1
Reaction 1: Phosphorylation
Reaction: Glucose –> Glucose-6-Phosphate
Enzyme: Hexokinase
Energy: 1 x ATP –> ADP (i.e. requires energy)
This is the first phosphorylation event and is irreversible
Glycolysis: Reaction 2
Reaction 2: Isomerisation
Reaction: Glucose-6-Phosphate à Fructose-6-Phosphate
Enzyme: Phosphoglucose Isomerase (shuffling of phosphate forming open chain form)
Product: Water
Glycolysis: Reaction 3
Reaction 3: Phosphorylation
Reaction: Fructose-6-Phosphate –> Fructose 1,6-bisphosphate
Enzyme: Phosphofructokinase
Energy: 1 x ATP –> ADP (i.e. energy usage)
Glycolysis: Reaction 4
Reaction 4: Cleavage
Reaction: Fructose 1,6-bisphosphate –> glyceraldehye-3-phophate + dihydroxacetone phophate
Enzyme: Aldolase (2x 2C molecules formed)
Glycolysis: Reaction 5
Reaction 5: Reduction/Fixation
Reaction: glyceraldehye-3-phophate fixation
Enzyme: **Triose phosphate isomerase **
Glycolysis: Reaction 6
NB: reaction 6 = 2 parts - hydrogenation + phosphorylation
Reaction 6: **Hydrogenation **
Reaction: 2 x glyceraldehye-3-phophate
Enzyme: **Triose phosphate dehydrogenase **
Product: 2 x NAD –> 2 x NADH (hydrogenation of NAD)
2 molecules created as the pathway splits in two at this point - i.e. from this point, everything happens twice
Reaction 6: **Phosphorylation **
Reaction: glyceraldehye-3-phophate –> 1,3-bisphophoglycerate
Enzyme: glyceraldehyde 3-phosphate dehydrogenase
Product: ADP –> ATP (i.e. energy generation) (2 in total - one produced in each branch)
Glycolysis: Reaction 7
Reaction 7: Phosphorylation (relocation of C bond)
Reaction: 1,3-bisphosphoglycerate –> 3-phosphoglycerate
Enzyme: Phosphorglycerate Kinase
Glycolysis: Reaction 8
Reaction 8: Dehydration
Reaction: 3-phosphoglycerate –> 2-phosphoglycerate
Enzyme: Phosphoglycerate Mutase
Glycolysis: Reaction 9
Reaction 9: Transfer
Reaction: 2-phosphoglycerate –> phosphoinol-pyruvate
Enzyme: Mutase
Glycolysis: Reaction 10
Reaction 10: Phosphorylation
Reaction: phosphoinol-pyruvate –> pyruvate
Enzyme: pyruvate kinase
Product: ADP –> ATP (one produced in each branch, 2 in total)
Pyruvate Kinase transfers high energy phosphate group to ADP forming ATP
phosphoinol pyruvate becomes pyruvate
How many possible fates does pyruvate have?
Three
(two anaerobic - alcoholic fermentation & generation of lactate, one aerobic - acetyl coA)
What is the general purpose of the anaerobic fates of pyruvate?
Generation of Lactate/Alcohol Fermentation enable the regeneration of NAD+ which allows glycolysis to continue, even in situations of oxygen deprivation
Discribe alcoholic fermentation of pyruvate
- one of two anaerobic fates of pyruvate
- product = ethanol
- biproduct = water + carbon dioxide
- co-factor = NADH –> NAD+ (purpose of the reaction)
- Not major reaction in humans
Describe the generation of lactate
- the major anaerobic fate of pyruvate
- reaction occurs in the liver
- pyruvate is fermented to lactate
- There is no oxidant therefore the cell recycles NADH converting pyruvate into lactate
- lactate can be converted back to glucose
- occurs during intense exercise (anaerobic metabolism - oxygen is limiting factor)
- generates free NAD+ which is needed by the muscle for other reactions.
- lactate diffuses from the muscle into the blood stream and is picked up by the liver, where the high levels of NAD+ can be used by lactate dehydrogenase to regenerate pyruvate.
How can LDH be used diagnostically?
LDH = lactate dehydrogenase
- Function = catalyses lactate –> pyruvate
- Distribution = various body tissues (heart, muscle, liver etc.)
- Elevated levels = indicator of several disorders therefore testing is a useful diagnostic tool
- Heart attack
- Stroke
- Liver disease
How can creatine kinase be used diagnostically?
A large reservoir of creatine phosphate is on hand to buffer demands for phosphate in the following reaction:
CP + CK –> Creatine + ATP
CK can be used diagnostically - because, when a muscle is damaged, creatine kinase leaks into the bloodstream. Elevated levels suggest:
- Heart attack
- Chest pain
- Duchenne’s
Describe the generation of acetyl coA
- The only aerobic fate of pyruvate
- Pyruvate enters the Krebs Cycle where it is oxidised (final product = acetyl coA which then enters TCA cycle)
- Occurs in the mitochondria
What is the committed step of the Krebs’ Cycle
The first step - the conversion of pyruvate to acetyl coA (by the pyruvate dehydrogenate complex)
What is the Pyruvate Dehydrogenase Complex?
- Not a single enzyme but a complex of three enzymes
- 5 co-factors involved
- Thiamine pyrophosphate (TPP)
- lipoamide
- FAD
- CoA
- NAD+