Module 7 - Metabolism Flashcards
How is energy produced
From metabolish of carbohydrate susch as sugar in our diet or glycogen storage in muscles or liver
Define Glycolysis
- highly regulated pathways that control the breakdown of carbs according to need
Gluconeogenesis
process to synthesise glucose de novo, glucose preferred by brain
What is the Pentose Phosphate pathway
an alternate pathway by which glucose is broken down to generate NADPH (for reductive biosynthetic processes such as fat synthesis) as well as providing ribose-5-phosphate (for nucleotide synthesis)
What is the structure of Glycogen
Highly branched
Alpha 1-4 bonds link to form subunits linear
Alpha 1-6 are branching points
single reducing end and several non-reducing ends
What is the fxn of non reducing ends
●Glucose resides are sequentially removed from several non-reducing ends during glycogen degradation, providing a rapid surge of glucose release when it is needed by the body.
what does Glygogen phosphoylase do
Glycogen Breakdown by catalyzing the phosphorylation of glycogen with the addition of PI (inorganic phosphate) which releases a glucose residue in the form glucose-1-phosphate
What does Glycogen synthase do
What energy source
- converts glucose-1-phosphate → Glycogen using Glycogen synthase
○ Catalyzes the synthesis of glycogen from glucose-1-phosphate using UTP as energy to drive this reaction forward
What does Phosphoglucomutase enzyme do.. using…
- converts glucose-1-phosphate → glucose-6-phosphate
How is Glycogen phosphorylase and glycogen synthase regulated
these enzymes are controlled by allosteric regulation and covalent regulation by phosphorylation
Describe the Allosteric Regulation of Glycogen Synthase
Glycogen synthase is activated by high concentrations of glucose-6-phosphate → signals there are plenty of carbs available for storage as glycogen
Describe the Allosteric Regulation of Glycogen Phosphorylase
- is activated by high concentrations of AMP, - indicates that the energy status of the cell is low (low ATP) signals an increase in glycogen phosphorylase to recluse more glucose residues for glycolysis to produce ATP
- is inhibited by high concentrations of ATP → - signals to the cell that there is an energy supply to meet the demand, and no further substrate needs to be broken down and utilized.
What does phosphorylation do
Covalent addition of a phosphate group to an enzyme can act as switch that turns the enzyme on and off depending on the enzyme in question
Covalent Regulation of Glycogen phosphorylase
- phosphorylation by an enzyme called kinase converts it to its active form
○Removal of the phosphate group by an enzyme called a phosphatase converts it back to its inactive form
Covalent Regulation of Glycogen synthase
Phosphorylation of glycogen synthase converts to its inactive form while removal of the phosphate group converts back to active form
Covalent Regulation of Glycogen synthase
Phosphorylation of glycogen synthase converts to its inactive form while removal of the phosphate group converts back to an active form
What signals regulate phosphorylation and dephosphorylation
●Hormonal signals regulate the phosphorylation and dephosphorylation by the kinase and phosphatase
○Insulin stimulates dephosphorylation by phosphate
○Glycogen and epinephrine stimulate phosphorylation by kinase
Glycogen Metabolism regarding Insulin
- Insulin elevates blood sugar which signals the glucose to be taken up to tissue for energy or be stored away
- Insulin binds to the receptor at the cell surface, signals for activation of glycogen synthase and inactivation of glycogen phosphorylase
Glycogen Metabolism regarding Glucagon
● Glucagon is counter regulatory to insulin
glycogen is released when glucose levels in the bloodstream drop and signals more glucose to be released from liver glycogen = glucagon inactivates glycogen synthase and activates glycogen phosphorylase
What can pyruvate and NADH do
Can be used to produce more ATP
How many reactions does Glycolysis have, what does it do, where does it take place
10 Reactions
converts sugar into pyruvate (3 C molecule)
Takes place in the cytosol
What happens during Step 1-5 of Glycolysis
- Converts a 6C sugar glucose into 2 3C sugars called glyceraldehyde-3-phosphate by consuming 2 ATP
- These reactions are catalyzed by kinase and are irreversible
- Called preperatory phase
What happens during Step 6-10 of Glycolysis
- one ATP is made per glyceraldehyde-3-phosphate in both reaction 7 and 10 (so 4 ATPS are produced by glycolysis)
- carried out by kinase reaction
Step 6: forms NADH called dehydrogenase which is an electron carrier with the potential to produce more ATPS through oxidative phosphorylation
Step 7: Reversible + ATP
Step 8: Irrreversible
STEP 10: ATP - 2 NADH, 4ATP are made
How is energy concerved in pay off phoase
By formation of 2 molecules of e- carrier NADH per molecule of glucose
What is the total and net rxn of glycolysis
Total: 4 ATP, 2 NADH, 2 Pyruvate
Net: 2 ATP, 2 NADH, 2 Pyruvate
What happens to Pyruvate and NADH
- pyruvate which oxidized in the mitochondria
- NADH can be oxidized by the electron transport chain of mitochondria
What are good points of regulation for Flux in Glycolysis
●Enzymes that catalyze reactions 1 and 3 are targets for the control of flux through glycolysis as these reactions have the largest change in free energy and are irreversible
How is Flux controlled in glycolysis through Step 1?
Step 1 is catalyzed by hexokinase, inhibited by its product, glucose-6-phosphate, via end-product inhibition
○ High concentrations of glucose-6-phosphate signal there is enough substrate for glycolysis to proceed and addition glucose does not need to be broken down
What is end product inhibition
the process whereby the end products of a pathway feedback and inhibit flux through an enzyme
How is Flux controlled in glycolysis through Step 3?
- Step 3: catalyzed by phosphofructokinase, inhibited by high concentrations of ATP and citrate
- ATP signals enough levels of ATP and flux through glycolysis can be down regulated
- Citrate (first product in the tricarboxylic acid cycle) signals not enough substrate for the tricarboxylic acid cycle and further glucose does not need to be broken down
- phosphofructokinase UPREGULATED by high concentrations of AMP and ADP which signal low energy status
- allosterically upregulated by Fructose-2,6-bisphosphate
What must be regenerated for glycolysis to occur
NAD+ must be regenerated from NADH
O2 is present its done in the transport chain in mitocondria
What happesns to NAHD when there is no O2
wats the net oxidation?
NADH is not converted back to NAD+ in mitochondria
- Fermentation occurs when O2 is absent and can regenerate NAD+
- It produced ATP w/ no net oxidation of C
What are the two strategies regarding fermentation
Strategy 1: Formation of Lactate
Strategy 2: Formation of Ethanol
Describe Strategy 1 of Fermentation
Strategy 1: Formation of Lactate
●Enzyme lactate dehydrogenase oxidizes
NADH pyruvate becomes lactate which allows dor regenerating NAD+ which will continue to allow for glycolysis
●Intense exercise forms lactate which can contribute to soreness and fatigue
- 2Lactate + 2ATP
Describe Strategy 2 of Fermentation
Strategy 2: Formation of Ethanol
●Occurs in yeast and other microorganisms
●In yeast, ethanol (from pyruvate) is produced rather than lactate during fermentation which regenerates NAD+ and allows glycolysis to continue
- CO2 is also produced
- 2 ethanol + 2CO2 + 2ATP
What is the net reaction of fermentation
●Under conditions where O2 is absent, fermentation can still produce 2 molecules of ATP to meet the cell’s demands for ATP
What is gluconeogenesis an what are some precursors
● Gluconeogenesis is de novo synthesis of glucose
● Supplies glucose to the body when glycogen stores are low
● Precursors like some amino acids, citric acid cycle intermediates and lactate-via-pyruvate is converted to oxaloacetate which is converted to glucose through gluconeogenesis
Is gluconeogeneis the reverse of glycolysis and is energy required
No, not exactly the reverse’
Yes input is required
Is gluconeogenesis Energetically Favourable
● The 3 non-equilibrium reactions in glycolysis with large changes in free energy are by-passed in gluconeogenesis
● The near-equilibrium reactions are shared btwn the two pathways
● Concentrations of substrates are different under the metabolic circumstances that occur when gluconeogenesis is required thus driving near-equilibrium rxns in reverse direction
● Non-equilibrium reactions proceed differently in reverse direction
Net reaction of Gluconeogenesis
4 ATP + 2 Pyruvate + 2GTP + 2 NADH
Glycolysis vs Gluconeogenesis
- not exactly reverse
- Step 1,3 and 10 (Enzymes: glucokinase, phosphofructokinase and pyruvate kinase) need to be bypassed
- The rxns are by-passed by glucose-6-phosphatase, fructose bisphosphatase, PEP carboxykinase and pyruvate carboxylase
How is Flucx controlled through Gluconeogenesis
- Flux regulated reciprocally to flux through glycolysis to avoid futile cycling
- Key point in regulation occurs at fructose bisphosphatase
● the fructose bisphosphatase is inhibited by high concentrations of AMP and fructose-2,6-bisphosphatase - This is in contrast to phosphofructokinase (which catalyzes opposite rxn)
How are F6P (fructose-6-phosphate) and F1,6P (fructose-1,2-bisphosphate) regulated
Fructose-6-Phosphate
-High concentration of AMP and F2,6P inhibits fructose bisphosphatase from making Fructose-6-Phosphate in gluconeogenesis
Fructose-1,6-bisphosphate
- High ATP and Citrate inhibit phosphofructokinase needed to make F1,6P
- High AMP & ADP activate phosphofructokinase needed to F1,6P
What is the pentose phosphate pathway
is an alternate pathway where glucose is broken down to generate NADPH for reductive biosynthetic processes like fat synthesis or providing ribose-5-phosphate for the biosynthesis of nucleotides depending on cell needs
● The oxidative phase where glucose-6-phosphate is oxidized generates NADPH and waste product CO2
How does PPP makes ribose 5 phosphate
● Under conditions where ribose-5-phosphate is required for nucleotide synthesis, pentose phosphate pathway diverts carbons to its production
One pathway of PP makes ribose-5-phosphate what is the alternative?
- the C’s are further metabolized to two fructose-6-phosphate and one glyceraldehyde-3-phosphate from 3 original glucose-6-phosphate molecules
- also made 3CO2 + 6NADPH
●These intermediates then feed into glycolysis and are further metabolized for energy generation
What is the total cost of making glucose De Novo (gluconeogenesis)
at the cost of 6 ATP equivalents per glucose
- not reverse of glycolysis
4 ATP 2 GTP
What is Fermentation
○Glycolysis can proceed in the absence of oxygen under anaerobic conditions called fermentation in which lactate production and in yeast ethanol is generated as a byproduct
How are the high energy steps (1,3,10) in glycolysis overcome in gluconeogenesis
- The rxns are by-passed by glucose-6-phosphatase, fructose bisphosphatase, PEP carboxykinase and pyruvate carboxylase
