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14 Cards in this Set

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  • Back
Where is the best step to regulate a synthetic pathway?

Where would a good inhibitor be placed in a pathway?
First step (most energy)

Final product (negative feedback, have enough of product so stop production)
4 Regulatory Strategies
1. allosteric control (reversible) = cooperativity feedback inhibition
2. multiple forms = metabolism in tissues
3. reversible covalent modification = phosphorylation
4. proteolytic activation (irreversible) = caspases blood clotting
Allosteric Regulation
-"other shap" regulation
-
What central metabolic cofactor provides energy for:
-muscle contraction
-maintainence of ionic gradients in NS biosynthesis
ATP: currency of life
adenosine triphosphate
-1 molecule traps 4 negative molecules in it (triphosphate, ribose sugar, adenine base)
-hydrolyze to break it = release energy
Why does hydrolysis of ATP have large -ΔG?
inorganic Phosphate can resonate (orthophosphate is low in energy)
-ATP is high energy bc it constrains 4 negative charges in small region
-hydrolysis frees the negative charge to separate physically in space & go down in energy
Glycolysis
-what is needed?

Gluconeogenesis
-what is needed?
Sugar-breakdown
-oxidizes glucose to pyruvate to produce ATP
-Need: 2ADP, 2NAD+
-Produces: 2ATP, 2NADH

Sugar-building
-hydrolyzes ATP to make glucose
-Uses: 4 ADP, 2 GTP, 2 NAD+
-Produces: 4 ATP, 2 GTP, 2 NADH
Why do regulated steps have large negative free energy?
-large free energy = irreversible (not in equilibrium)
-Step 1 (glucose --> G-6-P)
-Step 3 (fructose-6-P --> fructose-6-bisP) phosphofructokinase
-Step 10 (phosphenolpyruvate -->pyruvate)
What is the key regulator of glycolysis?
phosphofructokinase (PFK-1)
Glycolysis enzyme phosphofructokinase.
1. what are activators?
2. what are inhibitors?
1. F-2,6-BP, AMP

2. ATP, Citrate, H+, Lactate
Gluconeogenesis enzyme fructose1,6-BP.
1. what are activators?
2. what are inhibitors?
1. citrate

2. F-2,6-BP, AMP
Rate of catalysis change of phosphofructokinase with increasing [Fructose 6-P]
-hyperbolic curve
At high [ATP] how does phosphofructokinase 2/ increasing [Fructose 6-P] react?
sigmoidal (s-shaped) curve
-lowers PFK's affinity for Fructose 6-P
Describe Phosphofructokinase as a homotetramer that is allosterically regulated.
R-State:
-bind of F1-6BP to active site favors R-state (relaxed)

T-state:
-subunit w/out bound F1-6BP favors T-state (tight conformation)
Activation of phosphofructokinase by fructose 2,6-BP
-the sigmoidal velocity becomes hyperbolic in presence of fructose 2,6-BP
-ATP initially stimulates rxn
-as [ATP] increases it acts as an allosteric inhibitor
-inhibitory effect is reversed by frustose 2,6-BP