Enzymes and Metabolism Flashcards
what are cofactors called when they are loosely or tightly bound
tightly bound- prosthetic
loosely bound to enzyme- coenzyme
what rxn does hexokinase catalyze and how is its function measured
To monitor the reaction catalyzed by hexokinase, the appearance of the product, glucose-6-phosphate, is measured.
The second substrate, ATP, is either added in excess, or is continually regenerated during the reaction (both these conditions pertain in cells) so that it can be ignored as a variable.
How to enzymes impact equillibrium
they speed up the fwd as well as the reverse rxn to speed up the approach to equilibrium
how is the amount of enzyme reported
in U, units of enzyme activity
1 U is the amount of enzyme that will transform 1 μmole of substrate per minute under defined conditions (temp, pH, ionic strength, etc.)
This may, for example, be expressed as U/dLor U/mg of total protein.
In brain and muscle, glucose utilization remains high during fasting. YET, In liver and pancreatic βcells, glucose utilization increases as blood glucose increases. How can glucose have differential effects ?
Tissue-Specific Isozymes of Hexokinase differ in KM for Glucose
Hexokinases for brain and muscle remain maximally active even at the lowest physiologic concentrations of glucose
The liver and pancreas is sensitive to the concentration of blood glucose. It is therefore able to act as a glucose sensor in pancreatic βcells, and as a pacemaker for glycogen synthesis in liver.
- Km is the substrate concentration which is required for 1/2 Vmax*
- The physiological range of glucose concentrations in the blood is approximately 4-15 mM*
ID what kind of glucose metabolism is demonstrated by each curved line
A- brain
B- muscle
C- liver and pancreas
the shaded line is the normal physiological range
4-15 mM
explain inborn error of metabolism
Heterozygous errors are functionally normal and show a mendelian recessive pattern of inheritance.
Homozygous errors cause an increase upstream and a decrease downstream. Flux is severly reduced. If the metabolites are toxic, cellular damage ensues.
At steady state, the flux through all steps in a pathway is, by definition, the same, explain how this impact the rate limiting step
THERE IS NO SINGLE RATE LIMITING STEP
the flux through a pathway can be changed by altering the activity of any of its constituent enzymes (provided the change is of sufficient magnitude) - no ONE enzyme is dominant in this respect
Give an example of the regulation of a pathway by availability of its substrate (feed forward), and of a feed back mechanism for PFK
A rise in [AMP] indicates the need to increase ATP production by activating PFK and hence increasing glycolytic flux. Through allostericactivation of PFK-1
Glycolysis is regulated by citrate via allosteric inhibition of PFK-1.
What are the three ways to impact an enzymatic pathway
feedforward, feedback, increasing the enzyme concentration of ALL enzymes in the pathway( by transciprional control)
Compare and contrast the Warburg Effect vs the Pasteur Effect
Pasteur Effect: Adaptation to Changing O2Availability
With abundant O2, pyruvate may be metabolized via the TCA cycle and oxidative phosphorylation with reduced glycolytic flux
With limited O2, pyruvate is instead converted to lactate, and glycolytic flux must be increased.
Warburg Effect: Meeting the Demands of Cell Proliferation
In cancer cells, even with abundant O2, pyruvate may be converted to lactate. Glycolytic flux may be as much as 200 x higher than in corresponding normal cells.
Name the molecular components of enzymes and describe how these components contribute to enhancement of reaction rates.
coenzymes, prostethic groups, and metal ions
metal ions- Mg2+, Ca2+, Zn2+, Mn2+, etc. act as electrophiles; assist in binding of substrate; stabilize reaction intermediates; accept or donate electrons in redox reactions; and act as structural components of enzymes.
What would occur if all the enzymes in the pathway were changed coordinately
The levels of the intermediary metabolites will not change, but the flux through the pathway will change in proportion to the change in enzyme quantities
