Regulation of Metabolism Flashcards
Why does metabolism require control?
- To co-ordinate metabolic processes
- Vital that some of the enzymes involved in these processes are subject to strict controls
What are 4 factors that may be involved in the regulation of biochemical pathways?
- Concentrations of substrates and products
- Modifications
- Endocrine signals
- Other enzymes
General Mechanisms of Enzyme Regulation: What did Leonor Michaelis and Maud Menten propose?
- That the enzyme reversibly combines with its substrate
- To form an ES complex that subsequently breaks down to product, regenerating free enzyme
What does the Michaelis-Menten equation describe?
Describes how reaction velocity varies with substrate concentration
What is the Michaelis-Menten equation for the formation of an ES complex?
What is the Michaelis-Menten equation for how velocity varies with substrate concentration?
What are the assumptions of the Michaelis-Menten Equation (3 points)
- [S] is small, much greater than [E], so that the amount of substrate bound by the enzyme at any one time is small.
- [ES] does not change with time as it is in ‘steady state’
- Only initial velocities are used in analysis of enzyme reactions, as it is only at this time when the reaction is linear with time
What is The Michaelis constant
Km
What is Km characteristic of and what does it reflect?
- characteristic of an enzyme and its substrate
- reflects the affinity of the enzyme for that substrate
What is Km numerically equal to?
Numerically equal to [S] at which the reaction velocity is at ½Vmax
Km does NOT vary with with what?
Km does not vary with the concentration of enzyme
What does a numerically small Km (low) reflect?
- reflects a high affinity of the enzyme for substrate
-because a low concentration of substrate is needed to half-saturate the enzyme - i.e. to reach ½Vmax.
- Enzymes like this are usually targeted for regulation
What does a numerically large Km (high) reflect?
- reflects a low affinity for the substrate
- because a high concentration is required to half-saturate the enzyme
- Enzymes like this are not usually targeted for regulation
What is the rate of reaction for the Michaelis-Menten Equation directly proportional to?
The enzyme concentration [S]
What is the order of reaction for enzyme regulation?
When [S] is much less than Km:
-The velocity of the reaction is roughly proportional to [S]
-The rate is said to be first order with respect to substrate
When [S] is much greater than Km:
- The velocity is constant and equal to Vmax
- The rate of reaction is then independent of [S]
- Is said to be zero order with respect to substrate concentration.
Allosteric Modification
Some molecules may bind non-covalently to an enzyme…. What does this result in and what are these molecules called?
- Inhibits the activity of said enzyme
- Molecules that do this are called effectors
What are the two types of effectors?
- Homotropic Effectors
- Heterotropic Effectors
What are the main characteristics of Homotropic Effectors?
- When the substrate is an effector
- They are usually positive
- Significance: Km is decreased several fold for a small increase in [S].
What are the main characteristics of Heterotropic Effectors?
- The effector is not the substrate
- May have a stimulatory or inhibitory effect
What is a very rapid (instantaneous) form of regulation?
Allosteric modification
What does induction and Repression of Synthesis represent?
- Represents adaptive regulation - whereby enzyme synthesis is either enhanced or decreased by certain physiological situations
- Slow (days) mechanism of regulation
How are the processes of glycogen synthesis and glycogen breakdown reciprocally regulated
- allosterically
- covalently
- induction/repression of synthesis
What are the key regulatory enzymes in glycogen metabolism?
SYNTHESIS: Glycogen Synthase
BREAKDOWN: Glycogen Phosphorylase
Fed state of glycogen metabolism:
Glucose converts to? ——->
Glucose—–>Glycogen
Fasted state of glycogen metabolism:
Glycogen converts to? ——->
Glycogen—–>Glucose
What does glucose 6-phosphate activate and inhibit in glycogen metabolism (allosteric regulation)
Glucose 6-phosphate….
Activates:Glycogen Synthase
Inhibits:Glycogen phosphorylase
Allosteric regulation:
What is AMP and how is it generated?
- AMP= Adenosine Monophosphate
- AMP is generated when skeletal muscle uses ATP to contract
AMP has no effect on glycogen synthase but does what instead?
Allosterically activates Glycogen phosphorylase – very important in exercising skeletal muscle
Allosteric regulation:
What does a high concentration of ATP mean?
- Means the energy status of the cell is very high
- Hence there is no requirement to breakdown Glycogen
ATP has no effect on glycogen synthase but does what?
- ATP allosterically inhibits Glycogen phosphorylase
In a fed state, there is an increase of glucose concentration.
So there is no need for what?
- no need to continue breaking down glycogen for glucose production
What does glucose allosterically inhibit?
- Allosterically inhibits glycogen phosphorylase
- with no effect on Glycogen Synthase
-very important for the liver
Allosteric regulation of enzymes is classified as what type of regulation?
‘Within the cell’ regulation
Allosteric regulation involves the binding of what? and what does this result in?
- Involves the binding of an effector molecule to the enzyme
-Thereby altering its activity
Covalent regulation of metabolic processes is usually in response to what? and give an example.
An extracellular stimulus
- Such as from a hormone which then binds to an extracellular receptor
- leads to a cascade of biochemical events leading to an effect on the target enzymes