Cell cycle and enzymes kinetics

Question 1

What is the main goal of the somatic cell cycle?

Answer 1

To ensure exact duplication of the genome in the S phase, and exact division of the genome in the M phase to create two identical daughter cells.

Question 2

How do cells regulate their size by coordinating growth with division at the restriction point R” in G1?”

Answer 2

At the R point, the cell determines whether or not it is big enough to move on to S phase.

Question 3

How do cells prevent re-replication of their genome?

Answer 3

By keeping the assembly and activation complexes in separate cell cycle phases.

Question 4

What can result from chromosome re-replication in S phase, or mis-segregation - forms of genomic instability?

Answer 4

Diseases like cancer and birth defects (trisomy 21).

Question 5

What does it mean that differentiated, post-mitotic cells (like neurons) are stuck at the R” point?”

Answer 5

They will continue to grow without cycling.

Question 6

What do cell cycle checkpoints do?Where are some of the checkpoints?

Answer 6

They are surveillance units that ensure genomic stability.G1 phase: R site makes sure the cell is large enough to enter the cell cycleS phase: if DNA is damaged, it will not proceed to mitosisM phase: if mitotic spindles are damaged, cell will exit mitosis

Question 7

What is the mechanism of cell cycle checkpoints?

Answer 7

A sensor (Rad 17) will sense DNA damage. The sensor will signal a transducer (ATM) to phosphorylate (activate) an effector protein (p53, CHK2). The effector will stop the cell cycle either on its own or, in the case of p53, by inhibiting CDK.

Question 8

What are some cell cycle regulators that are altered in cancer cells that are being used in patient diagnosis and prognosis?

Answer 8

CDK’s: help with cell proliferation, are elevated in some cancersBRCA 1,2: Mutations indicate a DNA checkpoint defect leading to higher risk of genomic instability and breast cancer

Question 9

What are the main differences between mitosis and meiosis?

Answer 9

Meiosis produces haploid gametes. The cells undergo two divisions after DNA replication.

Question 10

What is an enzyme?

Answer 10

A biological catalyst. A compound that increases the rate of a chemical reaction without being changed in the process. Enzymes form a specific three dimensional structure with the active site.

Question 11

What is activation energy?How does it relate to enzymes?

Answer 11

The energy it takes to start a reaction.Enzymes decrease the activation energy of a reaction by positioning the reactants in a favorable way, thus speeding the reaction.

Question 12

What is the free energy of a chemical equation?How is this related to enzymes?

Answer 12

The energy in a chemical system that can be converted to do work.Enzymes can help reactions that are energetically favorable (negative delta G) but slow (high activation energy) occur at a rate that is physiologically favorable by stabilizing the transition state (reducing activation energy).

Question 13

What is a cofactor?

Answer 13

A substance (often a metal) that needs to be present in addition to an enzyme to catalyze a reaction. The cofactor does not donate a chemical group to the reaction.

Question 14

What is a coenzyme?

Answer 14

A small molecule that works with the enzyme that donates a chemical group that will be used in the reaction.

Question 15

How do enzymes lower the energy of the transition state when binding the substrate?

Answer 15

Multiple, weak, non-covalent interactions bind the substrate in such a way that it would be oriented in the high energy transition state, which provides both specificity and catalysis.

Question 16

How do enzymes alter the transition state through binding using the induced fit model?

Answer 16

The enzyme has to favor the transition state because this is how the reaction would be sped up. When the substrate binds, the two form a complex that lowers the activation energy of the reaction. Binding of the substrate at its transition state is stabilized by the weak non-covalent bonds.

Question 17

How do enzymes work by using covalent chemistry?

Answer 17

A transient covalent bond can form between the enzyme and the substrate.

Question 18

How do enzymes work by using metallic ion chemistry?

Answer 18

Bound metal ions can help position the substrate or can be a driving force in redox reactions. This is used by about 1/3 of enzymes.

Question 19

How do enzymes work using acid base chemistry?

Answer 19

Amino acid side chains can donate or accept protons to stabilize transition states.

Question 20

What is Km?

Answer 20

The substrate concentration at which the enzyme velocity will be at 1/2 Vmax.

Question 21

What is Kcat?

Answer 21

Kcat is called the turnover number. It is equivalent to the number of substrate molecules converted to product in a given unit of time on a single enzyme molecule when the enzyme is saturated with substrate.

Question 22

How do competitive inhibitors work?What is the effect on Km? Vmax?

Answer 22

A competitive inhibitor binds only the enzyme so that the normal substrate cannot bind, and thus competes with it.Km increases, Vmax is unchanged

Question 23

How do uncompetitive inhibitors work?What is the effect on Km? Vmax?

Answer 23

Inhibitor binds to substrate-enzyme complex and blocks the catalytic step.Apparent Km increases, Lowers Vmax

Question 24

How do mixed inhibitors work?

Answer 24

The inhibitor binds outside of the active site and can bind either to E or ES. Both Km and Vmax are effected.

Question 25

What are the reversible inhibitors?

Answer 25

CompetitiveUncompetitiveMixed

Question 26

How do irreversible inhibitors work?

Answer 26

They combine with or destroy a functional group on an enzyme that is essential for the enzyme’s activity. They make the enzyme non-functional, irreversibly.

Question 27

What is a noncompetitive inhibitor?

Answer 27

A type of mixed inhibitor that can bind E and ES but do not affect substrate binding, although they still do reduce activity.

Question 28

How does allosteric regulation of enzymes work?

Answer 28

Often, binding of another molecule (a regulator) will bind to the enzyme and change the conformation and thus function of the enzyme. This occurs often in feedback loops, when a downstream product of a pathway regulates an enzyme early in the pathway.

Question 29

How does covalent modification of an enzyme help regulate it?

Answer 29

Phosphorylation or another post-translational modification can either activate or deactivate an enzyme. This occurs often in response to intra or extracellular signals and conditions.

Question 30

How can the binding of a regulatory protein regulate enzymes?

Answer 30

Much like allosteric regulation, small peptides can bind to enzymes to turn them on or off.

Question 31

How does proteolytic cleavage regulate enzymes.

Answer 31

Some enzymes are inactive when first made, but are cleaved (generally by another protein) into smaller fragments to become active. E.g. Chymotrypsinogen, cleaved by trypsin, to chymotrypsin.