Highlights Controlling Enzymes II

1. Last time I discussed how enzymes could be controlled by controlling whether or not the mRNA needed to make them was synthesized. That method is very effective, but rather slow in response time.

2. Another way of controlling the activity of enzymes is MUCH faster. It involves ALLOSTERY. Allostery is a method whereby a small molecule binding to an enzyme has an effect on an enzyme's activity. That effect can be negative (stops or slows enzyme activity) or positive (starts or increases enzyme activity).

3. An example of a situation in which allostery is used is feedback inhibition.

4. Feedback inhibition is a very effective way of controlling an entire metabolic pathway. Metabolic pathways are like roadmaps, with molecules representing the towns. A metabolic pathway might have the following reactions

A->B->C->D

Reaction A->B might be catalyzed by enzyme 1, B-> C catalyzed by enzyme 2, and C->D catalyzed by enzyme 3

Feedback inhibition in this system would work as follows. Accumulation of molecule D would inhibit enzyme 1. With enzyme 1 inhibited, B would not be made, so C would not be made, so more D would not be made. Thus, with feedback inhibition one molecule could effectively stop an entire pathway by inhibiting one enzyme.

5. Not all allostery is negative in nature. Some enzymes are activated by binding to small molecules. For example, one of the enzymes that catalyzes the breakdown of glucose is stimulated when it binds to AMP. AMP is a molecule that appears when cells are low on energy. Thus, when cells need energy, they activate the pathway of breaking down glucose by activating a critical enzyme.

6. When one uses cells to make products in biotechnology, one frequently uses cells that have alterations to the things that control their pathways. For example, penicillin can be isolated in quantities a hundred times greater from some molds that have mutated to lose control over how much they make. These mutations can occur naturally in nature or be engineering by scientists in laboratories.

Highlights Viruses I

1. Viruses come in many forms. All of them have coats made of protein that protein the nucleic acid inside. The nucleic acid contains the important genetic information necessary for reproducing the virus. The nucleic acid for some viruses is DNA and for other viruses it is RNA.

2. Some RNA viruses include measles, rabies, HIV, influenza, and polio.

3. All viiruses have a life cycle. In general terms, it includes the following things a) attachment to a host cell; b) injection of viral nucleic acid; c) synthesis of viral proteins and copying of viral nucleic acid by the cell using information in the viral nucleic acid; d) packaging the replicated viral nucleic acids; and e) exit from the cell (usually by bursting the cell).

4. Viruses can have a phase of their life cycle that is "lytic", as in point #3 or they can be rather dormant. The dormant phase is known as being non-lytic. In this phase, the virus doesn't replicate and kill the cell until the time is opportune.

5. HIV is an example of an RNA virus. It is called a retrovirus because during its life cycle, it converts from RNA to DNA.

6. HIV's life cycle goes as follows: a) attachment to a protein called CD4 on the surface of immune system cells; b) injection of the HIV RNA into the cell; c) conversion of the HIV RNA to DNA by an HIV enzyme called reverse transcriptase; d) integration of the HIV DNA into the host chromosome. The HIV DNA can remain dormant and the cell with the HIV DNA now can replicate. Each replication includes the HIV DNA, so millions of immune system cells can be made, each with HIV DNA.

7. After a while, the RNA polymerase of the host cell will copy the HIV DNA to make many copies of HIV RNA. This HIV RNA can be translated and HIV proteins are made. The HIV proteins include proteins making up the coat of the virus. A necessary step in getting the viral coat proteins ready is that they must be cleaved by a protease. If the protease doesn't work, the virus can't be assembled.

8. Thus, strategies for stopping HIV include drugs that inhibit the reverse transcriptase, the integrase, and the protease.

9. Though drugs are very good at reducing the replication of the virus and the packaging of the virus, one can't cure a person of HIV with drugs without killing all of the cells that contain integrated HIV in their chromosomes.

10. Another problem with the HIV virus is that it mutates VERY rapidly. The more rapidly it mutates, the more chances it creates for finding a way of avoiding the limitations created by the drugs.