How chemotherapy actually works: antimetabolites

In the cell there are countless numbers of reactions taking place every second. The word metabolism refers to all these essential chemical reactions. A metabolite is a term for the organic (carbon and hydrogen containing) compounds which are constantly being made, regenereated, broken down in our cells. For example, amino acids, the monomer of proteins, is a metabolite.

Antimetabolites are compounds which have an almost identical structure to the metabolites, ie they mimic the structure, but do not perform the same function – due to slight structural differences, the body cannot use them. Thus, by flooding the body with these antimetabolites, vital metabolic reactions cease to function as they become use the antimetabolites instead of the correct compounds, in effect jamming the cellular machinery.

In cancer, antimetabolites jam the replication machinery. The specific metabolic pathways are those involved with the production of nucleic acids RNA and DNA – the blue-prints of proteins and life

Making Thymine from Uracil

One antimetabolite used in chemotherapy inhibits an essential enzyme. Normally, in the process of protein synthesis, the pyrimidine uracil must be converted to thymine – two building blocks which form part of RNA and DNA respectively, called ‘nucleotides’,

The enzyme Thymidylate Synthase usually adds a CH3 group (methyl) to the 5th Carbon on Uracil.

One chemotherapeutic agent is called ‘5-FU’. This mimics the uracil, but has a fluorine atom on the 5th carbon, where the CH3 group would go. Thus, no thymine can be made, so DNA can’t be produced. The name of the drug implies its function – attaches an F to the 5th carbon on Uracil.

Antifolates

Antifolates are ‘folate antagonists’. These are inhibitors of an enzyme dihydrofolate reductase (DHFR). This enzyme is involved with synthesis of nucleotides. If the enzyme is blocked, no nucleotides can be produced, so cell division halts. One example of an antifolate is methotrexate.

Folic acid is a key growth factor which plays a chief role in nucleotide synthesis – it is a co-enzyme (a non-protein compound necessary for the functioning of an enzyme) which brings CH3 groups to be attached to various compounds.

Folic acid is inactive until it is chemically reduced – ie hydrogens are added to it. DHFR is an enzyme which activates the folic acid by reducing it, making dihydrofolate and then tetrahydrofolate. Methotrexate is a competitive inhibitor of the enzyme DHFR, ie it binds reversibly but tightly to its active site. Thus, less DHFR can work, so the cell cannot produce new nucleotides, which are needed to make DNA. Consequently, the cell cannot replicate, since it would need to copy and double its DNA.

http://www.cancerquest.org/chemotherapy-antimetabolites.html

Advertisements

2 thoughts on “How chemotherapy actually works: antimetabolites

  1. Hi, thanks for the interesting and highly informative article. I wonder how many of these anti-tumor strategies may be applicable to fighting infection as well – i.e. exploiting the different metabolism of microorganisms to selectively eliminate infectious agents. Also, it would be cool if we could target specific metabolites present in tumor/metastasizing cells that are not common to all growing/dividing cells, thus removing some of the side effects of these drugs.

    Liked by 1 person

    • One thing which I was wondering about but has actually been done is using chemotherapy to treat immune conditions like HIV – obviously the virus resides in T helper cells, so obliterating a suffer’s immune system with chemotherapy and then reintroducing it seems logical. However people many not want to go through the stress of chemo – its is quite a debilitating treatment. Have you read about the girl Layla who was treated basically using what you suggested?? I think you’ll find it quite exciting!

      Liked by 1 person

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s