Saturday, January 11, 2014

Parkinson's disease and dopamines role

          Parkinson’s disease is a liberal neurological disorder which affects the motor system and thus individual’s ability to move. It is caused by the slow progressive degradation of neurons due to either genetic or environmental effects and the lack of dopamine in the substantia nigra of the brain. Dopamine is a neurotransmitter essential for the transfer of neuronal signals from the brain to the spinal cord and eventually to the appropriate muscles in the body. The shortage of dopamine in patients suffering Parkinson’s disease thus leads to the impairment of their muscular function. 

           Dopamine is produced from the conversion of L-tyrosine through the intermediate product dihydroxyphenylalanaine (L-DOPA) in step-wise process catalyzed by specific enzymes. This process occurs in the dopaminergic neurons of substantia nigra.
The following shows the complete 2-step reactions of dopamine production.
1)    Catalysed by tyrosine 3-monooxgenase
L-tyrosine + THFA  + O2 + Fe2+ L-dopa + DHFA + H2O + Fe2+
2)    Catalysed by dopa decarboxylase
L-dopa + pyridoxal phosphate dopamine + pyridoxal phosphate + CO2


           Any deficiencies of the substrates required for L-dopa formation such as L-tyrosine, iron and THFA (tetrahydrofolic acid) or for dopamine formation (from L-dopa) such as pyridoxal phosphate will lower the enzymes’ activity. This is evident in individuals with Parkinson’s disease in which the activity of either tyrosine 3-monooxgenase or dopa decarboxylase are as low as 20% (or less).The lack of one or more of the substrates also contributes to the damage of dopaminergic neurons by highly toxic superoxide anion produced by the resulting faulty reaction. 

5 comments:

  1. Hi Ben and Dan! :)

    I was wondering what sort of environmental factors can contribute to the development of Parkinson's Disease?

    And can people develop Parkinson's at a younger age? 'Cause most people with the disease seem to be quite old...

    Thank you! :) Good read! The bit about deep brain stimulation's so cool ~

    ReplyDelete
    Replies
    1. Supp Wei Lu! Environmental factors such as prolonged exposure to certain chemicals such as certain insecticides, herbicides and the fungicide may cause parkinsonism. Some research also shows that rural living, well water, and manganese are associated with Parkinson's disease.
      Young people (21-45 years old) can develop the disease as well especially when it is hereditary. They are diagnosed with young onset Parkinson's disease, or early onset Parkinson’s. The symptoms and their progressions however are not as bad as the symptoms of old people suffering the disease.

      Delete
  2. What type of enzyme is tyrosine 3-monoxygenase? (Transferase/oxidireductase etc)
    And does any of the enzymes require cofactors to work?

    ReplyDelete
    Replies
    1. Supp Ken! Tyrosine 3-monoxygenase belongs to the family of transferases, that is they would transfer phosphate groups to the side-chain oxygen atoms of serine or threonine residues in proteins. Yes it requires cofactors THFA (tetrahydrofolic acid) and pyridoxal phosphate for the reaction to occur.

      Delete
  3. This comment has been removed by the author.

    ReplyDelete