Biochemistry of the non-mevalonate isoprenoid pathway

Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-ᴅ-xylulose 5- phosphate / 2-C-methyl-ᴅ-erythritol 4-phosphate pathway (DOXP/MEP pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway are potential targets for new classes of herbicides. Since the DOXP/MEP pathway also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis, and in the malaria parasite Plasmodium falciparum, all inhibitors and potential herbicides of the DOXP/MEP pathway in plants are also potential drugs against pathogenic bacteria and the malaria parasite. Plants with their easily to handle DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against pathogenic bacteria and the malaria parasite as no particular security measures are required. In fact, the antibiotic herbicide fosmidomycin specifically inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria and in the parasite P. falciparum, and cures malaria-infected mice. This is the first successful application of a herbicide of the novel isoprenoid pathway as a possible drug against malaria.

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Control of Rab5 and Rab7 Expression by the Isoprenoid Pathway

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1998.9007 ◽

1998 ◽

Vol 248 (3) ◽

pp. 469-472 ◽

Cited By ~ 17

Author(s):

Chiara Laezza ◽

Cecilia Bucci ◽

Mariarosaria Santillo ◽

Carmelo B. Bruni ◽

Maurizio Bifulco

Keyword(s):

Isoprenoid Pathway

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Hypothalamic digoxin-mediated model for epileptogenesis

Acta Neuropsychiatrica ◽

10.1034/j.1601-5215.2003.00020.x ◽

2003 ◽

Vol 15 (3) ◽

pp. 115-121 ◽

Cited By ~ 2

Author(s):

Ravi Kumar Kurup ◽

Parameswara Achutha Kurup

Keyword(s):

Dermatan Sulfate ◽

Reductase Activity ◽

Serum Magnesium ◽

Seizure Disorder ◽

Total Serum ◽

Total Serum Cholesterol ◽

Membrane Composition ◽

Isoprenoid Pathway ◽

Rbc Membrane ◽

Age Related

Background/aims:This study assessed the changes in the isoprenoid pathway and its metabolites in seizure disorder (ILAE classification – I generalized – idiopathic generalized epilepsy with age-related onset – epilepsy with generalized tonic clonic seizures on awakening) and the metabolic cascade produced by isoprenoid pathway dysregulation.Methods:The following parameters were assessed in seizure disorder: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugates metabolism and red blood cell (RBC) membrane composition.Results:There was elevation in plasma HMG-CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na-K+ATPase activity, serum magnesium and ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine and quinolinic acid were elevated while tyrosine, dopamine, morphine and norepinephrine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulfate), the activity of glycosaminoglycans (GAG) degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. Total serum cholesterol, LDL cholesterol and free fatty acids were increased while HDL cholesterol and triglycerides were unaltered. The concentration of membrane hexose, fucose, cholesterol and phospholipids in the RBC membrane decreased significantly but the total RBC membrane GAG was unaltered.Conclusions:Epileptogenesis could be due to a dysfunctional isoprenoidal pathway and paroxysmal hypothalamic digoxin hypersecretion.

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Functional Gene Network of Prenyltransferases in Arabidopsis thaliana

Molecules ◽

10.3390/molecules24244556 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4556 ◽

Cited By ~ 1

Author(s):

Diana Kopcsayová ◽

Eva Vranová

Keyword(s):

Arabidopsis Thaliana ◽

Amino Acid Level ◽

Chain Elongation ◽

Pathway Network ◽

Isoprenoid Pathway ◽

Prenyl Diphosphate ◽

Mutant Complementation

Prenyltransferases (PTs) are enzymes that catalyze prenyl chain elongation. Some are highly similar to each other at the amino acid level. Therefore, it is difficult to assign their function based solely on their sequence homology to functional orthologs. Other experiments, such as in vitro enzymatic assay, mutant analysis, and mutant complementation are necessary to assign their precise function. Moreover, subcellular localization can also influence the functionality of the enzymes within the pathway network, because different isoprenoid end products are synthesized in the cytosol, mitochondria, or plastids from prenyl diphosphate (prenyl-PP) substrates. In addition to in vivo functional experiments, in silico approaches, such as co-expression analysis, can provide information about the topology of PTs within the isoprenoid pathway network. There has been huge progress in the last few years in the characterization of individual Arabidopsis PTs, resulting in better understanding of their function and their topology within the isoprenoid pathway. Here, we summarize these findings and present the updated topological model of PTs in the Arabidopsis thaliana isoprenoid pathway.

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