# MITOCHONDRIAL ELECTRON TRANSPORT IN AFRICAN TRYPANOSOMES

> **NIH NIH R01** · NEW YORK UNIVERSITY · 1993 · $205,635

## Abstract

Energy production in the rapidly dividing forms of pathogenic African
trypanosomes is totally dependent upon glycolysis.  This normally
depends on an unusual mitochondrial electron transport system and when
this is not operating on an unusual method of glycerol production.  In
the long slender bloodstream trypanosome tbe electron transport system
contains only two enzymes, glycerol-3-phosphate dehydrogenase and the
trypanosome alternative oxidase (TAO).  The TAO and the production of
glycerol are two metabolic steps not shared by the host but essential to
the parasite.  These steps are, therefore, ideal targets for
chemotherapy. The production of glycerol is thought to be by a reversal
of glycerol kinase but little is known of the TAO other than its
similarity to the alternative oxidase of some higher plants, fungi and
algae.  For this reason, we plan a study of the TAO and its inhibitors.
The information gained is expected to allow clear biochemical
differences between host and parasite to be exploited leading to a
highly selective therapy.

Trypanosoma brucei brucei will be used as a model to achieve two primary
objectives.  The first is to isolate, characterize, and finally
reconstitute the electron transport system.  The second is to evaluate a
limited number of inhibitors for utility as drug candidates.

The glycerol-3-phosphate dehydrogenase and the TAO components of the
electron transport chain will be released from the mitochondrial
membranes of T. b. brucei bloodstream cells.  They will be separated and
then a functioning system will be reconstituted from the isolated
components.  A study will be made of the mechanism whereby the oxidase
component of the chain is inhibited, the resulting information being
used in the eventual design of improved inhibitors.

A promising lead for a practical inhibitor of the TAO has developed: the
N-n-alkyl 3,4dihydroxybenzamides.  A high cure rate has been achieved
with one of these, N-n-butyl 3,4dihydroxybenzamide.  This compound will
be evaluated further and several closely related compounds will be
examined for utility as chemotherapeutic agents.

## Key facts

- **NIH application ID:** 3127522
- **Project number:** 5R01AI017899-06
- **Recipient organization:** NEW YORK UNIVERSITY
- **SAM.gov UEI:** NX9PXMKW5KW8
- **Principal Investigator:** ALLEN B CLARKSON JR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $205,635
- **Award type:** 5
- **Project period:** 1983-04-01 → 1993-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127522

## Citation

> US National Institutes of Health, RePORTER application 3127522, MITOCHONDRIAL ELECTRON TRANSPORT IN AFRICAN TRYPANOSOMES (5R01AI017899-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127522. Licensed CC0.

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