This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Around the world, trypanosomatids are known for being etiological agents of several highly disabling and often fatal diseases like Chagas disease Trypanosoma cruzileishmaniasis Leishmania spp.
Throughout their life cycle, they must cope with diverse environmental conditions, and the mechanisms involved in these processes are crucial for their survival. In this review, we describe the role of heme in several essential metabolic pathways of these protozoans.
Notwithstanding trypanosomatids lack of the complete heme biosynthetic pathway, we focus our discussion in the metabolic role played for important heme-proteins, like cytochromes. Although several genes for different types of cytochromes, involved in mitochondrial respiration, polyunsaturated fatty acid metabolism, and sterol biosynthesis, are annotated at the Tritryp Genome Project, the encoded proteins have not yet been deeply studied.
We pointed our attention into relevant aspects of these protein functions that are amenable to be considered for rational design of trypanocidal agents.
The life cycle of these trypanosomatids is complex, presenting several developmental stages in different hosts. They have developed a digenetic life cycle with one or several vertebrate hosts and a hematophage insect vector that allows the transmission between them.
A direct consequence is the environmental changes suffered among their life cycle thus, they have to adapt their metabolism to different nutrient availability [ 2 ]. Another feature of these parasites is the presence of nutritional requirements for several essential cofactors where heme is included.
Heme plays a fundamental role in many cellular processes. It is an essential cofactor for proteins involved in oxygen transport and storage hemoglobin and myoglobinmitochondrial electron transport Complex II—IVdrug and steroid metabolism cytochromessignal transduction nitric oxide synthases, soluble guanylate cyclasesand transcription and regulation of antioxidant-defense enzymes.
Heme is also a regulatory molecule; its cytosolic to nuclear ratio and the absolute amount of its concentration affects gene transcription and translation; thus, the intracellular heme level must be tightly regulated [ 45 ].
Hence, these trypanosomatids are dependent on the uptake of this compound from their hosts. After being imported, heme is transported and inserted into target heme-proteins, which are distributed throughout different subcellular compartments.
It is not well understood how these organisms acquire heme and how this cofactor is distributed inside the cell. However, they contain heme-proteins-like cytochromes, involved in essential metabolic pathways.
This review will be focused in the presence and role of relevant heme-proteins in trypanosomatids. Heme General Features Heme is an essential molecule for most archaea, bacteria, and eukaryotes.
Moreover, since the growth of bacteria and plants rely on the correct formation of tetrapyrroles, their corresponding biosynthetic pathways are attractive targets for antibacterial drug development and herbicide treatment [ 7 — 9 ]. The free living nematode Caenorhabditis elegans lacks the complete heme biosynthetic pathway; it feeds on bacteria and thus has easy access to heme [ 10 ].
The majority of the porphyrins contain iron as the central metal ion. The most abundant heme is heme B or protohemeand it is found in nearly all the heme-proteins such as hemoglobin, myoglobin, and so forth.
The tetrapyrrol structure of heme B contains two propionate, two vinyl and four methyl side chains Figure 1. The oxidation of the methyl side chain to a formyl group and the substitution of a vinyl side chain with a carbon isoprenoid side chain convert heme B into heme A, the prosthetic group of the mitochondrial cytochrome c oxidase and of the several bacterial terminal oxidase.
C-type hemoproteins, such as cytochrome c and bc1 complex, contain heme c in which the two vinyl side chains of the heme B are covalently attached to the protein Figure 1. For almost all organisms, hemes are essential components of their energy recovering electron transport chains and cofactors for several proteins.
Many enzymes like peroxidases, catalases, and the large group of cytochrome P also rely on heme as a prosthetic group.
Heme-proteins can furthermore serve as sensors for diatomic gases such as O2, CO, and NO and for CO2 in signal transduction pathways [ 4 ].
Schematic view of different hemes biosynthesis pathways in S. Adapted from Moraes et al. Heme Biosynthesis The heme biosynthetic pathway is highly conserved through evolution [ 312 ].
It is present in most organisms but differs in the synthesis of the first precursor, delta-aminolevulinic acid ALA. The remaining seven steps of the pathway from ALA to heme B are carried out by the same enzymes in all organisms [ 1213 ].
Eukaryotes differ also in the intracellular localization of individual enzymatic steps.Bax-induced permeabilization of the mitochondrial outer membrane and release of cytochrome c are key events in apoptosis.
We describe the purification of a H 2 O-producing NADH oxidase from the protozoan parasite Giardia duodenalis.
The enzyme is a monomeric flavoprotein containing flavin adenine dinucleotide in a molar ratio with the polypeptide. BSc Waterloo PhD University of British Columbia Postdoctoral Fellow, UBC Postdoctoral Fellow, Laboratory of Host Defenses NIAID NIH, All of our Board Certified Medical Physicians and Doctors are expert specialists in prescribing HGH, Testosterone, Sermorelin, and HCG Weight Loss Diet.
G. al. Giardia intestinalis.
). five to six morphologically distinct species are recognised (Meyer and Radulescu. ). microti from voles (Adam. lamblia can be distinguished from other Giardia species because it has two vertical adhesion disks on the top of the body which allows it to attach to the hosts small intestine and retain nutrients from the host.
G. Giardia lamblia infect humans and other . One of the most common and studied is transmitted by the microscopic protozoan, Giardia intestinalis, also known as G.
lamblia and G. duodenalis (Ivanov, ). This eukaryotic parasite is responsible for the transmission of the most common waterborne disease, giardiasis, which causes watery diarrhea, vomiting, and has even been linked to irritable bowl syndrome (Ankarklev et.