| ACSL1 |
Acyl-CoA synthetase 1 (ACS1), or long-chain-fatty-acid-CoA
ligase 1, is an isozyme of the long-chain fatty-acid-coenzyme A ligase
family. ACSL1 activates free long-chain fatty acids, coming from an
exogenous or endogenous source, which is the first reaction of their
metabolism to fatty acyl-CoA esters, and this activation is required
for both synthesis of cellular lipids as part of anabolic lipid metabolism
and their degradation via β-oxidation as part of catabolic lipid
metabolism. The carbohydrate and lipid metabolisms were the most altered
pathways in response to Leishmania infection,
as the parasite could exploit the host’s organelles to obtain
energy.64 Although not strictly related
to drug resistance, due to its metabolic relevance it has gained interest
as a drug target for antileishmanial therapies.65
|
| TAP1 |
Transporter
associated with antigen processing 1 is also known
as transporter 1, ATP binding cassette subfamily B member. TAP1 is
a member of the superfamily of ATP-binding cassette (ABC) transporters;
therefore, it is additionally denoted as ABCB2. The ABC transporters
are also associated with antigen processing (TAP) and adaptive immunity.
TAP1 seems to have an important role in antigen presenting in parasitic
diseases, including Leishmania major and Toxoplasma gondii.66,67
|
| NDK3 |
Members of the nucleoside
diphosphate kinase (NDK) family are
ubiquitous and reversibly convert nucleoside diphosphates to the corresponding
nucleoside triphosphates by transferring to the former the phosphate
in the γ-position from another nucleoside triphosphate. The
reaction is Mg2+-dependent and proceeds by a ping-pong
mechanism that involves an intermediate activated state containing
a phosphorylated histidine. NDK enzymes play a fundamental role in Leishmania infection since the parasite lacks the
ability to synthesize purine nucleotides de novo and
takes advantage of its host’s enzymes to survive and proliferate.
Its overexpression relates to the parasite’s need for nucleoside
supply.68
|
| GM2A |
Ganglioside GM2 activator protein is a liposomal protein that
catalyzes degradation of glycosphingolipids with terminal α-galactosyl
residues in most non-neuronal tissues and in body fluids. The large
binding pocket can accommodate several single-chain phospholipids
and fatty acids, and GM2A also exhibits some calcium-independent phospholipase
activity. It binds gangliosides and stimulates ganglioside GM2 degradation.
It stimulates only the breakdown of ganglioside GM2 and glycolipid
GA2 by β-hexosaminidase A. It extracts single GM2 molecules
from membranes and presents them in soluble form to β-hexosaminidase
A for cleavage of N-acetyl-d-galactosamine
and conversion to GM3 (by similarity). It also has cholesterol transfer
activity.69 Although phospholipid and sphingolipid
metabolism are important in leishmania,58 a connection of GM2A with the pathway has not been shown. |
| PDHX |
The protein PDHX represents a
small portion of the pyruvate
dehydrogenase (PDH) complex. This complex is located in the mitochondrial
matrix and is responsible for the utilization of pyruvate, derived
from glucose through glycolysis, in most cells and its conversion
to acetyl-CoA and carbon dioxide in the central phase of the Krebs
cycle.70,60
|
| TFRC |
The transferrin receptor C (TFRC), also known as CD71, is an
integral membrane glycoprotein, ubiquitously expressed, consisting
of two identical subunits linked by disulfide bridges. TFRC uptakes
iron by endocytosis of the ligand-occupied transferrin and regulates
intracellular iron homeostasis.86 Human
TFRC has not been related to parasitic infections yet, but its contribution
to iron metabolism suggests that - as for transferrin and lactoferrin
- it could be employed by the parasite as a source of nutrient intake. |
