PMID- 20487290
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20100521
IS  - 1365-2958 (Electronic)
IS  - 0950-382X (Linking)
VI  - 75
IP  - 4
DP  - 2010 Feb
TI  - Plasmodium pyruvate dehydrogenase activity is only essential for the parasite's 
      progression from liver infection to blood infection.
PG  - 957-71
LID - 10.1111/j.1365-2958.2009.07034.x [doi]
AB  - Plasmodium parasites possess a single pyruvate dehydrogenase (PDH) enzyme complex 
      that is localized to the plastid-like organelle known as the apicoplast. Unlike 
      most eukaryotes, Plasmodium parasites lack a mitochondrial PDH. The PDH complex 
      catalyses the conversion of pyruvate to acetyl-CoA, an important precursor for 
      the tricarboxylic acid cycle and type II fatty acid synthesis (FAS II). In this 
      study, using a rodent malaria model, we show that the PDH E1 alpha and E3 
      subunits colocalize with the FAS II enzyme FabI in the apicoplast of liver stages 
      but are not significantly expressed in blood stages. Deletion of the E1 alpha or 
      E3 subunit genes of Plasmodium yoelii PDH caused no defect in blood stage 
      development, mosquito stage development or early liver stage development. 
      However, the gene deletions completely blocked the ability of the e1 alpha(-) and 
      e3(-) parasites to form exo-erythrocytic merozoites during late liver stage 
      development, thus preventing the initiation of a blood stage infection. This 
      phenotype is similar to that observed for deletions of genes involved in FAS II 
      elongation. The data strongly support the hypothesis that the sole role of PDH is 
      to provide acetyl-CoA for FAS II.
FAU - Pei, Ying
AU  - Pei Y
AD  - Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, 
      Seattle, WA 98109, USA.
FAU - Tarun, Alice S
AU  - Tarun AS
FAU - Vaughan, Ashley M
AU  - Vaughan AM
FAU - Herman, Rob W
AU  - Herman RW
FAU - Soliman, Joanne M B
AU  - Soliman JM
FAU - Erickson-Wayman, Alyssa
AU  - Erickson-Wayman A
FAU - Kappe, Stefan H I
AU  - Kappe SH
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Mol Microbiol
JT  - Molecular microbiology
JID - 8712028
RN  - EC 1.2.4.1 (Pyruvate Dehydrogenase (Lipoamide))
RN  - EC 1.8.1.4 (Dihydrolipoamide Dehydrogenase)
SB  - IM
MH  - Animals
MH  - Dihydrolipoamide Dehydrogenase/genetics/*metabolism
MH  - Erythrocytes/parasitology
MH  - Female
MH  - Liver/parasitology
MH  - Malaria/parasitology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Organisms, Genetically Modified
MH  - Plasmodium yoelii/*enzymology/genetics/growth & development/metabolism
MH  - Plastids/metabolism
MH  - Pyruvate Dehydrogenase (Lipoamide)/genetics/*metabolism
EDAT- 2010/05/22 06:00
MHDA- 2010/07/31 06:00
CRDT- 2010/05/22 06:00
PHST- 2010/05/22 06:00 [entrez]
PHST- 2010/05/22 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
AID - MMI7034 [pii]
AID - 10.1111/j.1365-2958.2009.07034.x [doi]
PST - ppublish
SO  - Mol Microbiol. 2010 Feb;75(4):957-71. doi: 10.1111/j.1365-2958.2009.07034.x.