Energy metabolism and its regulation in the adult liver fluke<i>Fasciola hepatica</i>

Lloyd, Geoffrey M.

doi:10.1017/s0031182000049957

Cited by 17 publications

(6 citation statements)

References 125 publications

(138 reference statements)

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“…In Fig. 3 ports that fumarate hydratase in F. hepatica is located in the cytosol, our observation that it has a mitochondrial localisation is now generally accepted [11].…”

Section: Pathways Of Acetate Formation the Degradation Of [6-14c]glusupporting

confidence: 53%

Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica

Tielens

Heuvel

Bergh

1987

Molecular and Biochemical Parasitology

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A comparison of glucose catabolism by juvenile and adult liver flukes, Fasciola hepatica, showed that in the adult the cytosolic degradation of glucose via phosphoenolpyruvate carboxykinase (PEPCK) was the most important route, whereas in the freshly excysted juvenile a large part was degraded via pyruvate kinase (PK). However, it was also shown that the adult did not exclusively use the PEPCK pathway, nor did the juvenile exclusively use the PK pathway. When the juvenile was forced to anaerobic functioning it produced propionate and acetate just like the adult, but this did not imply that it switched to the pathways of the adult: the pathway via PK remained important. Malic enzyme (NADP(H)-dependent) was demonstrated to be present in the cytosol and in the mitochondria of both juveniles and adults. These enzyme activities enable the parasite to use a mixture of maiate and pyruvate in any ratio as substrate for the mitochondrial production of propionate and acetate. Pyruvate dismutation was important in the anaerobically functioning juvenile, whereas in the adult malate was the major, but not the only mitochondrial substrate. The pH profiles of PK and PEPCK showed that the pathway of PEP metabolism at the PK/PEPCK branchpoint can be regulated by the pH. However, the end products of glucose breakdown were not dependent on the pH. During its development, the liver fluke will gradually be forced to anaerobic functioning. At first, the acidic end product will favour a partitioning of PEP at the PK/PEPCK branchpoint towards malate formation. Later, a lasting predominance of the PEPCK pathway occurs as PK activity almost completely disappears. During the development of F. hepatica also a transition in the mitochondria occurs: at the acetyl-coenzyme A branchpoint a switch from citrate to acetate formation could be demonstrated. The most likely mechanism of this change is discussed.

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“…In Fig. 3 ports that fumarate hydratase in F. hepatica is located in the cytosol, our observation that it has a mitochondrial localisation is now generally accepted [11].…”

Section: Pathways Of Acetate Formation the Degradation Of [6-14c]glusupporting

confidence: 53%

Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica

Tielens

Heuvel

Bergh

1987

Molecular and Biochemical Parasitology

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“…Nitroxynil is believed to exert its flukicidal activity by the uncoupling of oxidative phosphorylation (Fairweather and Boray 1999), even though this pathway is considered to be of minor importance to the energy budget of the fluke (Lloyd, 1986;Tielens et al 1984). Some of the morphological changes observed in the fluke can be attributed to this action: for example, the swelling of the mitochondria and cisternae of the ger, the decreased secretory activity in the tegumental and gastrodermal cells and the increased autophagic activity in the gut cells.…”

Section: Discussionmentioning

confidence: 99%

Morphological response of triclabendazole-susceptible and triclabendazole-resistant isolates of Fasciola hepatica to treatment in vitro with nitroxynil (Trodax)

et al. 2008

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Adult liver flukes belonging to three isolates of differing sensitivity to triclabendazole were incubated for 24 h in vitro in nitroxynil at a concentration of 100 microg/ml. Fine structural changes to the tegument, sub-tegumental region and gut were assessed by transmission electron microscopy. Similar changes were observed in all three isolates. In the tegumental syncytium, the basal infoldings and mitochondria were swollen, and there was an accumulation and accelerated release of secretory bodies at the apex. The crystalline core of the spines was disrupted, and the tegumental covering sloughed off. Mitochondria in the tegumental cells were also swollen, the Golgi complexes were affected and reduced numbers of T1 secretory bodies were evident in the T1-type of tegumental cell. In the sub-tegumental region, large spaces were present between cells and tissues, indicative of severe internal flooding. Swelling of mitochondria and cisternae of the granular endoplasmic reticulum was seen in the gastrodermal cells, which contained few secretory bodies. The extent of disruption varied between the isolates: the triclabendazole-resistant Sligo isolate was the most severely affected, while the Fairhurst triclabendazole-susceptible isolate was the least affected. In all three isolates, the tegument was more severely affected than the gut.

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“…However, the supporting evidence is not strong (as discussed in "Introduction") and oxidative phosphorylation does not make a significant contribution to the overall energy budget of the fluke (Van Vugt 1979Van den Bergh et al 1980;Lloyd and Barrett 1983;Tielens et al 1984;Lloyd 1986). It is not always possible to link particular morphological changes to uncoupling activity, but such disruption would be compatible with the changes to the mitochondria and ger cisternae, the decreased secretory activity in the gastrodermal cells and the increased number of autophagic vacuoles.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo and in vitro drug treatment with nitroxynil (Trodax)

McKinstry¹,

Brennan²,

Halferty³

et al. 2007

Parasitol Res

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Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of 40 mg/kg, and adult Fasciola hepatica were recovered after 24, 48 and 72 h. Fine structural changes to the tegument and gut were monitored by transmission electron microscopy. Flukes were also incubated for 24 h in vitro in nitroxynil at a concentration of 100 microg/ml. Following treatment in vivo, there was an accumulation and accelerated release of secretory bodies at the apex of the tegumental syncytium. Some swelling of the mucopolysaccharide masses surrounding the basal infolds was evident after 48 and 72 h. There was an initial accumulation of T1 secretory bodies at the base of the syncytium, but this decreased at 72 h, coinciding with a decline in their production in the tegumental cells. The mitochondria were consistently swollen in the tegumental cells. At 72 h, large vacuolations were observed between the muscle layers and there was flooding around the underlying tissues. Some tegumental cells were seen to be degenerating and beginning to disintegrate. After 24 h treatment in vitro, the basal infolds were swollen and the crystalline structure of the spines was disrupted. Flooding of the internal tissues was evident and, in the tegumental cells, Golgi complexes and secretory bodies were absent. The mitochondria in the tegumental cells were swollen. In the gastrodermal cells, changes were evident at the earliest time period in vivo. The lamellae were disrupted, few secretory bodies were present, the mitochondria and cisternae of granular endoplasmic reticulum (ger) were swollen and there was an increased number of secretory bodies. These changes became progressively more severe with time. Similar changes were evident following treatment in vitro; vesiculation of the ger was also seen. The results indicate that oral uptake is the predominant route of entry of nitroxynil into the fluke.

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Energy metabolism and its regulation in the adult liver flukeFasciola hepatica

Cited by 17 publications

References 125 publications

Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica

Differences in intermediary energy metabolism between juvenile and adult Fasciola hepatica

Morphological response of triclabendazole-susceptible and triclabendazole-resistant isolates of Fasciola hepatica to treatment in vitro with nitroxynil (Trodax)

Ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo and in vitro drug treatment with nitroxynil (Trodax)

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