Oxidation of leucine by Leishmania donovani.
The metabolism of leucine by Leishmania donovani was investigated. Washed promastigotes were incubated with [1-14C]- or [U-14C]leucine or [1-14C]alpha-ketoisocaproate (KIC) and 14CO2 release was measured. The amount of KIC-derived acetyl-CoA oxidized in the citric acid cycle was computed. Promastigotes from mid-stationary phase cultures oxidized each of these labeled substrates less rapidly than cells from late log phase cultures, and significantly less acetyl-CoA derived from KIC oxidation was oxidized in the citric acid cycle. Glucose was a stronger inhibitor than was acetate of CO2 formation in the citric acid cycle in log phase promastigotes, but the reverse was observed in cells from mid-stationary phase. Alanine also inhibited leucine catabolism, but glutamate had little effect. Acute hypo-osmotic stress did not affect leucine catabolism, but hyper-osmotic stress caused appreciable inhibition of leucine oxidation. Cells grown under hypo- or hyper-osmotic conditions showed no changes in the effects of hypo- or hyper-osmotic stress on leucine catabolism, i.e. L. donovani is not an osmoconformer with respect to leucine metabolism. Leucine utilization in L. donovani was insensitive to a number of drugs that affect leucine metabolism in mammalian cells, indicating that the leucine pathway in L. donovani is not regulated in the same manner as in mammalian cells.
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
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JJ
Blum
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000085:Acetates / Q000494:pharmacology; D000090:Acetoacetates / Q000378:metabolism; D000409:Alanine / Q000494:pharmacology; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007651:Keto Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism; D007893:Leishmania donovani / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009997:Osmotic Pressure; D010084:Oxidation-Reduction
D000085:Acetates; D000090:Acetoacetates; D005971:Glutamates; D007651:Keto Acids; D009097:Multienzyme Complexes; D018698:Glutamic Acid; C016635:acetoacetic acid; C013082:alpha-ketoisocaproic acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D007930:Leucine; D005947:Glucose; D000409:Alanine