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.
Blum
J J
JJ
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
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