N-acetyl D-glucosamine stimulates growth in procyclic forms of Trypanosoma brucei by inducing a metabolic shift
N-acetyl D-glucosamine stimulates growth in procyclic forms of Trypanosoma brucei by inducing a metabolic shift
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N- 乙酰 D-氨基葡萄糖通过诱导代谢转变刺激原环状布氏锥虫的生长
DOI：
10.1017/s0031182008004241
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发表时间：
2008-04-01
期刊：
影响因子：
2.4
通讯作者：
Barrett, M. P.
中科院分区：
文献类型：
--
作者：
Ebikeme, C. E.;Peacock, L.;Barrett, M. P.
已知凝集素抑制糖d -氨基葡萄糖（GlcN）和n-乙酰基d -氨基葡萄糖（GlcNAc）可增强采采蝇媒介对布氏锥虫感染的易感性。在没有任何来自果蝇的因子的情况下，GlcNAc也能在体外刺激锥虫的生长。在这里，我们表明GlcNAc不能被用作直接的能量来源，也不能被锥虫内化。然而，它确实通过与己糖转运体结合来抑制葡萄糖的摄取。d -葡萄糖的缺失导致代谢从主要基于底物水平的d -葡萄糖磷酸化转变为主要基于l -脯氨酸氧化磷酸化的更有效的代谢。原环型锥虫在缺乏d -葡萄糖的培养基中比在富含d -葡萄糖的培养基中生长得更快，密度更高。锥虫使用l -脯氨酸作为能量来源的能力可以根据d -葡萄糖的可用性进行调节，在这里，我们表明这种调节是对d -葡萄糖可用性的分级反应，并由细胞的整体代谢状态决定。因此，在体外，GlcNAc的生长刺激作用似乎与从d -葡萄糖到l -脯氨酸代谢的转换有关。然而，在采采蝇中，GlcNAc的作用似乎独立于这种开关，因为对脯氨酸生长的预适应对采采蝇的感染率没有影响。
The lectin-inhibitory sugars D-glucosamine (GlcN) and N-acetyl D-glucosamine (GlcNAc) are known to enhance susceptibility of the tsetse fly vector to infection with Trypanosoma brucei. GlcNAc also stimulates trypanosome growth in vitro in the absence of any factor derived from the fly. Here, we show that GlcNAc cannot be used as a direct energy source, nor is it internalized by trypanosomes. It does, however, inhibit glucose uptake by binding to the hexose transporter. Deprivation of D-glucose leads to a switch from a metabolism based predominantly on substrate level phosphorylation of D-glucose to a more efficient one based mainly on oxidative phosphorylation using L-proline. Procyclic form trypanosomes grow faster and to higher density in D-glucose-depleted medium than in D-glucose-rich medium. The ability of trypanosomes to use L-proline as an energy source can be regulated depending upon the availability of D-glucose and here we show that this regulation is a graded response to D-glucose availability and determined by the overall metabolic state of the cell. It appears, therefore, that the growth stimulatory effect of GlcNAc in vitro relates to the switch from D-glucose to L-proline metabolism. In tsetse flies, however, it seems probable that the effect of GlcNAc is independent of this switch as pre-adaptation to growth in proline had no effect on tsetse infection rate.