Citrate and Isocitrate Utilization by Rat Ventral Prostate
Mitochondria

Costello, Leslie C.; Fadika, G.O.; Franklin, Ronald B.

doi:10.1159/000458573

Cited by 9 publications

(5 citation statements)

References 2 publications

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“…However, in normal prostate epithelial cells citrate is predominantly an end-product of intermediary metabolism, rather than an utilizable intermediate as in most other cells. It is well established that citrate-producing prostate cells and their mitochondria readily oxidize isocitrate, but not citrate [ 7 - 9 , 20 ]. These collective observations establish that the accumulation of citrate in citrate-producing prostate cells is predominantly due to a limiting m-aconitase activity (for additional supporting evidence see [ 1 - 4 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, citrate-producing normal prostate glands and hyperplastic glands exhibit a citrate/isocitrate ratio ~30/1; which is indicative of a limiting m-aconitase activity [ 1 , 7 ]. This is substantiated by the impaired citrate oxidation but not isocitrate oxidation by citrate-accumulating prostate cells [ 8 , 9 ]. A limited m-aconitase activity could be the result of an inhibition of the enzyme and/or a decrease in the level of the enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues

et al. 2006

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Background: In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism that is essential to prostate malignancy. The limiting m-aconitase activity in prostate epithelial cells could be the result of a decreased level of m-aconitase enzyme and/or the inhibition of existing maconitase. Earlier studies identified zinc as an inhibitor of m-aconitase activity in prostate cells; and that the depletion of zinc in malignant cells is an important factor in this metabolic transformation. However, a possibility remains that an altered expression and level of m-aconitase enzyme might also be involved in this metabolic transformation. To address this issue, the in situ level of m-aconitase enzyme was determined by immunohistochemical analysis of prostate cancer tissue sections and malignant prostate cell lines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues

et al. 2006

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“…Anaplerosis and cataplerosis describe reciprocal and correlative reactions that can be dictated by changes in the microenvironment of the cell, such as hypoxia, or in response to extracellular signals, such as hormones or inflammatory stimuli (6,21). However, a concept first proposed in the 1970s (22,23) has now reemerged whereby the Krebs cycle can undergo remodeling to support the nonmetabolic functions of its intermediates and their derivatives. This rewiring is often achieved through modulation of the expression and/or activity of specific Krebs cycle enzymes and both anaplerotic and cataplerotic sequences.…”

Section: Krebs Cycle Rewiringmentioning

confidence: 99%

Krebs Cycle Reborn in Macrophage Immunometabolism

Ryan

O’Neill

2020

Annu. Rev. Immunol.

304

249

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A striking change has happened in the field of immunology whereby specific metabolic processes have been shown to be a critical determinant of immune cell activation. Multiple immune receptor types rewire metabolic pathways as a key part of how they promote effector functions. Perhaps surprisingly for immunologists, the Krebs cycle has emerged as the central immunometabolic hub of the macrophage. During proinflammatory macrophage activation, there is an accumulation of the Krebs cycle intermediates succinate and citrate, and the Krebs cycle–derived metabolite itaconate. These metabolites have distinct nonmetabolic signaling roles that influence inflammatory gene expression. A key bioenergetic target for the Krebs cycle, the electron transport chain, also becomes altered, generating reactive oxygen species from Complexes I and III. Similarly, alternatively activated macrophages require α-ketoglutarate-dependent epigenetic reprogramming to elicit anti-inflammatory gene expression. In this review, we discuss these advances and speculate on the possibility of targeting these events therapeutically for inflammatory diseases.

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“…was assayed by measuring the reduction of NADP using the 340/374 combination [1,5], Citrate oxidation was determined by 14C02 pro duction from 6-14C-citrate. Reactions were performed in the Dubnoff metabolic shaker and l4C02 production measured as described previously [4,10]. Isocitrate was assayed fluoroenzymatically [5,8], and mitochon drial protein was determined by the method of Lowry et al [17],…”

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confidence: 99%

Aconitase Activity, Citrate Oxidation, and Zinc Inhibition in Rat Ventral Prostate

Costello¹,

Franklin²

1981

Enzyme

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Aconitase activity and citrate oxidation were determined in mitochondrial preparations from rat ventral prostate. Aconitase activity in prostate mitochondria was approximately 10% of the activity observed in kidney preparations. The prostate aconitase activity was completely inhibited by the addition of 1.0 mmol/l zinc and kidney aconitase was inhibited by approximately 50%. The presence of 1.0 mmol/l zinc also markedly inhibited the formation of isocitrate from cis-aconitate. The reduction of NADP by citrate was markedly inhibited (approx. 95%) by 1.0 mmol/l zinc as compared with a 70 and 40% inhibition of aconitate - and isocitrate - stimulated reduction, respectively. These results indicate that zinc might be a strong inhibitor of aconitase activity with an inhibitory effect on isocitrate dehydrogenase also. The effect of 1.0 mmol/l zinc on citrate oxidation was studied by determining 14C0(2) production from 6-14C-citrate. 14C0(2) was significantly inhibited by zinc. These results further corroborate the conclusion that citrate accumulation in prostate might be the result of limited citrate oxidation which results from a combination of low aconitase activity and possibly zinc inhibition.

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Citrate and Isocitrate Utilization by Rat Ventral Prostate Mitochondria

Cited by 9 publications

References 2 publications

Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues

Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues

Krebs Cycle Reborn in Macrophage Immunometabolism

Aconitase Activity, Citrate Oxidation, and Zinc Inhibition in Rat Ventral Prostate

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