Research Notes: Citrate Synthase

Mol Cell Endocrinol. 2007 Mar 15.
Altered lipid catabolism in the vitamin A deficient liver.
Kang HW, Bhimidi GR, Odom DP, Brun PJ, Fernandez ML, McGrane MM.
Departments of Nutritional Sciences and Molecular and Cellular Biology, The University of Connecticut, 3624 Horsebarn Hill Road Extension, Storrs, CT, USA.

The transcriptome pattern of metabolic genes in vitamin A deficient (VAD) liver has been compared to the vitamin A-sufficient (VAS) state using the Mouse 32k oligonucleotide (70mer) array. In VAD liver there was a decrease in expression of genes encoding enzymes of mitochondrial fatty acid (FA) oxidation; these genes included fatty acyl CoA ligase, carnitine o-palmitoyl transferase 1, medium chain acyl-CoA dehydrogenase, 3-ketoacyl CoA thiolase, and citrate synthase. Particularly affected was peroxisome metabolism, as genes encoding enzymes of peroxisomal FA oxidation and transport proteins were differentially expressed. These genes included those encoding acyl-CoA oxidase 1, the peroxisomal bifunctional enzyme, peroxisomal thiolase, and carnitine o-octanoyl transferase, the enzyme involved in shuttling FAs from the peroxisome to the mitochondrion. Most genes that were differentially expressed with chronic vitamin A depletion were responsive to treatment with all-trans retinoic acid (RA). Consistent with the decreased expression of genes involved in FA oxidation, we found an increase in hepatic macrocytic lipid accumulation and triglyceride levels. The relevant nuclear receptor gene that was differentially expressed in the VAD liver was that encoding the peroxisome proliferator-activated receptor (PPAR) alpha, the mRNA levels for which were decreased in VAD liver and increased with all-trans RA treatment. Down regulation of the PPAR alpha gene is the likely cause of the altered expression pattern of the above metabolic genes in VAD liver.

Med Hypotheses. 2007 Mar 15.
The biological significance of cancer: Mitochondria as a cause of cancer and the inhibition of glycolysis with citrate as a cancer treatment.
Halabe Bucay A.
Hospital Angeles Lomas, Av Vialidad de la Barranca s/n, Huixquilucan, Mexico.

In this article, I present the hypothesis that cancer presents due to the domination of the cell by mitochondria, which, from an evolution viewpoint, appeared in multi-cellular living being with the incorporation of a bacteria into a primitive cell, the bacteria sustained itself as mitochondria and these conserved their identity and bacterial characteristics, based on this, the hypothesis is suggested of the biological competition between the cell and the mitochondria; the mitochondria, on establishing itself as an independent entity within the cell, created the need to permanently remain in the cytoplasm of the cell, thus, from an energy viewpoint, when a cell becomes malignant, the mitochondria are the sole beneficiaries, as there is an ideal environment at the cellular level for the mitochondria to sustain their functions, and from this hypothesis, the treatment for fighting cancer consists of inhibiting glycolysis, being the principal source of energy for the mitochondria, this is achieved by administering citrate to cancer patients, as the citrate inhibits the phosphofructokinase enzyme, the pyruvate dehydrogenase complex and the succinate dehydrogenase enzyme of Krebs cycle, thus, the mitochondria will be forced to limit their metabolism and, secondarily, will lower the reproduction capacity of the cell in general.