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Related Concept Videos

The Citric Acid Cycle: Output01:28

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The citric acid cycle is termed an amphibolic pathway as it operates both anabolically and catabolically. The cyclic reactions balance the flux of the substrates to provide an optimal concentration of NADH and ATP to the cell.
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In aerobic organisms, the citric acid cycle is the second stage of cellular respiration wherein molecules derived from the breakdown of carbohydrates, proteins, and fats are oxidized into carbon dioxide and energy. This process is also known as the tricarboxylic acid (TCA) cycle as the first product of the cycle, citric acid, contains three carboxyl groups in its structure. Alternatively, this cycle is also referred to as the Krebs cycle, in honor of its discoverer Sir Hans Krebs.
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Extracellular Citrate in Health and Disease.

M E Mycielska1, V M Milenkovic, C H Wetzel

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Citrate, vital for metabolism, plays key roles in sperm energy, neuronal function, and cancer metastasis. Understanding citrate transporters could lead to new therapies for infertility, mental disorders, and cancer.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolomics

Background:

  • Citrate is a crucial intracellular metabolic substrate with varying extracellular levels.
  • Decreased citrate levels are linked to male infertility, neurological disorders, and metastatic cancer.
  • Extracellular citrate's role in specialized cells and its transport mechanisms are not well understood.

Purpose of the Study:

  • To review the role of citrate as an energy substrate for sperm.
  • To examine the function of astrocyte-released citrate in neuronal operation and its implications for mental disorders.
  • To explore citrate's role in cancer cell metabolism and metastasis.

Main Methods:

  • Literature review of metabolomics research.
  • Analysis of studies on citrate levels in blood, urine, and tissues of cancer patients.
  • Discussion of citrate's physiological and pathophysiological roles.

Main Results:

  • Citrate serves as an energy source for sperm.
  • Astrocyte-derived citrate is essential for normal neuronal function.
  • Extracellular citrate may fuel cancer cell metabolism, supporting metastasis.

Conclusions:

  • Citrate transporters in astrocytes, sperm, and cancer cells are potential therapeutic targets.
  • Pharmacological regulation of citrate transport could offer treatments for infertility, mental diseases, and cancer.