arachidonic acid pathway

Examples of arachidonic acid pathway in the following topics:

• Fever

  • PGE2 release comes from the arachidonic acid pathway, which also produces inflammatory mediators such as thromboxane and leukotriene.
  • This pathway is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase.
  • Exogenous factors s lipopolysaccharide toxin (from gram negative bacteria) which can activate a number of innate immune activation pathways.
  • These pathways induce the expression of endogenous pyrogens, including a variety of cytokines such as IL1α, IL1β, IL6, TNFα, TNFβ, IFNα, INFβ, and INFγ.
  • When TNFα or any of these cytokine factors bind to cells in phospolipids in the brain, the arachidonic acid pathway is activated and PGE2 released to act on the hypothalamus and cause the fever response.

• Prostaglandins

  • Because their genesis in body tissues is tied to the metabolism of the essential fatty acid arachadonic acid (5,8,11,14-eicosatetraenoic acid) they are classified as eicosanoids.
  • The metabolic pathways by which arachidonic acid is converted to the various eicosanoids are complex and will not be discussed here.
  • It is helpful to view arachadonic acid in the coiled conformation shown in the shaded box.

• Eicosanoids

  • In biochemistry, eicosanoids are signaling molecules made by oxidation of 20-carbon essential fatty acids (EFAs).
  • An excess of ω-6 to ω-3 fatty acids is common in western diets and is thought to encourage certain inflammatory disorders such as arthritis, cardiovascular disease, and cancers of the digestive system.

• Connecting Proteins to Glucose Metabolism

  • Excess amino acids are converted into molecules that can enter the pathways of glucose catabolism.
  • However, if there are excess amino acids, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism.
  • Each amino acid must have its amino group removed (deamination) prior to the carbon chain's entry into these pathways.
  • When deaminated, amino acids can enter the pathways of glucose metabolism as pyruvate, acetyl CoA, or several components of the citric acid cycle.
  • Deaminated amino acids can also be converted into another intermediate molecule before entering the pathways.

• Metabolic Pathways

  • An anabolic pathway requires energy and builds molecules while a catabolic pathway produces energy and breaks down molecules.
  • Consequently, metabolism is composed of these two opposite pathways:
  • One example of an anabolic pathway is the synthesis of sugar from CO2.
  • Other examples include the synthesis of large proteins from amino acid building blocks and the synthesis of new DNA strands from nucleic acid building blocks.
  • Chemical reactions in metabolic pathways rarely take place spontaneously.

• Substrates for Biosynthesis

  • The citric acid cycle, comprised of a series of chemical reactions, provides precursors for additional biochemical pathways.
  • The precursors include amino acids and reducing agents such as NADH.
  • Additional pathways that require precursors formed by the TCA include amino acid and nucleotide synthesis .
  • Additional pathways that require substrates or metabolites produced by the glycolytic pathway include: gluconeogenesis, lipid metabolism, the pentose phosphate pathway, and the TCA.
  • An overview of the glycolytic pathway.

• Chemistry of Hormones

  • Peptide hormones consist of short chains of amino acids, such as vasopressin, that are secreted by the pituitary gland and regulate osmotic balance; or long chains, such as insulin, that are secreted by the pancreas, which regulates glucose metabolism.
  • Lipid and phospholipid-derived hormones are produced from lipids such as linoleic acid and arachidonic acid.
  • Eicosanoids are also lipid hormones that are derived from fatty acids in the plasma membrane.
  • Monoamine hormones are derived from single aromatic amino acids like phenylalanine, tyrosine, and tryptophan.

• Connecting Lipids to Glucose Metabolism

  • Lipids can be both made and broken down through parts of the glucose catabolism pathways.
  • Like sugars and amino acids, the catabolic pathways of lipids are also connected to the glucose catabolism pathways.
  • The lipids that are connected to the glucose pathways are cholesterol and triglycerides.
  • Animals can make most of the fatty acids they need.
  • Triglycerides can be both made and broken down through parts of the glucose catabolism pathways.

• Acetyl CoA and the Citric Acid Cycle

  • The citric acid cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy.
  • The name of this metabolic pathway is derived from citric acid, a type of tricarboxylic acid that is first consumed and then regenerated by this sequence of reactions to complete the cycle.
  • The NADH generated by the TCA cycle is fed into the oxidative phosphorylation pathway.
  • The citric acid cycle is a key component of the metabolic pathway by which all aerobic organisms generate energy.
  • The NADH and QH2 that is generated by the citric acid cycle is used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP).

• Organic Acid Metabolism

  • The most commonly metabolized organic acids are the carboxylic acids, which are organic acids containing at least one carboxyl (-COOH) group.
  • This is a critical late step in the hydrocarbon utilization pathway.
  • This process requires the β-oxidation pathway, a cyclic process that catalyzes the sequential shortening of fatty acid acyl chains to the final product, acetyl-CoA.
  • The fatty acid chain that is left over after the thiolation step can then reenter the β-oxidation pathway, which can cycle until the fatty acid has been completely reduced to acetyl-CoA.
  • Free fatty acids are broken down to acetyl-CoA by dedicated enzymes in the β-oxidation pathway.