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Pathway Description
Mitochondrial Beta-Oxidation of Medium Chain Saturated Fatty Acids
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-08-16
Beta-oxidation is the major degradative pathway for fatty acid esters in humans. Fatty acids and their CoA esters are found throughout the body, playing roles such as components of cellular lipids, regulators of enzymes and membrane channels, ligands for nuclear receptors, precursor molecules for hormones, and signalling molecules. Beta-oxidation occurs in the peroxisomes and mitochondria, the latter of which is depicted here. Whether beta-oxidation starts in the mitochondria or the peroxisome depends on the length of the fatty acid. Medium to long chain fatty acids go directly to the mitochondria, whereas very long chain fatty acids (>22 carbons) may be first metabolized down to octanyl-CoA in the peroxisomes and then transported to the mitochondria for the remainder of the oxidation. Beta-oxidation begins with activation of fatty acids by an acyl-coenzyme A synthetase. ATP is used to produce reactive fatty acyl adenylate that can then react with coenzyme A to produce a fatty acyl-CoA. Short and medium chain fatty acids can enter the mitochondria directly via diffusion where they are activated in the mitochondrial matrix by acyl-coenzyme A synthetases. In the first step of the beta-oxidation cycle, a double bond between C-2 and C-3 is formed, producing a trans-Δ2-enoyl-CoA. This is catalyzed by acyl-CoA-dehydrogenases in the mitochondria, which have forms specific to the different lengths of fatty acids. In the second step, enoyl CoA hydratase hydrates the newly formed double bond between C-2 and C-3, producing an L-beta-hydroxyacyl CoA. Next, L-beta-hydroxyacyl CoA dehydrogenase converts the hydroxyl group into a keto group, producing a beta-ketoacyl CoA. In the fourth and final step, the enzyme beta-ketothiolase cleaves the β-ketoacyl CoA and inserts the thiol group of another CoA between C-2 and C-3, reducing the acyl-CoA by 2 carbons and generating acetyl-CoA. The final two steps also have enzymatic forms specific to short chain fatty acids. Additionally, there is a trifunctional protein complex with enzymatic activity capable of performing all of the final 3 steps (hydratase, dehydrogenase, thiolase) in medium to very long chain fatty acids. This four step cycle repeats, removing 2 carbons from the fatty acid each time until it becomes acetyl-CoA. Acetyl-CoA is necessary for the citric acid cycle, among other cellular processes.
References
Mitochondrial Beta-Oxidation of Medium Chain Saturated Fatty Acids References
Vessey DA, Lau E, Kelley M: Isolation and sequencing of cDNAs for the XL-I and XL-III forms of bovine liver xenobiotic-metabolizing medium-chain fatty acid:CoA ligase. J Biochem Mol Toxicol. 2000;14(1):11-9.
Pubmed: 10561077
Fujiwara K, Takeuchi S, Okamura-Ikeda K, Motokawa Y: Purification, characterization, and cDNA cloning of lipoate-activating enzyme from bovine liver. J Biol Chem. 2001 Aug 3;276(31):28819-23. doi: 10.1074/jbc.M101748200. Epub 2001 May 29.
Pubmed: 11382754
Kasuya F, Tatsuki T, Ohta M, Kawai Y, Igarashi K: Purification, characterization, and mass spectrometric sequencing of a medium chain acyl-CoA synthetase from mouse liver mitochondria and comparisons with the homologues of rat and bovine. Protein Expr Purif. 2006 Jun;47(2):405-14. doi: 10.1016/j.pep.2005.11.006. Epub 2005 Dec 5.
Pubmed: 16378734
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
Pubmed: 16305752
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000481
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