The β- oxidation pathway

Characteristic features;

• Every other carbon is converted to a C=O

• Allows nucleophilic attack by CoA-SH on remaining chain

• 1 CoA is used for every 2 carbon segment to release acetyl-CoA

• Each round produces

1 FADH₂ , 1 NADH, 1 Acetyl-CoA (2 in the last round)

Step 1: Dehydrogenation of Alkane to Alkene Catalyzed by isoforms of acyl-CoA dehydrogenase (AD) on the inner mitochondrial membrane

Step 2: Hydration of Alkene Catalyzed by two isoforms of enoyl-CoA hydratase:

Soluble short-chain hydratase (crotonase) Membrane-bound long-chain hydratase, part of trifunctional complex Water adds across the double bond yielding alcohol

Step 3: Dehydrogenation of Alcohol Catalyzed by β-hydroxyacyl-CoA dehydrogenase The enzyme uses NAD cofactor as the hydride acceptor Only L-isomers of hydroxyacyl CoA act as substrates Analogous to malate dehydrogenase reaction in the CAC.

Fig. 14 . The β- oxidation pathway

Step 4: Transfer of Fatty Acid Chain Catalyzed by acyl-CoA acetyltransferase (thiolase) via covalent mechanism, The carbonyl carbon in b -ketoacyl-CoA is electrophilic Active site thiolate acts as nucleophile and releases acetyl-CoA; Terminal sulfur in CoA-SH acts as nucleophile.

The fatty acid is now two carbons shorter and an Acetyl-CoA, has been generated which can be fed into the TCA cycle. The smaller fatty acid moves through the β-oxidation pathway again, producing another Acetyl-CoA and shrinking by 2 carbons.

By performing successive rounds of beta oxidation on a fatty acid, it is possible to convert it completely to Acetyl-CoA. Often fatty acids with odd numbers of carbons, the final reaction will yield acetyl-CoA and Coenzyme-A hooked to a three carbon fatty acid (propionyl-CoA). Propionyl-CoA is handled differently by different bacteria. In E. coli it is converted into pyruvate.

REFERENCES:

Text Books:

1. Jeffery C. Pommerville. Alcamo's Fundamentals of Microbiology (Tenth Edition). Jones and Bartlett Student edition.

2. Gerard J. Tortora, Berdell R. Funke, Christine L. Case. Pearson - Microbiology: An Introduction. Benjamin Cummings.

Reference Books:

1. Lansing M. Prescott, John P. Harley and Donald A. Klein. Microbiology. Mc Graw Hill companies.