Enzyme-Based Organic Synthesis. Cheanyeh Cheng

acids to mitochondria for subsequent β‐oxidation. CrAT is homologous to other carnitine acyltransferases, particularly, to carnitine palmitoyltransferase 1 (CPT I) that serves the regulation of long‐chain fatty acid metabolism. Therefore, the reversibly catalyzed reaction between acetyl‐CoA and carnitine by CrAT makes CrAT a regulator for the cellular pool of CoA that, in turn, plays a role as a carrier of activated acetyl groups in the oxidation of energy metabolism substrates and in the synthesis of fatty acids and lipids. It is also known that the accumulation of fatty acyl‐CoAs in heart may induce apoptosis and inflammation and acetyl‐carnitine improves cognition in the brain [65–67].

Scheme 3.15 Protein acetylation with CRTase and DAMC without involving acetyl‐CoA.

      Source: Arora et al. [71].

The model acetoxy‐coumarins (AC), 7,8‐diacetoxy‐4‐methylcoumarin (DAMC), was shown to possess radical scavenger property by interacting with free radical to remove its acetyl group and give the acetyl cation (CH₃CO⁺) and the phenoxyl radical [68]. The antioxidant action of DAMC is independent on the formation of parent 7,8‐dihydroxy‐4‐methylcoumarin (DHMC). Calreticulin (CR) catalyzes the transfer of acetyl groups from AC to certain proteins [69, 70]; thus, CR was termed calreticulin transacetylase (CRTase). The enzymatic acetylation of protein by CRTase is unique and characterized as without involving acetyl‐CoA. CRTase of rat tracheal smooth muscle cells (TSMC) was characterized the specificity of DAMC for acetylating and activating nitric oxide synthase (NOS) as illustrated by Scheme 3.15 [71]. Since the activated TSMC NOS will enhance NO in airway cells, and NO is believed to ameliorate the exacerbation of airway diseases such as asthma and coronary obstructive pulmonary diseases (COPD), AC may be expected to find therapeutic applications in respiratory diseases [71, 72].

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