Long chain enzyme-catalyzed

All of the other enzymes of the /3-oxidation pathway are located in the mitochondrial matrix. Short-chain fatty acids, as already mentioned, are transported into the matrix as free acids and form the acyl-CoA derivatives there. However, long-chain fatty acyl-CoA derivatives cannot be transported into the matrix directly. These long-chain derivatives must first be converted to acylearnitine derivatives, as shown in Figure 24.9. Carnitine acyltransferase I, located on the outer side of the inner mitochondrial membrane, catalyzes the formation of... 

The biochemical mechanism of bacterial luminescence has been studied in detail and reviewed by several authors (Hastings and Nealson, 1977 Ziegler and Baldwin, 1981 Lee et al., 1991 Baldwin and Ziegler, 1992 Tu and Mager, 1995). Bacterial luciferase catalyzes the oxidation of a long-chain aldehyde and FMNH2 with molecular oxygen, thus the enzyme can be viewed as a mixed function oxidase. The main steps of the luciferase-catalyzed luminescence are shown in Fig. 2.1. Many details of this scheme have been experimentally confirmed. 

Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ...

Transition-metal- and enzyme-catalyzed alkylations of ammonia and amines with alcohols and diols have been reviewed59. RuCl2(PPh3)3 is a homogeneous catalyst for the reaction of long-chain terminal alcohols with secondary amines to give tertiary amines (equation 22)60. 

Thiolester hydrolases (EC 3.1.2) play an important role in the biochemistry of lipids. They catalyze the hydrolysis of acyl-coenzyme A thiolesters of various chain lengths to free fatty acids and coenzyme A. The current list of over 20 specific enzymes includes acetyl-CoA hydrolase (EC 3.1.2.1), pal-mi toy 1-Co A hydrolase (EC 3.1.2.2), and an acyl-CoA hydrolase (EC 3.1.2.20) of broad specificity for medium- to long-chain acyl-CoA [128],... 

This enzyme [EC 2.3.1.76], also referred to as retinol fatty-acyltransferase, catalyzes the reaction of an acyl-CoA derivative with retinol to generate coenzyme A and the retinyl ester. The CoA derivative can be palmi-toyl-CoA or other long-chain fatty-acyl derivatives of coenzyme A. 

This enzyme [EC 2.5.1.26], also known as alkylglycerone-phosphate synthase, catalyzes the reaction of 1-acylglyc-erone 3-phosphate with a long-chain alcohol to produce 1-alkylglycerone 3-phosphate and a long-chain acid anion. In this reaction, the ester-hnked fatty acid of the substrate is removed and replaced with a long-chain alcohol in an ether hnkage. 

This enzyme [EC 6.2.1.15], also known as arachido-nateiCoA ligase, catalyzes the reaction of arachidonate with ATP and coenzyme A to generate arachidonyl-CoA, AMP, and pyrophosphate (or, diphosphate). The enzyme can also use 8,11,14-icosatrienoate as a substrate, but not the other long-chain fatty acids. It should be noted that this enzyme is not identical to long-chain acyl-CoA synthetase [EC 6.2.1.3]. 

This enzyme [EC 3.1.1.13] (also known as cholesterol esterase, sterol esterase, cholesterol ester synthase, and triterpenol esterase) catalyzes the hydrolysis of a steryl ester to produce a sterol and a fatty acid anion. This class represents a group of enzymes exhibiting broad specificity. They act on esters of sterols and long-chain fatty acids, and may also bring about the esterification of sterols. These enzymes are typically activated by bile salts. See also Esterases D. P. Hajjar (1994) Adv. Enzymol. 69, 45. 

This enzyme complex [EC 2.3.1.85] catalyzes the conversion of acetyl-CoA, n moles malonyl-CoA, and 2n moles of NADPH to yield long-chain fatty acids, plus (n+1)... 

This FMN-dependent enzyme [EC 1.1.3.15], also known as (5)-2-hydroxy-acid oxidase, catalyzes the reaction of a (5)-2-hydroxy acid with dioxygen to produce a 2-oxo acid and hydrogen peroxide. The enzyme exists as two major isoenzymes. The A form of the protein preferentially oxidizes short-chain aliphatic hydroxy acids. The B form preferentially oxidizes long-chain and aromatic hydroxy acids. The rat isoenzyme B form also acts as an L-amino-acid oxidase. 

This enzyme [EC 1.1.1.35] catalyzes the reaction of an (5)-3-hydroxyacyl-CoA with NAD+ to produce a 3-oxo-acyl-CoA and NADH. The enzyme will also utilize 5-3-hydroxyacyl-A-acylthioethanolamine and 5-3-hydroxya-cylhydrolipoate as substrates. The enzyme isolated from some sources can also utilize NADP+ as the coenzyme, albeit as a weaker substrate. In addition, there is a broad specificity with respect to the acyl chain length (note that there is a long-chain-length 3-hydroxyacyl-CoA de-hydogenase [EC 1.1.1.211]). 

This enzyme [EC 1.3.99.13] catalyzes the reaction of a long-chain acyl-CoA with an electron-transferring fla-voprotein to produce a 2,3-dehydroacyl-CoA and the reduced electron-transferring flavoprotein. 

This enzyme [EC 1.2.1.48] catalyzes the reaction of a long-chain aldehyde with NAD to produce a long-chain acid anion and NADH. The best substrate is reported to be dodecylaldehyde. 

This enzyme [EC 3.1.1.23], also known as monoacylglyc-erol lipase, catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids. See also Lipases... 

This enzyme [EC 1.1.1.73] will catalyze the reaction of 1-octanol with NAD+ to produce 1-octanal and NADH. The enzyme can act on other long-chain alcohols, albeit not as effectively. 

Resolution of branched alkanoic adds. Hydrolase-catalyzed esterification of 2-methylalkanoic acids can be fairly efficient, especially for acids with long chains, provided that the conditions are carefully adjusted by immobilization of the enzyme (in some cases), by control of the water activity, and by proper choice of the appropriate alcohol as nucleophile as well as the correct solvent [134]. The alcohol concentration does also influence the E-value [133]. It is important to note that the esterifications are reversible, thus preventing easy access to the remaining substrate in high ees. Some representative examples are given in Table 4.4. A procedure based on iterative resolutions can be used to provide both enantiomers of 2-methyloctanoic acid in high ees (>99%) and reasonable yields (25% for S- and 43% for R-acid based on the starting racemic acid) [137]. 

The PDH complex of mammals is strongly inhibited by ATP and by acetyl-CoA and NADH, the products of the reaction catalyzed by the complex (Fig. 16-18). The allosteric inhibition of pyruvate oxidation is greatly enhanced when long-chain fatty acids are available. AMP, CoA, and NAD+, all of which accumulate when too little acetate flows into the citric acid cycle, allosterically activate the PDH complex. Thus, this enzyme activity is turned off when ample fuel is available in the form... 

The regulated step in fatty acid synthesis (acetyl CoA - malonyl CoA) is catalyzed by acetyl CoA carboxylase, which requires biotin. Citrate is the allosteric activator, and long-chain fatty acyl CoA is the inhibitor. The enzyme can also be activated in the presence of insulin and inactivated in the presence of epinephrine or glucagon. 

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