Carbohydrates, branched-chain oxidation

The substantial progress made in synthesis of the complex carbohydrates occurring in medicinally important molecules68-72 is largely due to the discovery of new oxidative procedures that permit ready preparation of aldosuloses. Branched-chain sugars were obtained by nucleophilic additions to various lcetopentoses and ketohexoses subsequent condensation with purines and pyrimidines then afforded the desired natural, or synthetic, antibiotics (see, for example, Refs. 19 and 73). 

Thiamine pyrophosphate has two important coenzyme roles, both of which focus mostly on carbohydrate metabolism (Figs. 8.26 and 8.27). The active portion of the coen- rae is the thiazole ring. The first step in the oxidative decarboxylation of a-keto acids requires TPP. The two most common examples are pyruvate and a-ketoglutarate, oxidatively decarboxyatedto acetyl CoA and succinyl CoA, respectively. The same reaction is found in the metabolism of the branched-chain amino acids valine, isoleucine, leucine, and methionine. In all cases, TPP is a coenzyme in a mitochondrial multienzyme complex, consisting of TPP, lipoic acid, coenzyme A, FAD, and NAD. Note the number of vitamins required for the oxidative decarboxylation of a-keto acids thiamine (TPP), pantothenic acid (coenzyme A), riboflavin (FAD),and niacin (NAD). 

Because of the importance of carbonyl groups to the mechanism of condensation reactions, much of the assembly of either straight-chain or branched-carbon skeletons takes place between compounds in which the average oxidation state of the carbon atoms is similar to that in carbohydrates (or in formaldehyde, H2CO). The diversity of chemical reactions possible with compounds at this state of oxidation is a maximum, a fact that may explain why carbohydrates and closely related substances are major biosynthetic precursors and why the average state of oxidation of the carbon in... 

This stage is a stage of the forced chain branching (i.e. it leads to appearance on the new OH radical), which is an initiator of the chain process of carbohydrate oxidation. The macro-radical RO is usually less active and could cause the chain to break according to the reaction (6.12) with formation of the peroxide linkage ... 

An example of sensitive regulation at a branch point may be provided by the pathways of fatty acid utilization and oxidation in tissues. An increase in the extracellular long-chain fatty acid concentration results in many mammalian tissues in an increase in the rate of fatty acid oxidation. This is considered to be important in providing an alternative fuel for the tissue when the carbohydrate stores of the body are being depleted. Nonetheless the rate of fatty acid oxidation should also be controlled by the tissue in response to the demand for ATP this could be produced by... 

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