Biochemistry - The Chemical Reactions of Living Cells Volume 2 - D. Metzler 1980

Types of reactions catalyzed by enzymes
Brief overview of some metabolic pathways
Initiating reaction or activation of metabolites

The primary function of the most active metabolic pathways is to provide The Cell with ATP and other high-energy (i.e., "energy-rich") intermediates that can be utilized in biosynthetic processes and other energy-requiring transformations. Therefore, we should first examine those metabolic pathways that effect the Catabolism of food molecules and couple it to the synthesis of ATP.

Once a polymeric nutrient has been digested (hydrolyzed) and the resulting monomeric products have entered the cell, an initial energy-requiring reaction is usually necessary. For example, the Hydrolysis of fats (whether occurring in the intestinal lumen or intracellularly) yields free Fatty acids. Before fatty acids can participate in further metabolic transformations, they are attached to a specialized coenzyme, coenzyme A (CoA), forming a fatty acyl-CoA derivative. This reaction requires the expenditure of ATP, specifically the hydrolysis of ATP to AMP and PP_i (Supplement 3-A). Similarly, upon entering Cells, glucose is converted into a phosphoric acid ester—glucose-6-phosphate. The reaction forming glucose-6-phosphate also requires the input of ATP. Major Metabolic Pathways frequently begin with one of these two compounds: a fatty acyl-CoA derivative or glucose-6-phosphate. The structural formulas for these compounds are shown at the top of Fig. 7-1.

Supplement 7-A

Arsenic

Arsenate, AsO^3-₄, is analogous to phosphate in its chemical properties, such as molecular size, Structure, and ability to participate in biochemical reactions. However, arsenic acid esters possess a much lower stability than phosphoric acid esters. If they are formed On the surface of an enzyme, they undergo immediate hydrolysis upon dissociation from the enzyme. This property largely explains the toxicity of arsenic acid compounds.

Arsenate can substitute for phosphate in all phosphorolytic reactions—for example, in The breakdown of Glycogen catalyzed by Glycogen phosphorylase and the Cleavage of sucrose catalyzed by sucrose phosphorylase (Sec. 3.6). In both cases, glucose-1-arsenate appears to be formed as an intermediate, which, however, rapidly hydrolyzes to release free glucose. This overall process is termed arsenolysis. Another reaction in which arsenate can replace phosphate is The oxidation of glyceraldehyde-3-phosphate in the presence of P_i to yield 1,3-diphosphoglycerate:

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The subsequent transfer of the 1-phosphate group to ADP is a crucial energy-yielding step in overall METABOLISM (Chap. 8, Sec. 3.5). When arsenate is used instead of phosphate, the resulting acyl arsenate (1-arseno-3-phosphoglycerate) hydrolyzes to yield 3-phosphoglycerate. Thus, in the presence of arsenate, the oxidation of glyceraldehyde-3-phosphate does not stop, but the synthesis of ATP no longer occurs. In other words, arsenate uncouples phosphorylation from oxidation. Arsenate can partially replace phosphate in stimulating mitochondrial Respiration while uncoupling Oxidative Phosphorylation (Chap. 10, Sec. D.5).

Enzymes that normally act on a phosphorylated substrate will generally catalyze the slow Conversion of the corresponding nonphosphorylated substrate in the presence of arsenate. This reaction presumably becomes possible because a short-lived arsenate ester of the substrate is formed on the enzyme surface.

Arsenite is notorious for reacting vigorously with thiol groups, particularly dithiols such as Lipoic Acid:

By blocking lipoic acid-dependent oxidative enzymes (Chap. 8, Sec. K), arsenite promotes the accumulation of Pyruvate and other α-keto acids.

Although arsenic compounds have been used in medicine for over 2,000 years, it was only in our century that certain arsenic derivatives began to be utilized for drug development. For instance, in 1905 it was discovered that sodium arsanilate is toxic to trypanosomes, and Ehrlich's successful use of arsenic compounds to treat Syphilis (in 1909) first drew widespread attention to the field of Chemotherapy for bacterial infections.