Coenzyme synthesis

In this hereditary disease up to 1 - 2 g of methylmalonic acid per day (compared to a normal of <5 mg/day) is excreted in the urine, and a high level of the compound is present in blood. Two causes of the rare disease are known/ One is the lack of functional vitamin B12-containing coenzyme. This can be a result of a mutation in any one of several different genes involved in the synthesis and transport of the cobalamin coenzyme.6 Cultured fibroblasts from patients with this form of the disease contain a very low level of the vitamin B12 coenzyme (Chapter 16), and addition of excess vitamin B12 to the diet may restore coenzyme synthesis to normal. Among elderly patients a smaller increase in methylmalonic acid excretion is a good indicator of vitamin B12 deficiency. A second form of the disease, which does not respond to vitamin B12, arises from a defect in the methylmalonyl mutase protein. Methylmalonic aciduria is often a very severe disease, frequently resulting in death in infancy. Surprisingly, some children with the condition are healthy and develop normally.3 1... 

Pteridine enzymes and coenzymes, synthesis and biological role of 8OMI32. Pteridine N-oxides 74KGS1299. 

Because most vitamins function as coenzymes, the symptoms of vitamin deficiencies reflect the loss of specific enzyme activities dependent on the coenzyme form of the vitamin. Thus, drugs and toxins that inhibit proteins required for coenzyme synthesis (e.g., vitamin transport proteins or biosynthetic enzymes) can cause the symptoms of a vitamin deficiency. This type of deficiency is called a functional deficiency, whereas an inadequate intake is called a dietary deficiency. 

The conversion of nicotinamide to nicotinic acid requires the activities of a deaminase and a ribonucleotide pyrophosphorylase. Although a detailed description of mechanisms controlling NAD coenzyme synthesis in mammalian tissues is not available, it has been suggested that the regulatory restraints are... 

A considerable advance in elaborating the pathway of pyridine coenzyme synthesis resulted from the contributions of Preiss and Handler (118, 1B6-1B8). Before discussing the experiments of these investigators, it may be of value to review some of the earlier work on the metabolism of nicotinic acid and nicotinamide in erythrocytes. It has been known for some time that nicotinic acid taken orally results in a significant increase in the pyridine nucleotide content of human red blood cells (1B9, ISO). When equal concentrations of nicotinamide were given under identical conditions, there was no effect on the erythrocyte DPN level. Isolated erythrocytes have also been found to show a rise in DPN when incubated with nicotinic acid and not with nicotinamide. However, incubation with nicotinamide leads to a marked accumulation of nicotinamide mononucleotide (ISl). In this connection, it is of importance to point out that the level of the DPN pyrophosphorylase is extremely low in the red blood cell (ISB). 

In the earliest period of complex natural product synthesis, from Robinson s 1917 tropinone synthesis to Eschenmoser and Woodward s 1973 coenzyme synthesis, metal-catalyzed reactions played no great role. In contrast, modern organic syntheses often involve numerous transition metal-catalyzed steps. Main-group compounds, such as BuLi, MeMgBr, or NaBH4, tend to act in stoichiometric quantity as reagents, while the more expensive transition metals, typically complexes of Pd, Rh, or Ru, tend to be used as catalysts and therefore in much lower amounts, for example, 0.1-5 mol% (mmol catalyst per 100 mmol substrate). 

A. Synthesis and Degradation of Vitamins. B. Phosphorylation of Vitamins. C. Coenzyme Synthesis and Breakdown. 

A further point indicates the need to follow coenzyme synthesis in the... 

Roseman, S., Distler, J. J., Moffatt, J. G., and Khorana, H. G., 1961a, Nucleoside polyphosphates. XI. An improved general method for the synthesis of nucleotide coenzymes. Synthesis of uridine-5, cytidine-5, and guanosine-5 diphosphate derivatives, 7. Am. Chem. Soc. 83 659-663. 

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