Coenzymes Biochemistry

Nemeria, N. S., Baykal, A., Ebenezer, J., Zhang, S., Yan, Y., Furey, W., Jordan, F. (2004). Tehtrahedral intermediates in thiamin diphosphate-dependent decarboxylations exist as a l, 4 -imino tautomeric form of the coenzyme, unlike the Michaelis complex or the free coenzyme. Biochemistry 43, 6565—6575. 

As is often the case, coenzyme biochemistry leads to unconventional organic chemistry. In this regard, coenzymes are nature s special reagents and their well-defined structures make them ideal molecules to use for developing the concept of structure-function relationship by bioorganic approaches (273). This chapter will thus be concerned with this aspect and special attention will be devoted to model design of coenzyme action. 

Krone UE, K Laufer, RH Thauer, HPC Hogenkamp (1989) Coenzyme F43Q as a possible catalyst for the reductive dehalogenation of chlorinated C-1 hydrocarbons in methanogenic bacteria. Biochemistry 28 10061-10065. 

Clark DD, JR Allen, SA Ensign (2000) Characterization of five catalytic activities associated with the NADPH 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate] oxidoreductase/carboxylase of the Xanthobacter strain Py2 epoxide carboxylase system. Biochemistry 39 1294-1304. 

Eall RR, ML Hector (1977) Acyl-coenzyme A carboxylases. Homologous 3-methylcrotonyl-CoA and geranyl-CoA carboxylases from Pseudomonas citronellis. Biochemistry 16 4000-4005. 

Nocek B, SB Jang, MS Jeong, DD Clark, SA Ensign, JW Peters (2002) Structural basis for COj fixation by a novel member of the disulfide oxidoreductase family of enzymes, 2-ketopropyl-coenzyme M oxidore-ductase/carboxylase. Biochemistry Al 12907-12913. 

Ohshiro, T. Kanbayashi, Y. Hine, Y., and Izumi, Y., Involvement of Flavin Coenzyme in Dibenzothiophene Degrading Enzyme-System from Rhodococcus-Erythropolis D-l. Bioscience Biotechnology and Biochemistry, 1995. 59(7) pp. 1349-1351. 

JEZ, J.M., FERRER, J.-L., BOWMAN, M.E., DIXON, R.A., NOEL, J.P., Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase, Biochemistry, 2000, 39, 890-902. 

In accordance with the recommendation of the Commission of the International Union of Biochemistry [R. H. S. Thompson, Classification and nomenclature of enzymes and coenzymes, Nature 193, 1227 (1902)] the terms NAD and NADP have been used instead of DPN and TPN, except in Fig. 4. The generic term nicotinamide nucleotides is used with the same significance as pyridine nucleotides. 

The design of fluorescent sensors is of major importance because of the high demand in analytical chemistry, clinical biochemistry, medicine, the environment, etc. Numerous chemical and biochemical analytes can be detected by fluorescence methods cations (H+, Li+, Na+, K+, Ca2+, Mg2+, Zn2+, Pb2+, Al3+, Cd2+, etc.), anions (halide ions, citrates, carboxylates, phosphates, ATP, etc.), neutral molecules (sugars, e.g. glucose, etc.) and gases (O2, CO2, NO, etc.). There is already a wide choice of fluorescent molecular sensors for particular applications and many of them are commercially available. However, there is still a need for sensors with improved selectivity and minimum perturbation of the microenvironment to be probed. Moreover, there is the potential for progress in the development of fluorescent sensors for biochemical analytes (amino acids, coenzymes, carbohydrates, nucleosides, nucleotides, etc.). 

Leloir, L.F. (1955). The uridine coenzymes. In Proceedings of the 3rd International Congress of Biochemistry. Liebecq, C., Ed.), pp. 154-162. Vaillant-Carmanne, Liege. 

Fisher, H. F., Adija, D. L., Cross, D. G. Dehydrogenase-reduced coenzyme difference spectra, their resolution and relationship to the stereospecificity of hydrogen transfer. Biochemistry 8, 4424—4430 (1969). 

S. Subramanian, J. B. A. Ross, L. Brand, and P. D. Ross, Investigation of the nature of enzyme-coenzyme interactions in binary and ternary complexes of liver alcohol dehydrogenase with coenzymes, coenzyme analogs, and substrate analogs by ultraviolet absorption and phosphorescence spectroscopy, Biochemistry 20, 4086-4093 (1981). 

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],... 

Fig. 18. Covalent substrate-coenzyme adducts in flavin biochemistry...

Garrett RH, Grisham CM (1995) Nicotinic acid and the nicotinamide coenzymes. In Biochemistry. Saunders, Orlando, p 468... 

So what does riboflavin do As such riboflavin does nothing. Like thiamine, riboflavin must undergo metabolic change to become effective as a coenzyme. It fact, it undergoes two reactions. The first converts riboflavin to riboflavin-5-phosphate (commonly known as flavin adenine mononucleotide, FMN), about which we will say no more, and the second converts it to flavin adenine dinucleotide, FAD. The flavins are a class of redox agents of very general importance in biochemistry. FAD is the oxidized form and FADH2 is the reduced form. ... 

Although the structures for molecules having niacin activity are simple, the forms in which they act in human biochemistry are not so simple. Nicotinic acid and nicotinamide are precursors for three complex coenzymes in multiple oxida-tion/reduction (redox) reactions nicotinamide mononucleotide, NMN nicotinamide adenine dinucleotide, NAD+ and nicotinamide adenine dinucleotide phosphate, NADP. I shall use NAD+ as representative of the class. NADH is the corresponding reduced form. ... 

Finally, we come to the last of the vitamins that appear on the contents list of my multivitamin pill—pantothenic acid. This water-soluble vitamin serves a single purpose in physiology and biochemistry it is a precursor to a far more complex molecule known as coenzyme A or, simply, CoASH. 

In this way, many biochemical systems can be linked together via a small number of pairs of compounds, with the fnnctions of X and Y, i.e. snch metabolic pairs play a major role in biochemistry. These compounds are known as coenzymes. Well-known examples include ADP/ATP, NAD+/NADH and NADF/NADPH. Such biochemical systems are discussed in Chapter 3. 

Nucleosides are also encountered in the structures of adenosine triphosphate (ATP) and coenzyme A (HSCoA). ATP provides nature with its currency unit for energy. Hydrolysis of ATP to adenosine diphosphate (ADP) liberates energy, which can be coupled to energy-requiring processes in biochemistry, and synthesis of ATP from ADP can be coupled to energy-releasing processes (see Box 7.25). 

Coenzyme A is used as the alcohol part of thioesters, which are more reactive than oxygen esters (see Section 7.9.3) and are thus exploited in biochemistry in a wide range of reactions, e.g. fatty acid biosynthesis and metabolism (see Section 15.5). 

C-Glycosides are typified by barbaloin, a component of the natural purgative drag cascara, but, as a group, the M-glycosides are perhaps the most important to biochemistry. Al-Glycosidic linkages are found in the nucleosides, components of DNA and RNA (see Section 14.1). In addition, nucleosides are essential parts of the structures of crucial biochemicals such as ATP, coenzyme A, NAD+, etc. The amine in these types of compound is part of a purine or pyrimidine base (see Section 14.1). 

Coenzyme A is another adenine nucleotide derivative, with its primary functional group, a thiol, some distance away from the nucleotide end of the molecule. This thiol plays an important role in biochemistry via its ability to form thioesters with suitable acyl compounds (see Box 7.18). We have seen how thioesters are considerably more reactive than oxygen esters, with particular attention being paid to their improved ability to form enolate anions, coupled with thiolates being excellent leaving groups (see Box 10.8). 

The next part presents the reactions involved in the interconversion of these compounds—the part of biochemistry that is commonly referred to as metabolism (pp. 88-195). The section starts with a discussion of the enzymes and coenzymes, and discusses the mechanisms of metabolic regulation and the so-called energy metabolism. After this, the central metabolic pathways are presented, once again arranged according to the class of metabolite (pp. 150-195). 

Leaver, M.J., Scott, K., George, S.G. (1993). Cloning and characterization of the major hepatic glutathione S-transferase from a marine teleost flatfish, the plaice Pleuronectes platessa), with structural similarities to plant, insect and mammalian theta-class coenzymes. Journal of Biochemistry, 292 189-195. 

D. M. Smith, S. D. Wetmore, and L. Radom, Theoretical Studies of Coenzyme-Bi2-Dependent Carbon-Skeleton Rearrangements, in Theoretical Biochemistry—Processes and Properties of Biological Systems, L. A. Ericksson, Ed., Elsevier, Amsterdam, The Netherlands, 2001, pp. 183-214. Electronic structure calculations are applied to the understanding and prediction of how enzymes can lower the barriers to the 1,2-shifts in radicals that occur in reactions catalyzed by B12. 

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

Wilson DK, Nakano T, Petrash JM, Quiocho FA. 1.7 A structure of FR-1, a fibroblast growth factor-induced member of the aldo-keto reductase family complexed with coenzyme and inhibitor. Biochemistry 1995 34 14323-14330. 

A review of the biochemistry of coenzyme B12 reactions, including the methylmalonyl-CoA mutase reaction. 

The vitamin biotin is formed in nature (left) by condensation of L-alanine with pimeloyl-CoAto form 8-amino-7-oxononanoate (AON). This compound is seen at the upper left of the center structure joined as a Schiff base with the coenzyme pyridoxal phosphate (PLP). This is a product complex of the enzyme AON synthase (see Webster et ah, Biochemistry 39,516-528,2000) Courtesy of D. Alexeev,... 

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