Adenine nucleotides functions

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). 

A variety of enzyme cofactors serving a wide range of chemical functions include adenosine as part of their structure (Fig. 8-41). They are unrelated structurally except for the presence of adenosine. In none of these cofactors does the adenosine portion participate directly in the primary function, but removal of adenosine generally results in a drastic reduction of cofactor activities. For example, removal of the adenine nucleotide (3 -phosphoadenosine diphosphate) from acetoacetyl-... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Fig. 5. Steady-state cytosolic adenine nucleotide concentrations. Plot of equations (10)-(14) as a function of the degree of coupling in the interval qe(0.9,l). Values of the parameters AGj hos = 8.5 kcal/mole, AGak = 0.15 kcal/mole, Pj = 0.008 M, Xa = 50 kcal/mole, Z = 3, 0 = l. Inserted points experimental values from perfused livers.5 Normalized plots with 2=1.

A mitochondrial T3-binding protein has been detected [11] but its function and physiological relevance remain largely unknown. Recently, it has been shown that a mitochondrial enzyme, adenine nucleotide transferase, exhibits high affinity binding of T3 [12]. 

Answer Within organelles, reaction intermediates and enzymes can be maintained at different levels from those in the cytosol and in other organelles. For example, the ATP/ADP ratio is lower in mitochondria than in the cytosol because the role of adenine nucleotides in the mitochondrial matrix is to accept a phosphoryl group, whereas the role in the cytosol is to donate a phosphoryl group. Similarly, different NADH/NAD+ and NADPH/NADP+ ratios reflect the reductive (biosynthetic) functions of the cytosol and the oxidative (catabolic) functions of the mitochondrial matrix. By segregating reaction sequences that share intermediates, the cell can regulate catabolic and anabolic processes separately. 

The mitochondrial permeability transition (MPT) is the loss of the inner mitochondrial membrane impermeability to solutes caused by opening of the MPT pore (MPTP). In turn, this action results in a loss of mitochondrial function and provides a common mechanism implicated in activation of mi-tophagy/autophagy, apoptosis, and necrosis in different cell systems. Although the composition of MPTP is not fully settled, multiple studies suggest involvement of adenine nucleotide translocase (ANT) in the inner mitochondrial membrane, voltage-dependent anion channel (VDAC or porin) in the outer membrane, and cyclophilin D (CypD) in the matrix. 

The major function of oxidative phosphorylation is to generate ATP from ADP. However, ATP and ADP do not diffuse freely across the inner mitochondrial membrane. How are these highly charged molecules moved across the inner membrane into the cytosol A specific transport ATP-ADP translocase (also called adenine nucleotide... 

Not all the transporters discussed above are present in aU types of mitochondria the set of activities present in mitochondria depends on the functional needs of the cells from which the mitochondria are isolated. The adenine nucleotide and phosphate transporters are present in all mitochondria thus far studied. This reflects the fact that the major function of mitochondria is the synthesis of ATP. Even in the rare instances (e.g., brown fat mitochondria [55] and mitochondria in anaerobically growing yeast [56]) where the major function is not ATP synthesis, mitochondria normally have active adenine nucleotide transport. The pyruvate transporter also appears to be ubiquitous. The carnitine transporter has been studied in liver [57], heart [35] and sperm [58] and is probably present in all mitochondria which use long-chain fatty acids. 

Adenosine, a natural purine metabolite of adenine nucleotides, is a key regulator of many physiologic functions including vascular blood flow, platelet thrombotic... 

Nees, S and Gerlach, E, Adenine nucleotide and adenosine metabolism in cultured coronary endothelial cells. In Regulatory functions of adenosine, (eds. Berne, RM, Rail, TW and Rubio, R), Martinus Nijhoff Publishers, The Hague, 1983,347-360. 

Agarwal, KC, Modulation of platelet functions by plasma adenosine. In Role of adenosine and adenine nucleotides in the biological system (eds Imai, S and Nakazawa, M), Elsevier Science Publishers, Amsterdam, 1991,457-468. 

Adenylate kinase, which is abundant in muscle as in many other tissues, decreases in dystrophic mouse and human muscle (H6, P7). This enzyme, by interconverting adenine nucleotides, probably functions in the control of glycolysis it seems reasonable to suppose, therefore, that its activity may be governed by the same factors which influence glycolytic enzymes, as discussed above. A severe decline in the activity of AMP deaminase occurs in muscular dystrophy (P6, P7) and also in denervated muscle (M12) and in some cases of muscle affected by hypokalemic periodic paralysis (E6). Skeletal muscle normally contains a higher concentration of this enzyme than other tissues in fact, it is almost absent from some, such as liver. Its physiological function, and hence the significance of the sharp decline in its activity in diseased muscle, is still a matter of speculation. 

Liver is the principal site of D-fructose metabolism. D-Fructose is transported to the liver from the small intestine by way of the portal blood-vessel. Experiments with perfused pig and rat livers revealed that the rate of elimination of D-fructose from blood is a function of the sugar concentration,26,27 and follows Michaelis-Menten kinetics.27,28 Carrier-mediated, liver-membrane transport of D-fructose has a high29 Km and Vmax, in comparison to the intracellular phosphorylation constants of D-fructose in both pigeon and rat livers.27,28 For example, the calculated rat-liver transport for D-fructose has a Km of 67 mM and a Vmax of 30 /u,mole.min. g-1, in contrast to the lower, calculated fruc-tokinase Km of 1.0 mM and Vmax of 10.3 pmole. min r1. g 1 with D-fruc-tose and Km of 0.54 mM with adenosine 5 -triphosphate (ATP). In perfused pig-liver,28 the transport Km for D-fructose is only ten times that of intracellular phosphorylation by fructokinase. Hence, D-fructose-transport values suggested that, at physiological D-fructose concentrations, membrane transport limits the rate of uptake, thereby protecting the liver from severe depletion of adenine nucleotide.28,29... 

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