Phosphates covalent

In this reaction, phosphorylase a is converted to phosphorylase b by the cleavage of two serine phosphate covalent bonds, one on each subunit of glycogen phosphorylase. 

Nucleotides A nucleotide is base + sugar + phosphate covalently bonded together. In DNA, where the sugar is deoxyribose, this unit is a deoxynucleotide. 

Parenthetically, DNA is a fibrous sodium salt of double-stranded ribose-poly-phosphate covalently bonded to precise sequences of the four nucleotides adenine (A), thymine (T), glycine (G), and cytosine (C), with intemu-cleotide hydrogen bonds connecting the two strands, and which, in trios, form one bit of the genetic code. 

As outlined in Figure 3, the hydrolysis of paraoxon by human serum A-esterase(s) is very similar to the phosphorylation of B-esterases, such as acetylcholinesterase, by paraoxon. Both reactions involve an initial binding of paraoxon to the enzyme, followed by a rapid conformational change that produces diethyl phosphate and p-nitrophenol from paraoxon. p-Nitrophenol is quickly released from the enzyme, leaving diethyl phosphate covalently bound to enzyme. At this point, A-esterase quickly releases diethyl phosphate as a result of interacting with a water molecule. However, B-esterases, such as acetylcholinesterase, retain the diethyl phosphate for a much longer period of time, thereby resulting in inhibition of the enzyme. 

The last point frequently confuses students. However, it is just another way of saying that a nucleoside with a phosphate covalently attached to it is a nucleotide. Note also that it is redundant to refer to a nucleotide monophosphate - a nucleotide has at least one phosphate by definition. 

F. 393. Pyridoxal phosphate covalently attached to an amino acid substrate. The arrows indicate which bonds are broken for the various typies of reactions in which pyridoxal phosphate is involved. The X and Y represent leaving groups that may be present on the amino acid (such as the hydroxyl group on serine or threonine). 

R15 Phosphorus-31 NMR chemical shifts of phosphate covalently bound to proteins, Matheis, G, Whitaker, 3 R Int J Biochem 1984, 16, 867-873 (55 references)... 

P-NMR linewidths of phosphates covalently bound to the enzymes are governed by relaxation processes (dipolar interactions, anisotropic chemical shifts, and paramagnetic metal-ion effects, if any) and the correlation times associated with these processes. As discussed in Section II,A,1, noncova-lently bound substrates often exchange between different states, either on the enzyme or between the free and enzyme-bound states. The resultant lineshapes of P resonances of these substrate molecules depend on the spectral parameters and /), the linewidths in the different states in the absence of exchange, and the exchange rates between these states for the chosen set of experimental conditions. 

The tertiary metal phosphates are of the general formula MPO where M is B, Al, Ga, Fe, Mn, etc. The metal—oxygen bonds of these materials have considerable covalent character. The anhydrous salts are continuous three-dimensional networks analogous to the various polymorphic forms of siHca. Of limited commercial interest are the alurninum, boron, and iron phosphates. Boron phosphate [13308-51 -5] BPO, is produced by heating the reaction product of boric acid and phosphoric acid or by a dding H BO to H PO at room temperature, foUowed by crystallization from a solution containing >48% P205- Boron phosphate has limited use as a catalyst support, in ceramics, and in refractories. 

In contrast to monophosphates, starch phosphate diesters contain cross-links between two or more starch chains. This covalent linkage in the granule produces a starch product which swells less but is more resistant to heat, agitation, and acid than natural starch. 

It seems likely, therefore, that as the bound phosphate molecule is released, the cleft starts to open and the myosin head binds to actin (Figure 14.17d). Release of ADP coincides with a conformational change that fully opens the myosin cleft, causing actin to be tightly bound, and moves the lever arm to the "down" position. Since the myosin head is now strongly bound to actin at one end and covalently linked to the myosin fibril at the other... 

FIGURE 9.25 Teichoic acids are covalently linked to the peptidoglycan of Grampositive bacteria. These polymers of (a, b) glycerol phosphate or (c) ribitol phosphate are linked by phosphodiester bonds. 

Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues, 97.44 kD). Each subunit contains a pyridoxal phosphate cofactor, covalently linked as a Schiff base to Lys °. Each subunit contains an active site (at the center of the subunit) and an allosteric effector site near the subunit interface (Eigure 15.15). In addition, a regulatory phosphorylation site is located at Ser on each subunit. A glycogen-binding site on each subunit facilitates prior association of glycogen phosphorylase with its substrate and also exerts regulatory control on the enzymatic reaction. 

As shown in Figure 16.10, this reaction mechanism involves nucleophilic attack by —SH on the substrate glyceraldehyde-3-P to form a covalent acylcysteine (or hemithioaeetal) intermediate. Hydride transfer to NAD generates a thioester intermediate. Nucleophilic attack by phosphate yields the desired mixed carboxylic-phosphoric anhydride product, 1,3-bisphosphoglycerate. Several examples of covalent catalysis will be discussed in detail in later chapters. 

FIGURE 16.10 Formation of a covalent intermediate in the glyceraldehyde-3-phos-phate dehydrogenase reaction. Nucleophilic attack by a cysteine —SH group forms a covalent acylcysteine intermediate. Following hydride transfer to NAD, nucleophilic attack by phosphate yields the product, 1,3-bisphosphoglycerate. 

Definitive identification of lysine as the modified active-site residue has come from radioisotope-labeling studies. NaBH4 reduction of the aldolase Schiff base intermediate formed from C-labeled dihydroxyacetone-P yields an enzyme covalently labeled with C. Acid hydrolysis of the inactivated enzyme liberates a novel C-labeled amino acid, N -dihydroxypropyl-L-lysine. This is the product anticipated from reduction of the Schiff base formed between a lysine residue and the C-labeled dihydroxy-acetone-P. (The phosphate group is lost during acid hydrolysis of the inactivated enzyme.) The use of C labeling in a case such as this facilitates the separation and identification of the telltale amino acid. 

The mechanism of the first part of transamination is shown in Figure 29.14. The process begins with reaction between the a-amino acid and pyridoxal phosphate, which is covalently bonded to the aminotransferase by an iminc linkage between the side-chain -NTI2 group of a lysine residue and the PLP aldehyde group. Deprotonation/reprotonation of the PLP-amino acid imine in steps 2 and 3 effects tautomerization of the imine C=N bond, and hydrolysis of the tautomerized imine in step 4 gives an -keto acid plus pyridoxamine... 

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