Reaction with ATP

In fatty-acid biosynthesis, a carboxylic acid is activated by reaction with ATP to give an acyl adenylate, which undergoes nucleophilic acyi substitution with the — SH group or coenzyme A. (ATP = adenosine triphosphate AMP = adenosine monophosphate.)... 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

O Glucose is phosphorylated by reaction with ATP to yield glucose 6-phosphate. 

Step 3 of Figure 29.7 Phosphorylation Fructose 6-phosphate is converted in step 3 to fructose 1,6-bisphosphate (FBP) by a phosphofmctokinase-catalyzed reaction with ATP (recall that the prefix bis- means two). The mechanism is similar to that in step 1, with Mg2+ ion again required as cofactor. Interestingly, the product of step 2 is the tv anomer of fructose 6-phosphate, but it is the (3 anomer that is phos-phorylated in step 3, implying that the two anomers equilibrate rapidly through the open-chain form. The result of step 3 is a molecule ready to be split into the two three-carbon intermediates that will ultimately become two molecules of pyruvate. 

Koenigs-Knorr reaction of, 990 molecular model of, 119, 126, 985 mutarotation of, 985-986 pentnacetyl ester of, 988 pentamethyl ether of, 988 pyranose form of, 984-985 pyruvate from. 1143-1150 reaction with acetic anhydride, 988 reaction with ATP, 1129 reaction with iodomethane, 988 sweetness of. 1005 Williamson ether synthesis with. 988... 

These P-, V0Vr and ABC-superfamily members all catalyze reactions with ATP that drive conformational cycles to move substrates across membranes and uphill to higher concentrations. 

Many nonsteroidal anti-inflammatory drugs (NSAIDs) are substituted 2-arylpropionic acids. Most NSAIDs also have a chiral carbon next to the carboxylate and are administered as a racemic mixture of the two enantiomers. In general, the (S)-enantiomcr is responsible for most of the antiinflammatory activity of these agents. It was found that the (/ -enantiomer is converted to the (S)-enantiomer but the reverse does not occur (23). As with amino acid conjugation, the pathway involves reaction with ATP to form an AMP ester, which is, in turn, converted to a Co-A ester, and it is the Co-A ester that undergoes chiral inversion (Fig. 7.14). Substrates include ibuprofen, naproxen, and fenoprofen. 

CMP, <3> reaction with ATP, enzyme from Novikoff ascites hepatoma [3]) [3]... 

MECHANISM FIGURE 16-16 The role of biotin in the reaction catalyzed by pyruvate carboxylase. Biotin is attached to the enzyme through an amide bond with the e-amino group of a Lys residue, forming biotinyl-enzyme. Biotin-mediated carboxylation reactions occur in two phases, generally catalyzed by separate active sites on the enzyme as exemplified by the pyruvate carboxylase reaction. In the first phase (steps to ), bicarbonate is converted to the more activated C02, and then used to carboxylate biotin. The bicarbonate is first activated by reaction with ATP to form carboxyphosphate (step ), which breaks down to carbon dioxide (step ). In effect, the... 

The carboxyl groups of the amino acids are converted to reactive acyl adenylates by reaction with ATP, just as in Eq. 10-1. Each "activated" amino acid is carried on a molecule of transfer RNA (tRNA) and is placed in the reactive site of a ribosome when the appropriate codon of the mRNA has moved into the site. The growing peptide chain is then transferred by a displacement reaction onto the amino group of the activated amino acid that is being added to the peptide chain. In this manner, new amino acids are added one at a time to the carboxyl end of the chain, which always remains attached to a tRNA molecule. The process continues until a stop signal in the mRNA ends the process and the completed protein chain is released from the ribosome. Details are given in Chapter 29. 

The active site of a type II synthetase is shown in Fig. 29-9C,D.217/217a The expected movement of electrons in the reaction with ATP is illustrated by the green arrow in D. Both metal ions and active-site protein groups may participate as is also proposed for another type II enzyme.229... 

In both schemes, the upper pathway represents the formation of an unstable intermediate that is then trapped by reaction with ATP. By contrast, the lower pathways represent activation of a carbonyl group by ATP, followed by loss of a proton (to form enol pyruvate eq. 9) or reaction with ammonia (to yield an intermediate for the formation of CTP eq. 10). ATP has long been known to drive metabolic processes if it phosphorylates carbonyl groups, it will prove to serve a catalytic role as well. 

We can also get some information by comparing the modern biosynthetic pathways to the capabilities of prebiotic chemistry. Amino acids are usually activated in living organisms by reaction with ATP both through the ribosomal and non-ribosomal peptide synthesis pathways. Amino acyl fRNA synthetases bind ATP and free amino acids to cause the highly unfavorable adenylate anhydride formation to be close to equilibrium in the active site. 

T3i metabcJic breakdown of triacylglyceroJs bt ns with their hydrelyjis ia the stomach and small intestine to yiold glycerol plus fatty adds. Cl>verot is first phoopho-rylated by reaction with ATP and is thm oxidised to yield ycenildeh e 3 phosphate. which enters the carbohydrate catabolic path way. (Well scuss this in detail in Section 2. 3.)... 

Phosphorylation of the carboxyl group by reaction with ATP yields 1,3-bisphospho-glycerate. 

In the cell s Golgi apparatus it can be converted to sulfate polysaccharides. Alternatively, further reactions with ATP can lead to PAPS which can then be reduced to sulhde through sulhte using a molybdenum in the initial step and then a haem/ Fe S sulhte reductase (Frausto da Silva and Williams, 2001). 

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