Histidine energy charge

The PR-ATP synthetase is inhibited by ADP and AMP as well as by histidine. The inhibitory effects of ADP and AMP on the PR-ATP synthetase have made it one of the premier examples of Atkinson s energy charge theory [22, 23, and Atkinson, this volume]. Brieffy, the theory proposes that the relative concentrations of the three adenylates — ATP, ADP, and AMP— regulate metabolism within the cell. A low... 

Feedback inhibition of the first enzyme in the pathway keeps the pathway adjusted to the availabihty of external histidine. When sufficient exogenous histidine is present, feedback inhibition completely stops the biosynthesis of histidine. Inhibition of the first enzyme by ADP and AMP adjusts the pathway to the energy charge status of the cell. Together, these repression and inhibition controls provide a complex circuitry by which the rate of histidine biosynthesis is correlated with the cell s needs and potential. 

The carbonic anhydrase (Cam) in M. thermophila cells is elevated several fold when the energy source is shifted to acetate, suggesting a role for this enzyme in the acetate-fermentation pathway. It is proposed that Cam functions outside the cell membrane to convert CO2 to a charged species (reaction A4) thereby facilitating removal of product from the cytoplasm. Cam is the prototype of a new class (y) of carbonic anhydrases, independently evolved from the other two classes (a and P). The crystal structure of Cam reveals a novel left-handed parallel P-helix fold (Kisker et al. 1996). Apart from the histidines ligating zinc, the activesite residues of Cam have no recognizable analogs in the active sites of the a- and P-classes. Kinetic analyses establish that the enzyme has a zinc-hydroxide mechanism similar to that of Cab (Alber et al. 1999). 

Let us consider the mechanism of glyceraldehyde 3-phosphate dehydrogenase in detail (Figure 16.8). In step 1, the aldehyde substrate reacts with the sulfhydryl group of cysteine 149 on the enzyme to form a hemithioacetal. Step 2 is the transfer of a hydride ion to a molecule of NAD + that is tightly bound to the enzyme and is adjacent to the cysteine residue. This reaction is favored by the deprotonation of the hemithioacetal by histidine 176. The products of this reaction are the reduced coenzyme NADH and a thioester intermediate. This thioester intermediate has a free energy close to that of the reactants. In step 3, orthophosphate attacks the thioester to form 1,3-BPG and free the cysteine residue. This displacement occurs only after the NADH formed from the aldehyde oxidation has left the enzyme and been replaced by a second NAD+. The positive charge on the NAD+ may help polarize the thioester intermediate to facilitate the attack by orthophosphate. 

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