Please answer the following question including the explanation of how you arrive
ID: 875370 • Letter: P
Question
Please answer the following question including the explanation of how you arrived to the answer. I asked this question earlier, and not all the questions I asked were answered, and explanations were not included.
A catabolic pathway exists for compound A, proceeding to compound F in 5 steps. Compound F proceeds through either an aerobic three step pathway to Compound I or a two step pathway to compound K. Compound F is a feedforward activator for the enzymes that catalyze the formation of both I and K. Compound G is a feedback inhibitor for the initial enzyme in the joint pathway and compound J is a feedback inhibitor for the enzyme that produces F.
a). Draw a diagram showing the regulation of this pathway.
b). If ATP is involved in regulation of this pathway, should it be an inhibitor or an activator? Why?
c). Where should the regulation in b) take place? Why?
Explanation / Answer
Thermally upward evolution (e.g., from mesophiles to hyperthermophiles) would require mutations for all thermally relevant features, notably for increasing the stability of all folding structures. Now, any such mutation has selective value in a thermally challenging environment, if and only if it strengthens the thermally most challenged feature, i.e., the thermally least stable structure. This means that all features would have to adapt thermally upwards in a specific order. Moreover, all thermal adaptations of whole organisms are restricted to small temperature increments, as evidenced by the typical thermal growth curve of bacteria with a gradual rise from the minimum growth temperature to optimum growth temperature and a steep drop between the optimum growth temperature and the maximum growth temperature. Thus, thermally upward adaptation of whole organisms could occur only at an extremely low rate, which renders it probabilistically forbidden. Thermally downward evolution by contrast proceeds by haphazard losses of thermal features, notably structural stabilizers, which do not have to occur in a specific order, nor by tiny increments.
(2)
Some protein folding structures are stabilized by sets of ligators (e.g., pairs of C-X-X-C) that form strong coordination bonds to transition metal centers (e.g., Fe2+, Zn2+). For thermally upward adaptation by the emergence of such cross-linking the set of ligators would have to be installed simultaneously by sequence covariation, which is improbable. In thermally downward evolution, however, losses of ligators may occur haphazardly, one-by-one. This explains why some proteins (e.g., aminoacyl synthetases and ribosomal proteins) show on average a decrease, but never an increase, of the number of C-X-X-C signatures in the direction from hyperthermophiles to psychrophiles [33,34]. Such signatures are sometimes maintained in mesophiles as molecular relics or, when lost recently, e.g., by single cysteine removal, they may reappear as molecular atavisms.
(3)
Kinetic experiments show that in the presence of an enzyme a biochemical reaction requiring enthalpic catalysis shows typically a gentle drop of reaction rate with decreasing temperature. When such reaction is carried out in the absence of an enzyme the rate decrease with decreasing temperature is extremely steep, and steepness correlates with the sluggishness of the reaction. At the temperature of mesophiles the non-catalyzed reaction rate is so extremely low that early catalysts with low catalytic activity could not have increased the reaction rate to a metabolically useful level [35,36]. The conclusion is inescapable for multi-step metabolic pathways: Only at temperatures typical for hyperthermophiles (or above) would rates of all involved uncatalyzed reactions be high enough to be readily augmented to metabolically required rates by modest catalytic innovations. Thus, the evolution of catalysts for metabolic pathways could only have started at high temperatures, and subsequent thermally downward evolution of enzymatic catalysts would automatically generate metabolic rates much higher by many orders of magnitude than corresponding rates in a mesophilic origin of life. The fact that some uncatalyzed reactions are relatively fast at low temperatures is here of no concern, because a pathway of reactions is as slow as its slowest step. The hyperthermophilic requirement of early life must have persisted as long as the catalytic activities of the evolving catalysts remained relatively low. In any event, all biochemical reactions, whose non-enzymatic parent reactions face a very high catalytic burden, must have entered the metabolism in the all-hyperthermophilic phase of early life. An evolution to lower and lower temperatures became possible to the extent that catalysts evolved to acquire higher and higher catalytic activity, and this evolution was possible, because the initial catalytic burden was not too high. With the appearance of the genetic machinery essentially all metabolic reactions came under enzymatic control and this enabled an evolution to mesophilic and psychrophilic lifestyles. Thermal rate leveling at the origin of life was thus replaced by adaptational rate leveling (Wolfenden theorem I).