Question

1. Aconitase is an enzyme that displays moonlighting behavior dependent on cytosolic [iron]. When the concentration of iron is low, aconitase undergoes a shift towards mRNA binding activities. Please speculate as to the structural basis for this [iron]-dependent activity switch. What is the role and function of the iron-sulfur cluster in aconitase? What is the physiologic relevance of aconistase’s functional dependence on [iron]?
2. What is necessary in an enzyme’s active site in order for a symmetric molecule to react asymmetrically with the enzyme? Please provide an example of this phenomenon using an enzyme from the citric acid cycle.
3. Metabolic functions must occur with high efficiency to insure continued survival of the organism. Why is a process as complex as the citric acid cycle actually an economical way for cells to do their metabolic business? How does the citric acid cycle interact with other pathways that we have talked about in this class? Do such overlaps between the citric acid cycle and other pathways enhance or hinder overall metabolic efficiency?

Answer 1

LOL een ** Aconitase is an iron-sulfer protein and id a malen a major enzyme of the TCA cycle that Falyzes the conversation of citrate to toate under dronnich conditions, In Escherichia coli, aconitase B C AcnB) is a typical moonlighting protien that can Switch to its apo formi Capo-AmB] which favors binding its own MARNA S'UTR and ? stabilize it when intrecelular from kron become score. The small regualstory RNA CSRANA) RynB has previously been shown to promote RNaseta department : degradition of acn B MRNA when it was expressed from an cetopie arabinore - department promológ, indeperty of Intro- celluler iron level. . In marked contrast, we report here that expression of Ry hb under low-inon conditions did not result in acnB mRNA degradation even when Ryhis was bound to aim B ribosome binding site (RBS). Genetic and biochemical evidence suggested cs that he ander low-inon conditions, apor. CamScanner

Am B bound a Roase E degradation, where as RyR13 1 B was IB bound to an B S'UPR close to anase e clearage site site that is sential for RynB - Indeed amb ARNA ation, where as Rynis can block QmB translation ispitation, RNase. e department degradation of prevented boy apot AcnB binding close to the cte avage site. This previouly un- characterized regula regulation suggesteds an intricate post- transcriptional mechanis at prepresses protein expression while insuring mRNA slability. e To catalyze reaction, a enzyme will grab on (bindz to one or more reactant molecules The ese molecules are the enzyme's substates - In some reaction one substrate is broken down into multiple produce. In other, tivo substrates come to gether to create one larger molecule or to swap pieces, in fact whatever type of biological .. reaction you can think of, there is sprobablyth an enzyme to speed it up, CamScanner

as The ciboric acid cycle (Ac)) - also known the TEA cycle (tricarboxylic acid pele) on the lerrebs cycle. is series of Chemical geactions used by all acrobre organisms to release stored enery through the onidation of acetyl-COA derived from carbohydrates a fats, and proteins into adenosine triphosphate (ATP) and Carbon diaxide.. - The citric acid cycle is a key metabolic palkway that connects Carbohy drake, fat and protein orectabolism , the reaction of the cycle are carried out bay eight enzymes that completly oxidize acetate (a two .. Carbon . molecule), in the form of acetal - Con into two each of carbon molecules - dioxide and water. - Through catabolism of sugar; fats and proteins, the two-carbon organic product åcetyl - con is produced which enters the citric acid cycle.. ~). The reaction of the cycle also convert cs Threench equivalents of nicotimamide

valent ie. adenine dinucleatide (MAD) into three equivalent of RADHA and one equiva each of guanosine diphosphate (GPP) norganic phosphate (Pi) into one equivalent of guanosine triphosphate Carp). - the Naom. and FADIA generated by the citric acid cycle are, in form, used by the ocidation phosphorylahon pathway to generale energy rich ATP. - one of the primary source of acetýl acon is from the breakdown of sugars by glycolysis which Yield pyruvate, that in torn is decarboxy tated. lay the pyruva -te dehydoro genase complexe generation acelyl con according to the following reactions Scheme: - CH₃C (20)c (20)5 THS COA INADT > CH₃E (70) Scoot + NADH + CO2 ** An understanding of metabolic .. pathways based solely on bio chemistry textbooks would underestimate the pervasive role of metabolism is essentially CamScanner

every aspect of biology It is evident from reeent work that many human disease. . Involve abnormal metabolic state- Often genelically programmed that pestorb normal physiology and lead to severe tissue dycfunction understanding / these metabolic is now crusial brantion in disease the broad input of metabolism! in cellular function, → Metabolism is broadly defined as the dum of biochemical processes in living organisms that either produce or consume energy. ₂. It is a downtingly large bom: more than 700 reactions and 16000 metaboliks are now annotated in the Kyoto - Core metabolism can be simplified to those pathways, involving abundent nutrients like carbohydrates, falty acids and amino acids, essential for energy homeostasis and macromoleculer days thesis in hineams, pathways of core metabolism ccan be then be seperated Conamiently CU

into three classes: those that says thes simple molecules or polymerize them into more complex macromoleculkens are those that degrade molecules to release energy, → And those that help eliminate the toaie waste produced by the other elasses . . These pathways are profoundly importa tant stated blontly, there are the sole source of energy that allow life to resist the ungs to degirade into entrope Scanned with CamScanner