Enzymatic control of glycogen metabolism

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Enzymatic control of glycogen metabolism
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she's. to. well. the. it for you playing introduction the subject and children is a genuine and has to do with the control of blood sugar the supply of energy for work and the storage of excess carbon hydrate in tissues. the deals with says she's a logical and bar chemical problem and it's also of some importance for the clinic. i hope i will be excused if many of the losses like world of four month students and collaborators and it's not very presentation be be divided into three parts one having to do with the structure of like region.
the other with its and cinematic sentences and degradation presentation of the be divided into three parts one having to do with the structure of black region. the other with its and thematic sentences and degradation. understood problem dr for regulation. not in the time available i can probably only touch briefly in each of the subject and i would like to ask the chairman dr are hard and to interrupt me if i exceed the time i might get one up and lose track of time to know.
oxygen was discovered or were hundred years ago a lot going on. you deserve probably soccer at present in all teachers but it's especially important in deliver where it says as a source of blood sugar and in muscle where it serves as a source of energy from muscular work.
so if you simple facts about like when it is composed entirely of glucose units and there are two types of linkages present. and out from one for omar to see big linkage in linear portions of to moan acumen and our home on six lucas he didn't have at their points of ground and in fact sliding still it's the structure is similar. to that of emotive branched treat.
the molecular of eight is love seven million or more and is distributed over a wide range of and because of this large size package and cannot pass the cellular member ins and in order to be available. bubble to the organism it has to be broken down by into cellular and search and just brings me to the consideration of the enzymes involved in like region metabolism. not achieve enzyme for like and integration is a force for oil is which dr i have mentioned it splits the out from one for bone have liked and in phosphor only tickly that is in organic profit rackets and.
the product is a force for later trigger glucose one last bit of a group from forcefully office for all his begins its degradation at the outer chains of placards in removing one look was unit at the time of glucose one phosphate but many approaches a branch. point. and if attacking still the the its action is stopped under separate enzyme is needed to deal with tough a month six locals unit at branch ports just the branch and entitled.
it has a dual function it acts first as a chance for years removing some new clothes units which still come with a branch or group of units and plant first into other chain then it act as a group wasn't his have lived under one six boeing. so the two ends i was flawless and dancing and acting together degrade glycogen completely under products up to postman phosphate from the arts woman full linked because units and free group was from the ottoman six.
unit and branch poise and by using these two enzymes separately and consecutively one gets a step was to the addition of dark wooden much as one would leave when the branches a tea and displayed inside introduce structure of plaque engine in fact. it was was to end of peace to end sense that the motor branch tree like structure of black president but first really are starved although it had been for just a good sort of talk like that just been age my eyes on the also supports us looked.
now it's into his of placards will also require us to and nine while ford after month for moans and to afford our someone six points off the farm and been discovered van and while transference a glucose still unit for immunity in the hospital cause. dune existing polly all he saw current change does enzyme can only make limits change in the presence of a branching and and the whole chain unity shifted in attached to a neighbour and failure in one six linked.
not all these every three to end to this involves and now i would like to illustrate some of the points made in the end of slides could i have to have slightly. we are shown here. and particles of dark engine vigilance an electron microscope in these are glycogen particles present in muscle and reason or shoulder slide is to indicate that the glycogen is located in the spaces between demand of fiber of.
where they also mitochondria present u.c.u. mitochondria and surrounded by glycogen particles these are the so-called better particles described the truffles an electron microscope its and so the chemical events in mosul take place in days rather narrow spaces between demand for britain. there's very little if any glycogen present in the mouth hamburgers and our next slide.
scholz glycogen in deliver and hear the better part of course of muscle glycogen are combined in the thought of their shows that there is already a structure to the glycogen liver differs from muscle glycogen by as much greater molecular might actually dish picture is from a child suffering from. type two decades in storage disease but it's structured entirely normal and serves to illustrate the age to rosettes i do not know about this not to concede him but several better particles combine to form these large structures not as black agenda.
so large that it can be easily centrifuge out of the little homogenized and understand found that the particles absorb most of the end and not act on it that is the particles contain for for oil is sent it is branching into the branch. thing and then and recently fisher and study in the years and i could be an enzyme complexes in muscle and he had found that the exhibit under certain conditions quite different kinetic behavior.
from solihull and them systems and this finding may turn out to be quite important for the operation of the system on the enviable conditions now let's look at the ends up the next slightly of knowledge this is the first floor later. the action what you see here is the out to chain of glycogen link up from one phone and first foreign lands and phosphate instead of one phosphate instead of water is involved in the bone.
braking and this mixed reaction easily reversible the audience for strollers can either remove because units one at the time converting it to glucose one phosphate or it can lead to cause units one at that time from. some locals among philosophy of and like city's first from loneliness can only me a linear chain and likes into details it cannot really stop a change in overall but most build on to the existing faints now.
one reason why a first for a place inside the seller is mainly used for degradation is the following in organic phosphate a product of their the action in the deduction of synthesis that is when the glucose part of group. because one profit is added phosphate is set free because phosphate is the product of synthesis it would have to be removed as rapidly as it if phone if sentences is to continue. no the concentrations of inorganic phosphate the ratio of inorganic phosphate to google's one phosphate it's on favorable inside of most cells in the next slide ritual how nature overcame this difficulty this issue.
redeemed of phosphate look almost a compound discovered by little are which have phoned in n.z. matic interaction between blue culled from phosphate in your and imply phosphate and in fact this is a loophole someone phosphate linked to a power of friendship group do you really asked to know. of this compound of the he the situationist term a dynamic really much more favorable and we can see does in the next line where the equilibrium of the two reactions are compared the reaction to catalyze by for fraud.
first and by your a deal but the transfer rates of local from the u d p g to an existing chain the end here stands for glycogen was and glucose units and out the chain nominee right to equilibrium expression the concentration of black or asian drops out because.
g n group of the black agendas and locals unit if you add one more one appearing to nominate and on and innumerate the drops out so if we look at the equilibrium of inorganic foster to glucose one fostered we found a new equilibrium plaudits means that the rate of. the to free energy of hundred sheets of glucose one fostered is roughly equal to that of them out to see that on and so direction as usual reversible on the other hand about five quito calories per more is to free and you have had grown says of glucose one phosphate on the other hand to free energy of how gross its.
of the glucose in good enough for us for glucose is about its fuel colourist for more than just mixture their actual practically irreversible and this is much higher free energy have had a role it's this explains why so many like a suit can ferry arts. since involved nucleotide link figures as like a single donor as little was discovery of these reactions with nucleotide link sugars was suddenly and most important party chang one and has just really been undone by and they have ordered the nobel prize a few years.
ago knowledge or next slide i would like to discuss next enzyme and would like to discuss his study branching and time and here we have various kinetic picture of an outer part of glycogen molecules here do month fall in local communities another branch human. it's better than six link which occurs and you see the molecule lose arrangement two years until you come to italy one reducing and its bird in a very large molecules office for his as i said that removes mongol cause unit at a time around all these chains about it.
eventually stops but it approaches to branch on unit it from to limit extreme and to be deliberate extreme was shot out to change its know the next line. shows what these limits extreme looks like you see that it has just a branch point will cause unit to reduce carbon by three locals units and the the branching enzyme first acts as a transfer is it takes three google's units and puts them. i'm in this manner dead by freeing use google's units reduced and how to live off of free glucose now the question is whether one or two enzymes i'm ball and with has interest and on laboratory for a long time and effort to.
clearly the browns have purify an enzyme extensively and have treated it recently agents known to disassociate proteins but so far they have not been able to separate the to work to be used to transfer activity india had a little activity. the and spirit of much work that has been done during purification of the enzyme on after it is practically pure it took to it is obvious stay together.
and so the question is still raised their two chains on which are difficult to separate because even you really don't separate them or i.v. dealing with the unusual case of a two headed end them. the latter is possible if you imagine that the code word for stop would drop out between two addition polyp uptight change in the met might found one chain was to cut a little heads but another saw not have still to be investigated what to do.
an interesting problem not the last and on show is to branching and time an excellent is and the the basic action of the wrenching action was demonstrated by loughner he first the greater part of an incompletely and added label. about to change units in destruction hear the one six units are not labeled but when you add to disturb wrenching and time it will cut one for unit and the tattooed one six and you can demonstrate that this is taking place because no use wrenching you.
it's a label to was carbon fourteen so this is the basic action and for violent one of more about the details of his action and not continue to discuss it and i'm merely want to say that the action pattern of the city's of lunar rocks into it is lost. up of branching and then explains the structure of the structural characteristics of packaging. now the detail of knowledge of these enzymes is of importance for an understanding not only of regulation but also of certain and added terry disease in men were each of these for any of them and have been found or you can take off the slightly.
that may each of these four and as has been found to be missing a very low in individuals homozygous for the of normal gene. that may not be time enough to deal with these genetic disease except perhaps to give one or two examples if they the benching and i'm is missing in a call of clout couldn't cannot be degraded because full fro his kennel bypass the branch points and is enough.
because of lacquered in accumulating the tissues and one can diagnose the disease simply by doing the structural analysis of the glycogen because the haka chained of just like urgent up normally shop and they approach the structure of to limit the next. in that i have shown on the other hand when the branching and them is missing and this is another their genetic disease the glycogen change or if the end them is very little bit like wouldn't change become of normally long and that i owed in color is no purple to bluish like doctors.
stop so i mean look packed in their to the ranch component of starch and not the bug in the red of factors and so these are just two examples where one have repeated knowledge of and then has to understand of normality. when i mean not have time to deal with this but would rather now stop is a discussion of regulation of package in metabolism and as a gentle remarked i would like to say that regulatory mechanisms are of.
increasing a very great in increasing importance in biology and medicine. but there are difficult to investigate so radically man should do on experiments an impact if years but does limit civilly experimental possibilities. another difficulty is the on certainty involved in extra pollution from in vitro couldn't leave of conditions from the test tube to the functioning of the ends and south within the organisation of the self.
no i would like to illustrate this particular difficult in the case of his furnace and its function during muscular contact. i'm not speaking about regulation in muscle and if i may have to next line we see here folks for this occurring into farms term for trollish be and eight and one to be phone is converted to the iphone by. there is specific for strollers be kindness which puts of phosphate group on mum of this area known as it used in the poll he kept a chain and it is converted back to be from my defence furtive which specifically removes.
d.'s phosphate groups and most forms of the enzyme in a better mother died merrick liberal although the iphone has more tendency to form a tantrum it and to be phone and does step them and i may include new may play a role. in regulation because the diameter of each form is much catalytic lee much more active than the title were not.
it's difficult to judge in what form the enzymes occurs in the tissue since these that a maritime the equivalent depends on the number of factors which one does not know about intact sell no resting muscle contains all of the first pro bowlers in to be foam. to prove this required very special technique because these kindness and properties act was tremendous rapidity should require special fixation and extraction techniques to demonstrate that and to be foam it's completely inactive cartilage.
typically the healers diameter trauma unless it is in contact with an elite acid known the activation by an elite acid have to be from involves an outpost eric modification of the enzyme such that the enzyme acquires created a few. city for substrate glycogen inorganic phosphate and this activating effect of other nearly acid of a m p is competitively inhibited by an illness in dying entire footage future president into shoes not the iphone differs from the.
the form by being catalytic lee active per se he ordered his influence also about a new gas it body in his activity without being in contact with at the newcastle and it is not inhibited by eating a d p o eight the peak of novels such detailed information available. well and i'm has now been studied for thirty years by many workers and one owns of calls about the mikhail is constant became more subdued active it was an inhibitor and one knows what the concentrations are indeed also money should be able to reconstruct an in vitro model.
it would explain muscular activity during which have cost of frost for all its activity has to increase in placards in have to be broken down so the next slide is such an attempt to reconstruct their model and now you see here the velocity of the enzyme reaching hundred percent. cent when it is fully active in here you have to concentration of inorganic phosphate the arrow is to concentration of inorganic phosphate in arresting fraud mosul the concentration in the into several water calculated not for the external concentration foot would pull.
the concentration in the into solar water and where the arrow his studies to normal concentration not under top curved assumption has been made that the enzyme is in contact with stark region which is present in excess anywhere you she were just sitting in the spaces and it is in contract was in organic. phosphate and was at in munich acid which is present in mosul other concentration of point five million dollars which would be about ten times that came while you for the answer no this cannot be do situation in muscle because if you ring stimulation in order.
and it forced to bear to increase we would only have a very slight increase in full from oil is activity from here to hear we know however that from lactic acid formation that the glycogen breakdown most increased ten twenty or more times during stimulation not under certain curb here. we have made assumptions that the end them is in contact not only would have been in the gas it would also was eighty p. ten million more will actually do some of a.t.p. an a.t.p. being present in muscle and here we get in as shaped curve as indicated by the here because of fish and of two and here at least we have.
reasonably lot to bt in wrestling muscle after his concentration of inorganic phosphate but you can also see that we would have to have very large changes in concentration in order to increase activity in organic first feared would have to triple boeing a.t.p. eighty people have to go down and. it's dr hamer through the rich group who worked with me for many years and since those we have started very carefully about concentration changes one gets in these reactions the note read found for example of that when we stimulated problem mosul.
but the eighteen shocks per minute eighteen concoctions per minute for thirty minutes which increased the like did formation searching for old we could not find sufficient changes in the concentration of these direct and to explain such an increase in front for. more effective efficient so that we came to the jungle conclusion that i lost eric regulation alone you feel the other study this is an expression of the co-operative you do have to subdue units of the tougher for only be the ulster nick regulation alone cannot account for the club.
crowe of glycol insists during muscular contract from the legal system that we have set up here on the basis of our good knowledge we have about the enzyme appears to be inadequate to represent the events during muscular contraction.