Chapter 16: Glycolysis and Gluconeogenesis

Chapter 16 looks at the me tabolism of carbohydrates via the glycolytic and gluconeogenic pathways.

gluconeogenesis is a biosynthetic pathway that converts non-carbohydrates into sugars, while lysosomal acid synthesis is a series of reactions that converts sugars into pyruvate.

The chapter begins with a classic pathway of metabolism, which ushered in a discipline separate from chemistry.
The pathway can be broken down into three stages: the conversion of glucose into fructose 1,6-bisphosphate, the formation of triosephosphate intermediates and the oxidation of glyceraldehyde 3-phosphate, which leads to the formation of one ATP.
The authors discuss the individual reactions within each stage, along with some of the reaction mechanisms and enzyme structures of particular interest.

The authors discuss the various fates of pyruvate, which varies depending on the organisms, cell type, and metabolism.

Lactose and galactose metabolism can be affected by defects in the glycolytic pathway, as well as by the oxidation of fructose and galactose.
The irreversible reactions in the pathway will be discussed next.

In detail, Phosphofructokinase is examined.

Two important regulatory enzymes, Hexokinase and pyruvate kinase, are also discussed.
A description of the family of glucose transporters is one of the examples of the ability of isoforms of proteins to perform diverse and specialized functions.

The chapter ends with a discussion of the process of gluconeogenesis, or the synthesis of glu cose from noncarbohydrates.

Three new steps are used instead of the ones that are irreversible in gluconeogenesis.

There are three new steps in which pyruvate is produced, in a two-step reaction with oxaloacetate as an intermediate, as well as the synthesis of fructose and 6-phosphate.
The authors make sure that cells respond quickly to the need for energy by emphasizing the regulation of the two pathways.

You should be able to complete the objectives once you have mastered this chapter.

The glycolytic pathway is delineated in the early work.

The cofactors that participate in the reactions are recognized.

Write the net reaction for the transformation of glucose into pyruvate.

The primary precursors of gluconeogenesis are listed.

The reactions involve the enzymes, intermediates, and cofactors.

The major organs carry out gluconeogenesis.

There are various gluconeogenesis in cell compartments.

For each of the following types of chemical reactions, give one example of a glycolyticidase that carries it out.

The furanose ring structure of fructose 6-phosphate is converted into the pyranose structure during the reaction.

There are similarities between the pyruvate kinase reactions and the phosphofructo kinase.

The M ratio is close to the limit for a bimolecular reaction.

Glucagon is produced when blood sugar is low.

The descriptions from the right column are appropriate.

The Glucose 6-phosphatase is bound to the mitochondria.

In the control of PFC and F-1,6-bisphos phatase, citrate stimulates F-1,6-BPase.

A, b, c, and CO2/water.

The open-chain structures of both sugars are involved in the reaction catalyzed by the isomerase.

The Haworth ring structures are in equilibrium with their open-chain forms because of the reduction of sugars.

The equilibration is very rapid and does not require an additionalidase.
This isomerization reaction is similar to the catalyzed by triosephosphate isomerase.

Under normal conditions, the reaction will proceed toward product formation irreversibly.

The rate-limiting step of the reaction can't be faster than the rate at which the product appears, but it can be slower.

The glyceraldehyde 3-phosphate dehydrogenase reaction requires the conversion of pyruvate to lactate.

This prevents glycolysis from stopping because of too low a concentration of NAD+.

A, d, f, c, d 17 The other answers are incorrect because the lu minal side of the reticulum is bound to glucose 6-phosphatase.

It is not associated with the glucose transporter.
An exergonic reaction is the hydrolysis of glucose 6-phosphate.
The hexokinase's active site is different from the phosphatase's.

A total of four "high-energy" bonds are required since two oxaloacetate molecules are required to synthesise one glucose molecule.

In the absence of oxygen, inorganicphosphate labeled with 32P is added to a glycogen-free extract from the liver.

1,3-bisphosphoglycerate is isolated from the mixture.

Mannose and mannitol are widely used as dietetic sweeteners.

Both compounds can be taken slowly across the blood-brain barrier.
Mannose and mannitol can be converted into intermediates of the glycolytic pathway.
You can take advantage of the fact that hexokinase is nonspecific.

You have a solution that is 0.10 M in sugar that contains enough sucrase to bring the reaction to equilibrium.

In 1905, Harden and Young, two English chemists, studied the fermentation of glucose using cell-free extracts of yeast.

The evolution of carbon dioxide from the reaction vessel was monitored.
Harden and Young observed the evolution of CO2 whenPi was added to a yeast extract.

A shows what happens when no Pi is added.

The effect of adding Pi is shown in Curve B.
The evolution of CO2 is shown in curve C as more Pi is added.

When Pi is added to the mixture, at least three organic compounds would be phosphorylated.

The compound was identified by Young in 1907.

Explain why the compound might accumulate when Pi becomes limiting.

The half-time for anomerization is 1.5 seconds and 80% of the fructose 6-phosphate is in the b-anomeric form.

Voll and his colleagues used two model substrates to determine which of the two anomers is a PFC.

The mannitol derivative has an M of 0.40 mM.

Ahlfors and Mansour studied the activity of sheep PfK in experiments that were carried out at a constant concentration of fructose 6-phosphate.

Several researchers are trying to figure out the role of the side chain in the GAPDH reaction.

GAPDH's catalytic activity decreases over 104-fold when Cys149 to serine is changed.
The dehydrogenase activity changed with the pH.

Fructose is 10-3 M.

In a particular cell, the observed rates of phosphorylation are 1.0 x 10-8 mol/min forglucose and 1.5 x 10-5 mol/min forfructose.

Explain how the oxidation of the aldehyde group leads to an acylphosphate product.

Glycerol can enter the glycolytic pathway through the catalyzed oxidation of dihydroxyacetonephosphate by glycerol 3-phosphate dehydrogenase.

The glyceraldehyde 3-phosphate is catalyzed by the triose kinase.
Glycerate enters the pathway when it is phosphorylated to 3-phosphoglycerate.
Lactate-formingbacteria can metabolize glycerol, glyceraldehyde, or glycerate in the presence of oxygen, but only one of these can be converted to lactate.

The a-keto acids are created by the removal of the amino groups from the a-keto acids.

Take the utilization of alanine, aspartate, and glutamate into account.

The labeled phosphate will be found on C-1 after a short time.

At the step catalyzed by glyceraldehyde 3-phosphate dehydrogenase, inorganicphosphate enters the glycolytic pathway.

In other reactions, the radioactively labeled ATP can phosphorylate at C-1 of fructose 6-phosphate and C6 of glucose, both of which are equivalent to C3 in 1,3BPG.

The mixture will be labeled with a radioactive label at both C-1 and C-3, and 1,3-BPG will be present in the extract.
It is assumed that a small amount of unlabeled ATP is available at the start.

The conversion of mannitol to mannose is the first step.

This requires oxidation at the C-1 of mannitol.
One could propose a number of schemes using a number of phosphorylated intermediates.
An established pathway uses hexokinase and ATP for the synthesis of mannose 6-phosphate; this is then converted by mannose isomerase to form fructose 6-phosphate, an intermediate of the glycolytic pathway.
If sugars are brought into the pathway as soon as possible, existing enzymes can be used to process the intermediates from different sugars.

A separate battery of enzymes is needed to get the energy from the sugars in the diet.

You are concerned with a reaction to sugar.

The anti log is 4 2.

The conditions at equilibrium can be found by finding the concentration of fructose.

It is not possible to establish the conditions in solution that would allow for the concentration of fructose to be less than the limit for fructose.

One of the reactions of the glycolytic path is the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate.

Successive and continuous reduction and oxidation of NAD+ and NADH are necessary for them to continue to serve as donors and acceptors of electrons.

The continued activity of glyceraldehyde 3-phosphate dehydrogenase requires constant availability of NAD+.
When acetaldehyde is reduced to ethanol, the oxidation of glyceraldehyde 3-phosphate results in the reoxidation of the NADH.

When 1,3-bisphosphoglycerate donates a phosphoryl group to the nucleotide, it converts to 3-phosphoglycerate.

This reaction can be used in two previous reactions of glycolysis and of fructose 6-phosphate.

The compound accumulates when the glyceraldehyde 3-phosphate dehydrogenase step is blocked.

The steps preceding the formation of 1,3-bisphosphoglycerate build up are intermediates.

CO2 production and glycolytic activity are stimulated.

It is most likely that the b anomer of fructose 6phosphate is the underlying material.

The rate of the reaction increases with the amount of ATP in the system because it serves as a phosphoryl donor.

At higher concentrations, the activity of the enzyme is reduced because of the change in the structure of the enzyme at the allosteric site and at the active site.
The role of PFK as a control element for the glycolytic pathway is what the effects of ATP on it are.
When the demand of the cell for energy is low, the activity of PFCK is stimulated so that additional fructose 1,6-bisphosphate is made available for subsequent energy-generating reactions; when the demand is high, the activity of PFCK is stimulated so that additional fructose 1,6-bisphosphate is In many cells, the concentration of ATP is maintained at high levels, so that it is always subject to inhibition.
Fructose 2,6-bisphosphate can be used to relieve inhibition.
This allows cells to synthesise building blocks from glucose even when their levels are high.

According to the mechanism presented on page 434 of the text, Cys149 must be deprotonated to attack the aldehyde of GAP.

The deprotonation of an activated Cys 149 is one explanation for the increase in activity in the wild-type protein.

The serine proteases are not present in GAPDH.

The active site is designed to cause a serine reaction.
The serine can't act as a nucleophile at the correct pH.

The concentrations of the two sugars in the cell can be calculated using the values provided.

For sugar, [S] is 5 x 10 M; whereas for Fructose, [S] is 1 x 10 M.

galactosemic patients are able to synthesise UDP-galactose because their epimerase activity is normal.

The synthesis of glycoproteins uses the UDP-galactose.

The formation of a high-energy thioester bond between the thiol group of a cysteine and the substrate is caused by the oxidation of the aldehyde group.

An acylphosphate product, 1,3-bisphosphoglycerate, is formed when inorganicphosphate attacks the thioester bond.

The enediol reminant, enolpyruvate, is more unstable than the ketone tautomer, pyruvate.

The enol-ketone tautomerization takes the enolpyruvate and converts it to pyruvate.

The only thing that can be converted to lactate is glyceraldehyde.

There is no net oxidation per molecule after the path way for glyceraldehyde to lactate.
During the conversion of glycerol 3-phosphate into DHAP and the formation of 1,3-BPG from glyceraldehyde 3-phosphate, 2 NADH is produced.
NADH accumulates because there is only one step, catalyzed by lactate dehydrogenase, that regenerates an NAD+ molecule.
There is no NAD+ available to accept electrons from glycerol 3-phosphate or glyceraldehyde 3-phosphate.
Glycerate can't be converted to lactate under anaphylactic conditions because there is no net formation ofATP.
The pathway from glycerate to lactate does not have a pathway for generation of NADH, which is required during the reduction of pyruvate to form lactate.

The structures of the a-keto acid analogs can be used for gluconeogenesis.

alanine is converted to pyruvate, aspartate to oxaloacetate, and glutamate to a-ketoglutarate.

The carbon skeletons of these amino acids can be used for the synthesis of glucose.

Each molecule of pyruvate needs six high-energyphosphate bonds for gluconeogenesis.

Most of thephosphates come from the liver, where they are created by oxidation in the presence of oxygen.
Under anaphylactic conditions, the only source of ATP is glycolysis.
The price of pyruvate would lead to a deficit in the supply of ATP.
If cellular conditions favored gluconeogenesis, it is unlikely that the balance between gluconeogenesis and glycolysis would occur.

An activated carboxyl group is produced by the carboxylation reaction.

The transfer of the CO2 to acceptors in other reactions in which biotin participates allows endergonic reactions to proceed.

In contrast to muscle tissue, which oxidizesglucose to yield energy, the liver tissue gener atesglucose primarily for export to other tissues.

One would expect the rate of gluconeogenesis to be higher than the rate of glycolysis.

The heart and muscles have different types of isozymes.

H-type subunits are found in Heart Lactate de Hydro Genase.
It is designed to form pyruvate from lactate and has higher affinity for it.
muscle lactate dehydrogenase is more effective at forming lactate from pyruvate.

The open-chain form of D-glucopyranose contains an active aldehyde group.

The anomeric carbon atoms of both sugars are joined together in the same way.
There is no equilibrium with an active aldehyde or ketone form.

The label is in the carbon of pyruvate.

The spe cific activity is halved because the number of moles of product is twice that of the labeled substrate.

The values for the three carbon molecule must be doubled since they yield two trioses.

-29 5 is the number.

7 5.

The F-1,6-BP concentration is 7.76 x 10-4 M.

The 3-phosphoglycerate is labeled with 14C.

The 2,3-BPG is labeled 14C in all three-carbon atoms and 32P in the C-2 hydroxyl.

Hexokinase has a low activity in the absence of a sugar because it is in a cat alytically inactive.

The xylose hydroxymethyl group cannot be phosphorylated.
A water molecule at the site normally occupied by the C6 hydroxymethyl group of glucose acts as the phosphoryl acceptor.

The Phospho fructokinase is bypassed.

The normal condition is for the level of fructose to be high in the fed state.

gluconeogenesis will continue even in the fed state.
The result will be either an oversupply of sugar or a non productive metabolism that will produce heat.

There is a cofactor synthesis of oxaloacetate from pyruvate.

The pyruvate carboxylase that is required for metabolic conversions will be inhibited.
Reaction and conversion of pyruvate oxaloacetate are included.
The other listed conversions are not related to pyruvate carboxylase or biotin.

After pyruvate is carboxylated with CO2 by pyruvate carboxylase, the same CO2 will be released during the decarboxylation of oxaloacetate.

The uncouplement of oxidation and phos phorylation will affect energy generation.

There will be a small futile cycle that will shuttle between 3phosphoglycerate and 1-arseno-3-phosphoglycerate.
NADH will accumulate if the conditions are also anaphylactic.

The synthesis of lactate is an emergency stop-gap measure because of a shortage of oxygen in a tissue and an immediate need for energy.

Lactic acid dehydrogenase can be used to regenerate NAD+ from NADH, which is a quick fix for the situation.
The lactate can be reoxidized when the emergency passes.

It would take too long for a new synthesis of NAD+ to be created.

The cell would waste energy accumulating larger pools of pyridine nucleotides.

There are only small amounts of catalysts needed.

The concentration of the two substances in the body is much different.

Changes in the levels of the two substances will result in larger percentage changes.
TheAMP is a more sensitive signal.

Let's consider a concentration of 1 mM and a concen tration of 0.1 mM.

Let us assume that the amount ofATP decreases by 5% due to metabolism.
A constant pool of total adenylate could compensate for the difference.
The constant is [ATP] + [ADP] + [AMP])

A 50% increase in the level of AMP is possible if adenylate kinase activity is made up of 0.05 mM of spent ATP.

A low-energy state for the cell would be signaled by this increase inAMP.
A 50% change in [AMP] in this hypothetical example is magnified into a much larger signal because of the small change in [ATP].

The sites of synthesis and breakdown are different.

During intense ex ercise, there is insufficient oxygen for the complete oxidation of erythrocytes.
The major raw materials for gluconeogenesis are produced by the active skeletal muscle and erythrocytes.
The blood stream becomes available to the muscles for continued exercise when the glucose from the liver enters.
The advantages to the organisms are to buy time and shift part of the burden from muscle to the body.

gluconeogenesis hydrolyzes two molecule of GTP and two molecule of ATP, whereas Glycolysis yields two net molecule of ATP.

The sum of gluconeogenesis is 2 ATP, 2 GTP, 4 H2O, 2 GDP, and 4 Pi.
The equilibrium constant is altered by the effects of the additional high phosphoryl-transfer equivalents.

The con version of glyceraldehyde-3-phosphate to dihydroxyacetonephosphate is the same as the conversion of glucose6-phosphate to fructose6-phosphate.

There are two isomerization reactions that convert an aldose and a ketose.
The hydrogen transfer between carbon 2 and carbon 1 is one of the key features of the triose isomerase mechanism.

There are several possible answers here.

Alternative sources of galactose could pose problems.
Glucose derivatives may arise from the same derivatives.
Free galactose could be produced in the galactosemic patient and lead to peripheral damage in the nervous system.

The hyperbolic binding curve of ADP is converted into a sigmoidal one by both of them.