Chapter 30: The Integration of Metabolism

A review of the principal themes of metabolism is provided in this chapter, which concludes the two major sections of the text devoted to me tabolism.

The chapter begins with a recapitulation of the roles of the building blocks derived from fuels.
The regulatory mechanisms that control metabolism are reviewed.

The major pathways of metabolism are reviewed by the authors, as well as their principal sites of control.

The roles of pyruvate, acetyl CoA, andglucose 6-phosphate as key intermediates at junctions between the various metabolic pathways are discussed.
The major organs' metabolism is presented next.

The authors looked at the ways in which the body responds to certain conditions, such as the well-fed state, the early fast state, and the refed state.

Maintaining a blood-glucose level above 2.2 mM is one of the priorities of metabolism in starvation, which is discussed in this article.
The role of the hormones leptin and insulin in the regulation of calories is discussed.
The authors looked at the fuel choices that the body makes during exercise and how those choices differ between aerobic and anaerobic activity.
The chapter ends with the ways in which excess consumption can affect the metabolism of energy in the body.

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

Discuss the pathways that lead to the rise of glucose 6-phosphate.

List the fuels used by the liver.

Discuss the changes in metabolism that occur after a long period of starvation.

The inhibition of carnitine acyltransferase I by malonyl CoA is an example of metabolic regulation.

The carnitine acyltransferase I is involved in the regulation of fatty acid biosynthesis.

Match the three key intermediates in the left column with their major intermediates in the right column.

The most direct relationships are those not separated by other key intermediates.

The metabolism of each organ, tissue, or cell is described in the left column.

Use an "S" to indicate the following metabolic processes that are stimulated by and an "I" to indicate those that are not.

A normal person's blood-glucose level after an overnight fast is 80 percent.

After a meal that is rich inCarbohydrate, it rises to about 120 g/l and then falls to the fast level.

Match the fuel storage forms in the left column with the ones in the right column.

List the pathways and sources that decrease the pro duction rate during strenuous exercise.

The different effects of glucagon and epinephrine in the body are due to the different properties of the phosphatases that make up the synthesis and degradation of fructose 2,6-bisphosphate.

Chapter 30 cAMP cascade leads to the inhibition of the phosphatase.

The levels of fructose 2,6-bisphosphate are decreased.
The formation of fructose 2,6-bisphosphate is stimulated by the activity of the kinase in muscle.

The synthesis of triacylglycerols requires glycerol 3-phosphate.

The lack of glycerol that is released during triacylglycerol hydrolysis can't be used in adipose cells.
There is need for external suppliedglucose.

The muscles and red cells convert pyruvate into lactone.

pyruvate is mostly used in the liver for gluconeogenesis.

The selection of the pathway depends on whether or not the fatty acids enter the Mito chondrial matrix.

In the fed state, the activity of acetyl CoA carboxylase is stimulated when the concentrations of citrate and ATP are high.
The resulting malonyl CoA, which is a precursor for fatty acid synthesis, is an important component of the oxidation process.

The blood has Glucose removed from it by the liver and by muscle and adipose tissue.

Glucagon maintains blood-glucose levels by promoting gluconeogenesis and glycogen degradation in the liver and by promoting the release of fatty acids, which partially replace glucose as the fuel for many organs.

In people with diabetes, the levels of the two hormones are too low, so after a meal the levels of the two hormones will be higher than in a normal person.

The removal of sugars from the blood will be slower and the levels of sugars in the blood will be higher.

Gluc cose is plentiful, even if ketone body concentrations in blood become high.

The brain usesglucose as its major fuel.

The maximal rate of ATP production is about the same as the rate ofLiver glycogen and adipose tissue fatty acids as fuels for active muscle.

Slow transport of the fuels from the storage sites to the muscle is likely to limit the rate.

The increase in NADH leads to the growth of gluconeogenesis.

NADPH is used by the cytochrome P450 pathway.

When coronary circulation is blocked, the functioning of the cardiac muscle is severely affected.

If the supply of oxygen to heart tissue is reduced, what are the differences between the two?

An infant suffering from a particular type of organic acidemia has frequent attacks of vomiting and lethargy, which are worsened by infections, fast and the consumption of fat.
The patient can be helped by injections of D-3-hydroxybutyrate.
Concentrations of ketone bodies in the blood are very low.
The patient has elevated concentrations of organic acids in their urine and blood.
Three of the acids are 3-hydroxy-3-methylglutarate, b-methylglutaconate, and isovalerate.
From the evidence of the build up of these compounds, the HmG CoA is probably deficient.

After a serious surgical operation, patients who remain unconscious are given 100 to 150 g of glucose daily through a 5% solution.

A biochemist in the Antarctic is cut off from his normal food supplies and is forced to eat animal fat on a diet.

On the day he starts the high-fat diet, he decides to measure his own levels of urinary ketone bodies.

The synthesis of glucokinase is stimulated in the liver.

Within a few days after a fast, nitrogen excretion increases to a high level.

The rate of nitrogen excretion goes to a lower level after a few weeks.

When the body depletes of triacylglycerol stores, the rate of urea and ammonia excretion goes up to a very high level.

There are problems caused by vi tamin deficiencies.

Young men who are championship marathon runners have body fat levels as low as 4%, while casual runners have levels ranging from 12% to 15%.

A 70 kilogram man is expected to burn 2000 kcal of energy per day.

The weight of the two substances is 500 and 180.
The synthesis of one mole of ATP is dependent on the amount of energy generated by one mole of glucose.
40% of the energy from the oxidation of glucose can be used for synthesis.

Explain how the increase would affect each of the pathways below.

In people who have missed one or two meals, the ingestion of moderate amounts of alcohol can cause a rapid rise in blood sugar.

There is a reduced rate of hepatic glucose synthesis, along with increases in ratios of lactate to pyruvate, of glycerol 3-phosphate to dihydroxyacetonephosphate, of glutamate to a-ketoglutarate, and of D-3-hydroxybutyrate to acetoacetate.
A well-fed person with a normal amount of glycogen in their body is less likely to experience a hypoglycemic event.
The rate of production is normal.
There are increases in the ratios of the compounds named above.

There is an increase in the activity of pyruvate carboxylase, which converts pyruvate to oxaloacetate.

There are two reasons why oxaloacetate concentrations should be increased.
The source of pyruvate during starvation should be named.

The Cori cycle is important during early phases of starvation, in which the peripheral tissues are sent to the liver for use in gluconeogenesis.

Oxygen is needed for terminal oxidation of acetyl CoA.

An alternative source of energy can be found in the form of sugar.

Under anaphylactic conditions, the concentration of glucose in cardiac veins will decrease relative to the levels in coronary arteries.

The levels of lactate in the coronary veins are higher than in the coronary arteries.

The inability to convert HMG CoA to acetoacetate leads to an increase in concentrations of 3-hydroxy-3-methylglutarate, which is excreted by the cells.

elevation in the level of acetyl CoA leads to an increase in the concentration of HMG CoA.

Increased demand for blood sugar results in low blood sugar.

Both D-3-Hydroxybutyrate and acetoacetate can be used as fuel for the brain and heart.

The amount of sugar given is limited to prevent the breakdown of muscle.

It serves as a source of energy for the brain and blood cells; otherwise, it is used to provide carbon atoms for the generation of glucose by gluconeogenesis.

A high-fat diet will cause an increase in acetyl CoA concentration, which in turn stimulates the production of ketone bodies.

The profile of ketone body production may be similar to that found during starvation because of the lack of a source of carbon.
The triacylglycerols in body tissue will serve as a source of energy.

When the concentra tions of the hexose are high, glucokinase acts to phosphorylate glucose.

The inability of the liver to control the levels of blood sugar is caused by the failure to synthesise sufficient quantities of glucokinase.

The primary source of carbon atoms for gluconeogenesis is amino acids.

Because the concentration of free amino acids in the tissues is limited, body proteins are broken down to provide the amino acids to support gluconeogenesis.
Nitrogen increases when the excretion of the amino acids is eliminated.

Reduction in gluconeogenesis means a reduction in the rate of oxidation of amino acids and the production of ammonia and urea.

The requirements cause a great increase in the rate of catabolism, with corresponding increases in oxidation and excretion.

A threat to life is caused when more than a kilogram per day in weight is lost.

Most of the vitamins and cofactors discussed in previous chapters of the text would need to be used during starvation.

Among the vitamins needed for those pathways are pyridoxalphosphate, riboflavin, and thiamin.

Palmitoyl CoA is converted to CO2 and H2O in the mitochondria.

It can be used to make ketone bodies.

HMG CoA and cholesterol can be found in the cytosol acetyl CoA.

It can be reoxidized through the action of a dehydrogenase or by the action of a shuttle.

It can be used as a source of amino groups.

It can be used as an amino donor in the cytosol.
It can be used in the cytosol to make glutamine, and it can also be used in the synthesis of new proteins.

The malate-aspartate shuttle serves as an electron carrier in the cytoplasm.

Malate can be used as a source of electrons for the generation of NADPH.

The larger the percentage of body fat, the larger the reserves of triacylglycerols, which are the primary source of metabolism.

The body's breakdown of muscle protein as an energy source is accelerated when the reserves are low.

Many vital body functions can be threatened by excessive muscle tissue destruction.

The amount of energy required to drive the synthesis of 1 mole of ATP is 7.3 kcal.

If 40% can be used to drive the synthesis of ATP, the oxidation of 1 mole of glucose will yield 686 kcal of energy.

The amount of sugar needed per day is 2000 kcal/day.

The normal fuel stores in the blood of a 70 kilogram man are about 250 g and 60 g. The figures show that humans can rely on stores of carbohydrate for a short time.

gluconeogenesis will be stimulated by an increase in oxaloacetate concentration.

When cit rate levels increase, the citrate is shuttled across the mitochondria, where it is a source of CoA.

The formation of malonyl CoA from acetyl CoA allows synthesis of palmitoyl CoA.

An increase in oxaloacetate concentration results in an increase in acetyl CoA concentrations, which could lead to the formation of additional cholesterol.

The oxidation of acetyl CoA is part of the function of the citric acid cycle.

Oxidation or degradation of acetyl CoA can be stimulated by an increase in oxaloacetate concentration.

Net oxidation reactions are suppressed by an increased NADH/NAD+ ratio because the NAD+ needed to serve as an electron acceptor is limited in concentration.

The conversion of lactate to pyruvate, of glycerol 3-phosphate to dihydroxyacetonephosphate, of glutamate to a-ketoglutarate, and of D-3-hydroxybutyrate to acetoacetate will be suppressed by an increase in NADH.

These compounds are converted directly into compounds like pyruvate, a-ketoglutarate, and dihydroxyacetonephosphate, all in the same pathway.

The lack of NAD+ in the cell would result in a low level of production of these and other compounds.
The acetoacetate/D-3-hydroxybutyrate pair is not involved in gluconeogenesis.
Terminal oxidation of these compounds would be affected by the inability to convert D-3-hydroxybutyrate to acetoacetate.

In the event of a drop in blood sugar levels, stored hepatic glycogen serves as a source of sugar.

After 24 to 36 hours of starvation, the body's erythropoietin levels plummet.

The citric acid cycle can operate at higher capacity if more acceptors of acetyl groups from acetyl CoA are provided.

It can oxidize the increasing amounts of acetyl CoA present in the cell.
Oxaloacetate needs to be elevated to provide more precursors for gluconeogenesis.
In order to provide moreglucose to peripheral tissues, the cells of the liver increase their rate of formation through glycogenolysis and gluconeogenesis.
Oxaloacetate molecule availability is the most important factor in determining gluconeogenesis.
alanine is a source of pyruvate during starvation.
Alanine and glutamine act as carriers of carbon atoms and nitrogen.
Alanine is converted to pyruvate by the use of another a-keto acid.

The synthesis of acetoacetyl CoA and b-hydroxybutyrate can only be done with limited amounts of acetyl CoA from fatty chain oxidation.

Carbon atoms from proteolysis would have to be added to sustain the level of gluconeogenesis.

The conversion of pyruvate to alanine means that the electrons that are normally consumed in the conversion of pyruvate to lactate can now be sent to the Mitochondrion.

The brain and muscle do not have the same amount of glucose 6-phosphatase.

The brain and muscle do not release glucose.
The key difference is that acetoacetate has little of the transferase needed to be activated.
The liver exports acetoacetate and 3-hydroxybutyrate to be used by heart muscle, skeletal muscle, and the brain.

The synthesis of triacylglycerols would be affected by a deficiency of hexokinase.

The von Gierke disease is characterized by a high content of glycogen in the body and a low bloodglucose level.

Exercise and fasting cause muscle pains in these people.

The synthesis of glycogen would be affected by a deficiency of glucokinase.

When the blood sugar level is low, the use of acetoacetate as a fuel would be affected.

It will be much slower than normal.

Cerebrospinal fluid has a low content of albumin.

The structure of the membranes would be disrupted.

70 W is equivalent to 0.07 kJ/s.

Let's assume that the electron flow is from O2 to NADH.

The current is 61.4 A, which equates to 3.86 x 1018 electrons per second.

One ATP is formed for every 0.80 electron transferred.

A flow of 3.86 x 1020 electrons per second leads to the generation of 4.83 x 1020 ATP per second or 0.8mmol per second.

The body content of 50 g is equal to 0.099 mol.

When the body is at rest, the ATP turns over once per 125 seconds.

The RQ values are 1.0 (6/6) and 0.703 (51/72).

The RQ of a marathon runner usually goes down during the race.

The shift in fuel from carbohydrate to fat is reflected in the lowering of the RQ.

One gram of tripalmitoylglycerol is equal to 1.24mmol, and one gram of glucose is equal to 180.2mmol.

The H2O yield per gram of fuel is 33.3mmol (0.6 g) forglucose and 60.8mmol (1.09 g) for tripalmitoylglycerol.
The oxidation of this fat gives more water than the oxidation of sugar.
One of the advantages of triacylglycerols is that they can be stored in anhydrous form, which is similar to the way glycogen is stored.

A nut with a mass of 2 g has a value of 18 kcal.

To spend the calories provided by 10 nuts, one would have to run about 31 minutes.

The synthesis of glycogen and triacylglycerols would be late because of a high blood-glucose level.

Poor entry of sugar into cells leads to high levels of diabetes.

The breakdown of lipids to acetyl-CoA is caused by the impaired carbohydrate utilization.
The acetyl-CoA can't be converted to pyruvate orglucose because of a shortage of oxaloacetate.
Some of the Acetyl- CoA will accumulate in the bloodstream.

The brain can use available sugar in the form of glycogen in order to function.

The liver is able to provide its energy needs by using oxidizing fatty acids.

Reactions in both compartments affect electron transfer pathways.

NADH is produced in both the nucleus and the cytoplasm.
The glycerol-phosphate shuttle or malate-aspartate shuttle is what transports the NADH equivalents.
The energy needs of many reactions must be supported by the transport of the ATP produced in the mitochondria to the cytoplasm.

There will be synthesis and storage of triacylglycerols if there is an abundance of sugar and fat in the body.

The poor diet will continue to cause the individual to be deficient in proteins.

As important re covery reactions take place, the oxygen will serve as the ultimate acceptor of electrons.

During the recovery, pyruvate will be converted back into pyruvate and the production of NADH will be stimulated.
NAD+ will be produced by the electron-transport chain when it passes through to oxygen.

Chapter 30 accepts future glycolysis when needed.

Some of the ATP will be used to replenish the supplies of glucose and glycogen in the body.

The machines that are less efficient are the ones that need excess oxygen.

Some of the energy is lost as heat, and additional energy is used because gluconeogenesis is not a chemical reverse of glycolysis.
The resynthesis of glucose from lactate requires more than the production of erythropoietin.

There is a balance between excitatory and inhibitory transmission in the brain.

Alterations in this balance are likely to result in the different effects of ethanol.
The detailed mechanisms are not yet understood.

It is possible to attempt to fix samples under Aerobic and Aerobic conditions.

There could be differences in crossbridge formation for type I fibers in the presence of oxygen.