Metabolic Integration - General

Question 1

The body has three potential types of stored fuel that can be accessed when needed and then replenished when dietary sources become available. What are these and what are they a source of?

Answer 1

1. Glycogen: source of glucose
2. Triacylglycerol: source of fatty acids
3. Protein: not a storage form but can provide amino acids

Question 2

Nearly all of the glycogen stores in the body (300-600g) are present in _____ and _____, with _____ stores being about twice as large as the other.

Answer 2

Liver, muscle, muscle

Question 3

Is glycogen water soluble? How is it stored?

Answer 3

Glycogen is water-soluble, it has a fair bit of water that is stored with it, almost 2-3X the weight of glycogen itself.

Question 4

Triacylglycerol stored in _____ (and a bit in _____) is the major stored energy source in the body.

Answer 4

Adipose, liver

Question 5

Is there a limit to fat storage?

Answer 5

No

Question 6

Triacylglycerol has a caloric value of ___ kcal/g, more than twice as high as carbohydrates, at ___ kcal/g.

Answer 6

9, 4

Question 7

Fat is water-(soluble/insoluble). What does this essentially mean about fat storage?

Answer 7

Insoluble. There is essentially no water required to store fat

Question 8

Protein will provide _____ for use as _____ precursors in pathophysiological conditions such as _____ and _____.

Answer 8

amino acids, glucose, starvation, diabetes

Question 9

Protein is a potential source of fuel because of the _____ and _____ properties of amino acids.

Answer 9

glucogenic, ketogenic

Question 10

Muscle protein will become an important fuel source for the synthesis of glucose when levels of _____ and _____ become limiting.

Answer 10

glycogen and TAG

Question 11

Protein has a caloric value of ___ Kcal/gram and also stores _____ with it.

Answer 11

4, water

Question 12

All of the nutrients that are absorbed in the small intestine enter into the _____, which flows directly to the liver.

Answer 12

portal vein

Question 13

The _____ is uniquely positioned anatomically to be the central metabolic organ in the body, and possesses most of the major metabolic pathways that we have discussed thus far in this course.

Answer 13

liver

Question 14

A major role of the liver is to produce fuel from the nutrients that it takes up from the blood that can be used by other organs for energy production. What does it use glucose, lactate, alanine and glycerol for?

Answer 14

• Glucose: synthesizes glycogen which it stores until such time that blood glucose levels drop, at which point it is degraded to glucose and released into the blood.
• Lactate and alanine(muscle), andglycerol(adipose): converts them toglucose via gluconeogenesis.

Question 15

What is the primary fuel that the liver uses for itself? What process produces the fuel?

Answer 15

Fatty acids. Fatty acids taken up by the liver can be broken down for energy through 
β-oxidation.

Question 16

Excess fatty acids are converted to _____ or _____, packaged into _____, and exported out to peripheral tissues.

Answer 16

cholesterol esters, triacylglycerol, lipoproteins

Question 17

A major role of the liver is to act as a _____ sensor and regulate _____ levels.

Answer 17

glucose, blood glucose

Question 18

Chronic elevated levels of glucose, such as is seen in untreated or poorly managed diabetes, causes damage to what?

Answer 18

Damage to the endothelium of blood vessels and to nerves.

Question 19

If blood sugar levels fall too low (hypoglycemia), it can lead to these 5 things.

Answer 19

1. Weakness
2. Dizziness
3. Shakiness
4. Confusion
5. Coma

Question 20

What are the 3 specific features the liver has that make it a good glucose sensor?

Answer 20

1. Specific glucose transporter (GLUT2) which has a high K_m for glucose, meaning that glucose uptake into the liver is only increased significantly when glucose levels are high.
2. Hexokinase isoform, called glucokinase, also has a high Km for glucose and thus only becomes fully active when glucose levels rise.
3. Glucose binds directly to glycogen phosphorylase a, the phosphorylated active form of the enzyme that degrades glycogen. This increases the susceptibility of the enzyme to dephosphorylation and inactivation, ensuring that as glucose is taken up by the liver, glycogen synthesis is favoured rather than glycogen breakdown

Question 21

The primary role of muscle is to _____, and the ATP required to do so is obtained from the oxidation of a variety of fuels, primarily these 3:

Answer 21

Contract.

1. Glucose
2. Fatty acids
3. Ketone bodies

Question 22

The fuel that muscle uses changes significantly depending on the _____ of muscle. Which fuel is used at rest, during exertion and continuous exertion?

Answer 22

Activity.

• Rest: fatty acids from blood
• Exertion: glucose from glycogen breakdown (main) and blood
• Continuous exertion: fatty acids

Question 23

Since muscle lacks this enzyme, the glucose released from glycogen as glucose-1-phosphate has only one route, that to be metabolized through glycolysis and TCA cycle for ATP production.

Answer 23

glucose-6-phosphatase

Question 24

​During continuous exertion, _____ becomes a significant product in muscle due to the fact that the rates of glycolysis exceed that of the TCA cycle. What happens to this product? What is this process called?

Answer 24

Lactate. Lactate is rapidly released from muscle into the blood, which is taken to the liver for use in gluconeogenesis or used by the heart as an energy source through oxidation to CO₂. This is called the Cori Cycle.

Question 25

Outside of the big 3 for fueling muscle, what can be used as a potential source of energy? Why does this usually not occur? What is this potential fuel source usually used for instead?

Answer 25

Muscle protein is another potential source of energy, since protein turnover releases amino acids. Since the breakdown of muscle protein is both harmful to the organism and metabolically wasteful, amino acid catabolism is limited in muscle and instead these amino acids are reutilized for protein synthesis.

Question 26

_____ is by far the largest storage compartment for fuel in the body.

Answer 26

Adipose tissue

Question 27

How long can the fatty acids present in TAG within an individual of average weight sustain that person?

Answer 27

Several months

Question 28

What is the primary role of adipose tissue?

Answer 28

Store fatty acids as triacylglycerol until such time as they are needed as fuel, at which point the triacylglycerol is broken down and the fatty acids released into the blood to be used by other tissues.

Question 29

What happens to glycerol released from fatty acid breakdown?

Answer 29

Released into the blood and taken up by liver where it is use as a substrate for gluconeogenesis (Module 3).

Question 30

Where does the glycerol-3-P come from for triacylglycerol synthesis in adipose?

Answer 30

It comes from the metabolism of glucose through glycolysis to dihydroxyacetone phosphate, which can in turn be converted to glycerol-3-P by glycerol phosphate dehydrogenase (Module 3).

Question 31

The brain consumes about ___% of all glucose utilized by the body and ___% of total energy needs.

Answer 31

60, 15

Question 32

Under normal conditions, _____ is the only fuel the brain uses to generate the large amount of ATP needed for nerve transmission. The brain can switch to _____ as a fuel if glucose becomes in short supply.

Answer 32

Glucose. Ketone bodies.

Question 33

Can the brain use fatty acids as an energy source? Why or why not?

Answer 33

The brain cannot use fatty acids as an energy source, since fatty acids in blood are bound to albumin and cannot cross the blood-brain barrier.

Question 34

Much of this metabolic integration within cells and between organs is mediated by _____. We will focus on the big three:

Answer 34

Hormones

1. Insulin
2. Glucagon
3. Epinephrine

Question 35

Insulin is produced and stored in the _____ and released into circulation in response to what?

Answer 35

Pancreas, increased levels of glucose in the blood

Question 36

Insulin signals the _____ state in the body.

Answer 36

Fed

Question 37

In the fed state, insulin will promote what 3 things?

Answer 37

1. Uptake of diet-supplied nutrients
2. Replenishment of fuel depots
3. Biosynthesis of macromolecules as a result of an increased supply of precursors.

Question 38

One of the primary effects that insulin has is to stimulate glucose uptake into which 2 tissues? How does it do this?

Answer 38

Adipose and muscle. It does so by causing the translocation, or movement, of glucose transporters (specifically GLUT4) from intracellular sites to the plasma membrane, which increases glucose uptake.

Question 39

In liver, insulin increases glucose uptake by stimulating this enzyme, which enhances utilization of glucose in the cell which allows glucose to continue to enter the cell down the concentration gradient.

Answer 39

glucokinase

Question 40

Insulin stimulates glycogen synthesis in both liver and muscle, by both activating _____ and inhibiting _____, the latter being the enzyme that degrades glycogen.

Answer 40

Glycogen synthase, glycogen phosphorylase

Question 41

In liver and muscle, insulin stimulates glycolysis by increasing the activity of _____ and _____. At the same time in liver, insulin inhibits gluconeogenesis by decreasing the activity of _____.

Answer 41

Phosphofructokinase-1, pyruvate dehydrogenase. Fructose 1,6-bisphosphatase

Question 42

In liver, the acetyl CoA produced from enhanced rates of glycolysis is directed towards fatty acid synthesis through to the stimulation of this enzyme by insulin.

Answer 42

acetyl CoA carboxylase

Question 43

In adipose, in addition to stimulating glucose uptake, insulin stimulates conversion of glucose to _____ to which fatty acids are linked to synthesize TAG.

Answer 43

glycerol-3-P

Question 44

It should be apparent that the major organs through which insulin exerts its effects are _____, _____, and _____, three organs that are at the centre of metabolism.

Answer 44

liver, muscle, adipose

Question 45

Glucagon is released by the _____ in response to a drop in blood glucose levels, and its effects on target organs (_____ and _____) reflect the role of this hormone to _____ so that the _____ in particular has an adequate supply of its major fuel.

Answer 45

pancreas, liver, adipose, increase blood glucose levels, brain

Question 46

A major action of glucagon is to stimulate the release of glucose from _____ into the circulation.

Answer 46

liver

Question 47

From what 2 metabolic pathways is the glucose that glucagon targets derived? By which 2 enzymes?

Answer 47

Glycogen degradation and gluconeogenesis contribute to this, through the glucagon-stimulated activation of glycogen phosphorylase and PEP carboxykinase, respectively.

Question 48

Glycolysis is also slowed by inhibition of these two enzymes
; this reduces the use of glucose as a fuel in liver so that it can instead be released into the blood.

Answer 48

phosphofructokinase-1, pyruvate kinase

Question 49

In liver, glucagon also stimulates _____. Describe this process.

Answer 49

Ketogenesis. Ketone bodies are produced which the brain can use as an alternative to glucose in the event that glucose levels do not recover quickly enough in the blood.

Question 50

In adipose tissue, glucagon stimulates fatty acid mobilization and release into the blood by stimulating this enzyme. What does this serve to do?

Answer 50

Hormone-sensitive lipase. This serves to reduce the demand on glucose as a fuel source by providing an abundance of fatty acids that can be used as fuel by other tissues.

Question 51

Where is epinephrine released from? Under what conditions?

Answer 51

The adrenal gland under stressful conditions that require energy.

Question 52

The metabolic effects of epinephrine are exerted on these 3 tissues, and serve to do what?

Answer 52

Liver, muscle and adipose, serving to increase fuel availability and oxidation to produce ATP.

Question 53

In liver, epinephrine stimulates glycogen _____ and inhibits glycogen _____. ​

Answer 53

degradation, synthesis

Question 54

In muscle, epinephrine stimulates glycogen _____ and this pathway, which facilitates what?

Answer 54

Degradation, glycolysis. ATP production from the glucose release

Question 55

In adipose tissue, epinephrine stimulates _____, which provides further fuel for muscle to use in the form of _____.

Answer 55

TAG hydrolysis, fatty acids

Question 56

What is the duration of the effects of epinephrine? What is the duration of the effects of glucagon?

Answer 56

Epinephrine’s effects are short-lived whereas those of glucagon are longer-lasting.

Question 57

In the early phase of starvation what happens to glucose, insulin and glucagon levels? What do the changes in insulin and glucagon cause?

Answer 57

Glucose levels start dropping in the blood, insulin levels drop as well but glucagon levels rise.

The drop in insulin reduces glucose uptake and utilization by muscle, liver and adipose so that glucose is preserved for use by the brain.

Glucagon stimulates gluconeogenesis and glycogen breakdown in the liver, and the glucose released helps maintain blood glucose levels. Glucagon also stimulates TAG hydrolysis in adipose. The fatty acids released are used by muscle, liver and other tissues as fuel rather than glucose, and the glycerol released from adipose is used in liver as a substrate for gluconeogenesis.

Question 58

While some amino acids are likely used as substrates for gluconeogenesis in the early phase of starvation, it isn’t needed to any large degree due to the availability of _____.

Answer 58

glycogen

Question 59

Once in the mid phase of starvation, what has happened to liver glycogen? What is happening to TAG hydrolysis in adipose and how is the glycerol that is released used? Is this amount of glycerol sufficient?

Answer 59

Liver glycogen is depleted, a new phase of metabolic adaptation begins as the body tries to lower its utilization of glucose.

TAG hydrolysis in adipose continues at high rates to provide fatty acids to tissues for energy rather than glucose. The glycerol released from TAG hydrolysis is used by the liver as a substrate for gluconeogenesis.

The amount of glycerol available is insufficient for the level of glucose synthesis required.

Question 60

How is the remaining energy needed during the mid phase of starvation obtained?

Answer 60

Muscle protein degradation begins to increase to around 75 g/day to provide amino acids that the liver can use as substrates for gluconeogenesis. Thus, muscle wasting starts after just a few days of fasting.

Question 61

The other adaptation that occurs during the mid phase of starvation is that glucagon stimulates _____ synthesis in liver. What is this used for?

Answer 61

Ketone body synthesis. Use as fuel in the brain.

Question 62

In the late phase of starvation, _____ in _____ continues to provide most of the body’s energy needs.

Answer 62

fat mobilization, adipose

Question 63

One adaptation that occurs during the late phase of starvation is that muscle protein degradation _____. Why is this? What does this cause?

Answer 63

Slows dramatically, in order to spare whatever muscle remains. This reduces substrate for gluconeogenesis in liver, and thus glucose production falls.

Question 64

How does rates of ketone body synthesis change in the late phase of starvation? How much of the brain’s energy supply comes from ketone bodies? What determines the length of this phase?

Answer 64

Increases further. 2/3rds. How long this phase lasts relies mainly on the size of the fat depot.

Question 65

The degradation of _____ also occurs during the late phase of starvation, which compromises cell functions throughout the body. What are the symptoms of this?

Answer 65

Non-muscle cellular protein. This produces many symptoms, the obvious ones being apathy, withdrawal, flaky skin, and susceptibility to infectious diseases.

Question 66

People usually die from _____ rather than directly from starvation.

Answer 66

an infectious disease

Question 67

Type 1 diabetes is referred to using these 2 terms. Describe the reasons for both.

Answer 67

Juvenile-onset diabetes since most of the time it is diagnosed in children or teenagers.

It is also referred to as insulin-dependent diabetes, due to the fact that individuals with this type of diabetes are deficient in insulin.

Question 68

Type 2 diabetes is also known as these 2 terms and is typically seen in these people.

Answer 68

Adult-onset diabetes or insulin-independent diabetes. This type of diabetes occurs in overweight and/or inactive adults, and at least in early stages presents no deficiency in insulin.

Question 69

What is the primary action of insulin? How does Type 1 diabetes affect this?

Answer 69

To stimulate glucose uptake and metabolism. All individuals with type 1 diabetes have elevated levels of blood glucose or hyperglycemia since the absence of insulin prevents glucose uptake into many organs and cells (brain is an exception to this). What this means is that despite there being lots of glucose in the blood of individuals with type 1 diabetes, many organs such as adipose, muscle and liver can’t use the glucose.

Question 70

While the blood is rich in glucose, the body of someone with type 1 diabetes is sending what signals?

Answer 70

That glucose is low, as if that person was fasting

Question 71

Insulin normally suppresses _____ release from the pancreas; this ensures that these two metabolically opposing hormones are not both secreted simultaneously. What occurs in Type 1 diabetics? How does this affect the body?

Answer 71

Glucagon. With insulin absent in type 1 diabetics, glucagon secretion becomes constitutively turned on all the time. This results in activation of gluconeogenesis and glycogenolysis in the liver, which only worsens the hyperglycemia. The signal for stimulation of gluconeogenesis results in muscle protein degradation to provide amino acids as substrates.

Question 72

In type I diabetics, glucagon also stimulates TAG hydrolysis in adipose, which floods the blood with fatty acids and glycerol. Because glucose uptake into adipose is dependent on insulin, what happens in these individuals? What does this result in?

Answer 72

Because glucose uptake into adipose is dependent upon insulin, the lack of glucose uptake results in a reduction in glycerol-3-P synthesis in adipose.

This results in the inability of adipose to replenish its fat depot.

Question 73

In muscle, the absence of insulin means that _____ glucose enters. What are the muscle glycogen levels and how much glucose is metabolized?

Answer 73

Very little, muscle glycogen is low and there is little glucose metabolized.

Question 74

Because muscle glycogen is low and there is little glucose metabolized in individuals with diabetes, how do the liver and muscle obtain energy? What does this result in? What condition can this cause?

Answer 74

Muscle and liver both actively oxidize fatty acids for energy. So much so, that levels of acetyl CoA become high, much of which is directed towards ketone body synthesis in liver, which is also stimulated by glucagon. The enhanced ketone body synthesis is consistent with the body sensing that there’s not sufficient glucose available, especially for the brain. The large increase in ketone bodies in the blood results in the most serious acute symptom of type 1 diabetes: ketoacidosis.

Question 75

Describe ketoacidosis. What is one of the major ketones produced, how is it excreted, and what does this present as?

Answer 75

The excess ketone bodies can produce a drop in pH of the blood to 6.8 or lower.

One of the ketones produced is acetone, which, because it is volatile, is gotten rid of through the lungs. This can be smelled on the breath of poorly managed diabetics and is often mistaken for intoxication.

Question 76

One major problem observed in diabetes that does not occur in starvation is excessive _____. Why does this occur? What happens as a result?

Answer 76

Urination. When blood glucose levels rise above a certain level, usually around 10 mM (twice normal), the kidney is unable to filter out all of the glucose in the blood. As a result, glucose starts appearing in the urine and gives it a sweet taste if you were to sample it.

Question 77

The glucose in urine creates an _____ which results in lots of water being excreted along with the glucose, increasing urine output. What condition does this excessive water loss lead to?

Answer 77

Osmotic pressure. This loss of water from the body leads to excessive thirst called polydipsia.