Metabolic Integration

Question 1

What are the 7 metabolic fuels that can be used to generate ATP and other biomolecules?

Answer 1

Glucose- derived from diet, Gluconeogenesis, and glycogen breakdown
Lactate- from anaerobic metabolism in muscle
Glycerol- from lipolysis of TAG in adipose
Fatty acids- from lipolysis of TAG in adipose, synthesis in liver
Ketone bodies- synthesized in liver
Amino acids- from diet and proteolysis of body proteins
Triacylglycerol- not really fuel itself but a source of fatty acids; transported in blood by lipoproteins

Question 2

What are the 3 potential types of stored fuel that can be accessed when needed and replenished when dietary sources become available?

Answer 2

Glycogen- carbohydrate and source of glucose (liver and muscle storage, muscle twice as large, storage limited by mass of muscle and liver)
Triacylglycerol- source of fatty acids stored primarily in adipose (little in liver, no limit to the amount of fat our bodies can store, no water required to store)
Protein- not a storage from of fuel under normal circumstances but can provide amino acids for use as glucose precursors in pathophysiological conditions (starvation and diabetes), used when glycogen and TAG levels are low
Table 14-1 page 3

Question 3

What is the livers role in metabolism?

Answer 3

All nutrients absorbed in small intestine enter into portal vein (flows directly to liver) so liver is positioned to be central metabolic organ
Produces fuel from nutrients from blood
Synthesizes glycogen from glucose so it can degrade it to glucose again when blood glucose levels drop (acts as glucose sensor)
Takes up lactate and alanine from muscle, and glycerol from adipose and converts them to glucose
After a meal, liver directs excess glucose toward glycogen synthesis and glycolysis, the Acetyl CoA from glycolysis is used to synthesize fatty acids

Question 4

What is the major fuel used by the liver to meet its own energy needs?

Answer 4

Fatty acids

Question 5

What happens in chronic elevation of glucose?

What happens if it falls too low?

Answer 5

Causes damage to endothelium of blood vessels and to nerves

Too low leads to weakness, dizziness, shaking, confusion, and coma

Question 6

What is the muscles role in metabolism?

Answer 6

Primary role of muscle is to contract, oxidation of a variety of fuels (glucose fatty acids ketone bodies) allows this to happen
At rest, muscles use fatty acids from blood
During exertion, muscles use glucose from blood and glycogen breakdown
During continuous exertion, lactate becomes a significant product in muscle (rates of glycolysis exceed TCA cycle)
Muscle protein is another potential source of energy (protein turnover releases amino acids) this is risky tho so not used a lot

Question 7

What is adipose’s role in metabolism?

Answer 7

Largest storage compartment for fuel in the body
Stores fatty acids as triaclyglycerol until needed for energy and release to blood
The fatty acids in triacylglycerol stored in an indictable can provide energy for several months without caloric intake

Question 8

Where does glucose 3P come from fro triacylglycerol synthesis in adipose?

Answer 8

It comes from the metabolism of glucose through glycolysis to dihydroxyacetone phosphate, which can be converted to glycerol 3P by glycerol phopshate dehydrogenase

Question 9

What is the brains role in metabolism?

Answer 9

Consumes 60% of all glucose utilized by the body and 15% of total energy needs
Under normal conditions, glucose is only fuel it uses to generate the large amount of ATP needed for nerve transmission
Requires constant supply of glycogen and oxygen from blood

Question 10

What are the big 3 hormones that influence metabolism?

Answer 10

Insulin
Glucagon
Epinephrine

Table 14-2 page 7

Question 11

What is insulin’s role in metabolism?

Answer 11

Produced and stored in pancreas, released into circulation in response to increase levels of glucose in blood (insulin signals fed state, triggers uptake of diet-supplied nutrients, replenishment of fuel depots, biosynthesis of macromolecules)
Stimulates glucose uptake into adipose and muscle (does this by translocation or movement of glucose transporters GLUT4 from intracellular sites to plasma membrane)
Insulin stimulates glycogen synthesis in liver and muscle by activating glycogen synthase and inhibiting glycogen phosphorylase
Insulin also stimulates glycolysis (increase activity of phopshofructokinase-1)

Question 12

What is glucagon role in metabolism?

Answer 12

Released by pancreases when blood glucose levels drop, targets liver and adipose, increases blood glucose levels so brain has adequate supply of its major fuel
Stimulates release of glucose from liver from glycogen Degradation and gluconeogenesis
Reduces use of glucose in liver as fuel so it can instead fo to blood
In adipose, glucagon stimulates fatty acid mobilization and release into the blood by stimulating hormone sensitive lipase

Question 13

What is epinephrines role in metabolism?

Answer 13

Fight or flight
Released from adrenal gland under stressful conditions that require energy
Works on liver, muscle, and adipose
Increases fuel availability and oxidation to produce ATP
I’m liver, it stimulates glycogen Degradation and inhibits glycogen synthesis
In muscle, it stimulates glycogen degradation and glycolysis (helps ATP production)
In adipose, it stimulates TAG hydrolysis (provides further fuel for muscle to use to form fatty acids)

Question 14

What is starvation?

Answer 14

Metabolic adaptation during a fast cannot be considered a single event (there are 3 phases)
Early phase (0-24 hours)
Mid phase (next 2-3 weeks)
Late phase (beyond week 3)

Question 15

What is the early phase of starvation and its effect of metabolism?

Answer 15

Glucose levels start dropping in blood, insulin levels drop but glucagon rises
Drop in insulin reduces glucose uptake and utilization by muscle, liver, and adipose so glucose can be used by brain
Glucagon stimulates gluconeogenesis and glycogen breakdown in the liver so the glucose release can maintain blood glucose levels
Glucagon stimulates TAG hydrolysis in adipose and those fatty acids are used by muscle, liver and other tissue as fuel

Question 16

What is the mid phase of starvation and its effect on metabolism?

Answer 16

Once liver glycogen is depleted, TAG hydrolysis in adipose continues at high rates, glycerol released from TAG hydrolysis is used by liver as substrate for gluconeogenesis
At this point (few days after fasting) when muscle protein degradation begins to in crease to around 75g/day to provide amino acids that liver can use as substrates for gluconeogenesis
Glucagon stimulates ketone body synthesis in liver (brain derives about a third of its energy from ketone bodies at this point)

Question 17

What is the late phase of starvation and its effect on metabolism?

Answer 17

Fat mobilization in adipose continues to provide most of body’s energy needs
Muscle protein degradation slows dramatically to spare whatever muscle remains, glucose production fails since no substrate for gluconeogenesis
Ketone body production increases further as the brain begins deriving more of its energy needs from ketone bodies (2/3 of energy needs)

Question 18

What is type 1 and type 2 diabetes?

Answer 18

Type 1- juvenile onset since its diagnosed in children or teenagers most. Individual with this are insulin deficient
Type 2- adult onset. This diabetes occurs in overweight and/or inactive adults usually, presents no deficiency of insulin

We focus on type 1 diabetes for metabolism as its easier to understand

Question 19

How does insulin and glucose work in type 1 diabetes?

Answer 19

Primary action of insulin is to stimulate glucose uptake, all individuals with type 1 diabetes have elevated levels of blood glucose since the absences of insulin prevents glucose uptake into many organs and cells
Despite being lots of glucose in the blood, people with type 1 diabetes’ organs like muscle and adipose cant use the glucose “starvation in the midst of plenty”
While the blood is rich in glucose, the body of someone with type 1 diabetes is sending signals that glucose is low, as if the person was fasting
Figure 14-1 page 10

Question 20

What happens to glucagon in type 1 diabetes people?

Answer 20

Insulin normally suppresses glucagon release from pancreas, with insulin absent in type1, glucagon secretion becomes turned on all the time
Results in activation of gluconeogenesis and glycogenolysis in the liver, which only worsens the hyperglycemia (elevated blood glucose)
Glucagon stimulates TAG hydrolysis in adipose, which floods the blood with fatty acids and glycerol
In muscle, the lack of insulin means very little glucose enters and thus muscle glycogen levels are low and there is little glucose metabolized
Muscle and liver oxidize fatty acids for energy

Question 21

What a re ketone bodies role in type 1 diabetes?

Answer 21

Levels of Acetyl CoA become high, much of which is directed towards ketone body synthesis in liver (also stimulated by glucagon)
Large increase in ketone bodies in the blood results in most serious acute symptom of type 1: ketoacidosis
Excess ketone bodies produce a drop in pH in blood to 6.8 or lower
One of ketones produced is acetone, and is excreted through lungs which smells like alcohol

Question 22

Why do you urinate more with diabetes?

Answer 22

When blood glucose levels rise above a creation level, 10mM (twice normal), the kidneys are unable to filter out all of the excess glucose in the blood. As a result, glucose starts appearing in the urine and gives it a sweet taste if your ere to sample it
Glucose in urine creates an osmotic pressure which results in lots of water being excreted along with the glucose