Metabolic Integration - RS

Question 1

As a general rule synthesis and degradation don’t occur simultaneous, how do the cells ensure this?

Answer 1

Through reciprocal regulation. Agents that promote catabolis (breakdown/ energy mobilization) inhibit anabolism (synthesis, storage of energy) and vice-versa.

Question 2

Can Acetyl CoA form glucose?

Answer 2

No. If energy is needed it will go to make ketone bodies. Even though OAA can be converted to glucose there can be no net conversion of acetyl-CoA to glucose.

Question 3

What is true of the glycerol backbone of TG during the prolonged fasting state?

Answer 3

The 3 C of the glycerol backbone of TG can be used to synthesize glucose under conditions of prolonged fasting (when lipolysis is the major source of energy)

Question 4

What is an exception of FA that can be converted to glucose?

Answer 4

Oxidation of odd-chain FA produces propionyl-CoA which can be converted to glucose.

Question 5

TCA intermediates are bled off into various biosynthetic pathways. What does each go to: Citrate, a-ketoglutarate, succinyl CoA, malate, oxaloacetate?

Answer 5

Citrate - Fatty acid synthesis
a-ketoglutarate - Amino acid synthesis (& neurotransmitter)
succinyl CoA - Heme synthesis
malate - gluconeogenesis
oxaloacetate - Amino acid synthesis

Question 6

What is the carbon source for the anaplerotic reactions (metabolism reactions)?

Answer 6

Pyruvate (derived from glucose, from certain glucogenic amino acids, or from cytosolic OAA via malate dehydrogenase and malic enzyme- but not to any significant extent from fat). Carbohydrate is even needed to break down fat (conversion of pyruvate to OAA). It’s also needed to store fat.

Question 7

What is the general rule for what catabolic and energy mobilizing enzymes?

Answer 7

They are active when phosphorylated. Glycogen phosphorylase, phosphorylase kinase, hormone-sensitive lipase.

Question 8

What is the general rule for what anabolic enzymes are active?

Answer 8

They are inactive when phosphorylated. Acetyl-CoA carboxylase, glycogen synthase, HMG-CoA reductase.

Question 9

What is insulin a signal for? Does it promote phosphorylation or dephosphorylation?

Answer 9

It is a signal for high blood glucose levels. It is the anabolic signal and thus promotes dephosphorylation.

Question 10

What is glucagon a signal for? Does it promote phosphorylation or dephosphorylation?

Answer 10

Signal for low blood glucose levels. It is a catabolic enzyme. It increases phosphorylation of key enzymes by activating a cAMP-dependent protein kinase, PKA

Question 11

What is epinephrine a signal for? Does it promote phosphorylation or dephosphorylation?

Answer 11

Signal that energy is needed right away. It is catabolic and stimulates breakdown of glycogen, fat, and protein. It increases phosphorylation of key enzymes by activating a cAMP-dependent protein kinase, PKA

Question 12

What is the exception to the rule about avoiding futile cycles?

Answer 12

When the body has low blood glucose conditions, so low insulin and high counter-regulatory hormones (glucagon, cortisol, catecholamines). Under these conditions cAMP levels in adipocytes are elevated, leading to lipolysis, but also to the expression of PEPCK and the formation of glycerol for glyceroneogenesis. A significant amount of NEFA generated are re-esterified instead of being released into the circulation.

Question 13

Page 420

Answer 13

Chill. Also great chart.

Question 14

Describe what happens in the body in the fed state?

Answer 14

Anabolic processes are favored

Question 15

Knowing which biochemical pathways operate in each tissue is a key to understanding metabolic integration.

Answer 15

Look on page 422 for some great charts.

Question 16

Which blood fuel is in highest concentration? Which has the highest turnover rate?

Answer 16

Glucose, there is about 20g in the blood of glucose or 80 calories. There is .3g of fat or 3 cal, however FA are the major fuel in the human. 540 calories are used in a 12-hour period from FA, while 280 are used from glucose. 540/3 is a turnover of 180 per 12-hr. 280/80 is a 3.5 turnover per 12-hr. The glucose is not used and replaced as rapidly as the FA. The glucose does not turn over as rapidly as the FA.

Question 17

What happens in the basal state?

Answer 17

This is a brief fast, mostly just overnight (12-hr fast). Low energy levels lead to increased glycolysis in most tissues. Hormonal responses to low glucose levels turn on lipolysis in fat cells, proteolysis in muscle, and gluconeogenesis in the liver.

Question 18

Page 427 and 428

Answer 18

Huge diagram, great summary

Question 19

What happens to the plasma levels of glucose, ketone bodies, and fatty acids during starvation?

Answer 19

Glucose goes down at first but levels off. Ketone bodies rise dramatically. Fatty acids rise very slowly.

Question 20

There is a decrease in urea excretion after prolonged fasting, why?

Answer 20

It reflect decreased breakdown of muscle protein. After 3-5 days the brain’s energy needs are met by KB. Gluconeogenesis decreases, sparing muscle and other tissues.

Question 21

What is ketoacidosis?

Answer 21

It is the presence of excess KB in the blood which occurse when the ability of the idneys to excrete KB is exceeded, producing a metabolic acidosis because the buildup of acetoacetic and B-hydroxybutyric acids exceeds the buffering capacity of the plasma. (this happens most often in people with uncontrolled type I diabetes)

Question 22

Compare and contrast starvation and diabetes (starvation on this side)

• Low insulin/ glucagon ratio, but some insulin always present
• Moderately high rate of lipolysis in fat cells
• Moderate production of KB by liver
• Metabolic adjustments are gradual and manageable: gradual shift in use of KB as fuel by various extrahepatic tissues. any excess in KB in blood can be excreted.
• No ketacidosis

Answer 22

• Zero circulating insulin
• Uninhibited, maximal lipolysis in fat cells
• maximal production of KB by liver
• KB production overwhelms KB removal. Metabolism in extrahepatic tissues, excretion by kidneys, exhalation of acetone
• increase KB in blood, causing metabolic acidosis

Question 23

What does epinephrine do?

Answer 23

stimulates glycogen breakdown in muscle and liver, gluconeogenesis in liver, and lipolysis in adipose tissue.

Question 24

What do glucocorticoids do?

Answer 24

Stimulate lipolysis in adipose tissue and the release of AA from muscle protein. In liver, glucocorticoids stimulate gluconeogenesis and stimulate the synthesis of glycogen.