General Metabolism Review

Question 1

What GLUT is expressed in the liver and beta-islet cells and why is this beneficial?

Answer 1

GLUT2 - which has a high Km and a low affinity. The liver really only wants to store glucose where there is excess available. GLUT is also bidirectional and glucose can leave through this if needed. This is important because of the breakdown of glucose.

Question 2

What GLUT is expressed in muscle and why is this beneficial?

Answer 2

GLUT4 is expressed in the muscle, it will only absorb glucose in the presence of insulin.

Question 3

What GLUT is expressed in the brain and why is this beneficial?

Answer 3

GLUT3 is expressed in the brain. It has a low Km meaning it has a high affinity. This is because the brain needs to be the primary receiver of glucose

Question 4

What enzyme carries out the first step of glucose metabolism in liver and pancreatic cells and why is it beneficial?

Answer 4

Glucokinase, it has a high Km meaning low affinity. This is because only at high concentrations will glucose get trapped in the liver. If glucose is at low concentrations, it will have to leave the liver. It also has a high Vmax so it can handle the increased work load if needed.

Question 5

What enzyme carries out the first step of glucose metabolism in tissues other than the liver and pancreas and why is it beneficial?

Answer 5

Hexokinase, it has a low Km meaning high affinity. It has a decreased Vmax, because they are not meaning to have large amounts of glucose like the liver. It also experiences feedback inhibition by G-6-P

Question 6

What is the overall net reaction of glycolysis?

Answer 6

1 glucose + 2 NAD+ is going to yield 2 pyruvate, 2 NADH, and 2 ATP

Question 7

Low or no O2 will lead the pyruvate from glycolysis to undergo what? Why does this happen

Answer 7

Pyruvate + NADH will yield lactate via lactate dehydrogenase. This is due to the need to keep up NAD+ levels in order to keep glycolysis going

Question 8

In condition of adequate O2 what are the fates of pyruvate from glycolysis?

Answer 8

It can from Acetyl-CoA via the pyruvate dehydrogenase complex
Form oxaloacetate via pyruvate decarboxylase (biotin req)
Form alanine via alanine aminotransferase

Question 9

What can be the result of a pyruvate dehydrogenase complex deficiency?

Answer 9

Back up of pyruvate and alanine. Leads to lactic acidosis. This can be shown by an increase in ketogenic nutrients

Question 10

What is a probable fate for the lactic acid produced during low O2 conditions?

Answer 10

It will be taken up by the liver and converted back into pyruvate then back into glucose (Cori Cycle) b/c liver is the major site for gluconeogenesis

Question 11

What are the possible fates for oxaloacetate that is produced from pyruvate?

Answer 11

It can be used to fuel the TCA cycle by reacting with Acetyl CoA to form citrate = 1st step in TCA cycle.
Pyruvate to oxaloacetate is also the 1st step in gluconeogenesis.

Question 12

What are the possible fates for acetyl CoA produced from pyruvate?

Answer 12

Can enter the TCA cycle to react with oxaloacetate.

It can also provide the building blocks for ketone bodies acetoacetate and beta-hydroxybutyrate

Question 13

What is the overall net reaction of the TCA cycle?

Answer 13

Citrate (6 carbon) yields (4 carbon) oxaloacetate, two CO2, 3 NADH, 1 FADH2, and 1 GTP

Question 14

What is the rate limiting enzyme in glycogen synthesis and what is it regulated by?

Answer 14

The enzyme is glycogen synthase. It is positively regulated by glucose and insulin. It is negatively regulated by epinephrine and glucagon

Question 15

During fasting where does glucose come from?

Answer 15

Glycogenolysis

Question 16

What is the rate limiting enzyme in glycogenolysis and what is it regulated by?

Answer 16

Glycogen phosphorylase. It is positively regulated by AMP, epinephrine, and glucagon. It is negatively regulated by ATP and insulin

Question 17

What are the 4 key enzymes in gluconeogenesis and what is the rate limiting enzyme?

Answer 17

Fructose-1,6-BPase is the rate limiting enzyme and it catalyzes that reaction of F-1,6-BP to F-6-P

Pyruvate carboxylase catalyzes the reaction of pyruvate to oxaloacetate

PEP Carboxykinase catalyzes the reaction of oxaloacetate to PEP

Glucose-6-phosphatase catalyzes the reaction of G-6-P to glucose

Question 18

What is the rate limiting step for fatty acid synthesis and how is it regulated?

Answer 18

The enzyme acetyl-CoA carboxylase is positively regulated by insulin and citrate, and negatively regulated by glucagon

Question 19

What is the rate limiting step for oxidation of fatty acids and what is it regulated by?

Answer 19

Carnitine Transferase is regulated by malonyl-CoA

Question 20

What are the main enzymatic differences between the liver and the muscle/brain?

Answer 20

Liver contains G-6-Pase and the muscle and brain do not. Meaning the muscle and brain cannot release glucose. Liver also does not contain the enzymes needed to utilize ketone bodies, which the brain can use them

Question 21

What would be a consequence of blocking G-6-Pase in the liver?

Answer 21

This would block the export of glucose in the liver leading to abnormally high glycogen levels and low blood glucose levels

Question 22

What would be a consequence of blocking the PFK-2?

Answer 22

It would lead to a decrease in F-2,6-BP which would lead to a decrease in the function of PFK and sub sequentially lower rate of glycolysis

Question 23

Why would an experienced runner not take a bunch of sugar before a long marathon?

Answer 23

High blood sugar levels would trigger the release of insulin which would stimulate the synthesis of glycogen. High insulin level would impede the mobilization of energy reserves.

Question 24

Glucagon signifies a starved state yet it inhibits glycolysis in the liver why might this be?

Answer 24

A role of the liver is to provide glucose for other tissues. In the liver, glycolysis is used not for energy production but for biosynthetic purposes. Consequently, in the presence of glucagon, liver glycolysis stops so that the glucose can be released into the blood.