Integrated Metabolism

Question 1

Since ATP is at the center of metabolism, what is the difference between anabolic metabolic process and catabolic oxidation process?

Answer 1

Catabolic leads to the production and release of ATP

Anabolic processes consumes ATP

Question 2

What are the key metabolites and what junction do they meet at?

Answer 2

Amino acids, glucose and glycerol+fatty acids; meet at pyruvate

Question 3

Where do key metabolites come from?

Answer 3

protein, carbohydrates and fat (dietary intake)

Question 4

What are the excretory waste products produced from key metabolites?

Answer 4

Urea from Amino acids and water/carbon dioxide from citric acid cycle

Question 5

There must be a balance of catabolism vs. anabolism in the body. What can the body do with blood glucose?

Answer 5

Use it, store it or convert it

Question 6

What are the key metabolic players?

Answer 6

glucose-6-phosphate, pyruvate and acetyl-CoA

Question 7

What main metabolic pathways use Glucose-6-phosphate?

Answer 7

glyconeogenesis, glycogenolysis, glycolysis and pentose phosphate pathway

Question 8

Which metabolite has a negative allosteric effect on phosphofructokinase-1?

Answer 8

ATP; high concentrations will inhibit

Question 9

What will happen to G6-P if phosphofructosekinase-1 is inhibited?

Answer 9

Concentration will increase

Question 10

What enzyme will be stimulated at high levels of G6-P? What enzyme will be inhibited?

Answer 10

glycogen synthase leading to the formation of glycogen

inhibits glycogen phosphorylase thereby inhibiting glycogenolysis (glycogen degradation)

Question 11

When there are high levels of NADP+ and low levels of NADPH, what does G6-P do?

Answer 11

It is used in the pentose phosphate pathway to produce NADPH

Question 12

When there are low levels of NADP+ and high levels of NADPH, what does G6-P do?

Answer 12

PPP will not operate regardless of the concrentration of G6-P

Question 13

How do the two isomers, Fructose-2,6-bisphosphate and Fructose-1,6-bisphosphate interact?

Answer 13

Abundance of F-1,6,-BP leads to a higher concentration of F-2,6-BP which in turn stimulates phosphofructokinase-1 ; this is known as feed forward stimulation

Question 14

When there are high levels of glucose in the body, what hormone control is implemented and what is the result?

Answer 14

beta cells in the pancreas release insulin

decrease glucagon by increasing glycogen synthase and decreasing glycogen phosphorylase activity

Question 15

When there are low levels of glucose in the body, what hormone control is implemented and what is the result?

Answer 15

pancreas releases glucagon–>liver G-protein–>cAMP–>phosphorylates glycogen synthase (no glycogen synthesis) and dephosphorylates glycogen phosphorylase (glycogenolysis)

Question 16

What is the second major branch point in metabolism?

Answer 16

pyruvate

Question 17

In low levels of energy (NADH not ATP) what enzyme is inhibited and how does it effect pyruvate?

Answer 17

pyruvate dehydrogenase kinase (PDK) is inhibited which keeps pyruvate dehydrogenase active. Leads to pyruvate is oxidatively decarboxylated to acetyl-CoA

Question 18

What happens to pyruvate when there is high levels of NADH and Acetyl-CoA?

Answer 18

pyruvate dehydrogenase kinase is activated (turns off pyruvate dehydrogenase and Citric Acid Cycle)

Question 19

If you have high concentration of ATP and Acetyl-CoA what happens to pyruvate carboxylase?

Answer 19

Pyruvate carboxylase is stimulated which is the first step of gluconeogensis as alternative pathway

Question 20

How does pyruvate play a role in skeletal muscles if delta G is negative? What is the reaction and product and is it favorable?

Answer 20

In low levels of oxygen and anaerobic respiration, pyruvate combines with NADH and Hydrogen ion by the enzyme lactate dehydrogenase to produce lactate or lactic acid. The reaction is favorable since delta G is negative

Question 21

How is lactate dehydrogenase stimulated under anaerobic conditions?

Answer 21

high levels of NADH

Question 22

What is the Cori Cycle? (aka Lactic Acid Cycle)

Answer 22

in the liver, lactate can be converted back to glucose for energy production

Question 23

What happens when there is a high concentration of lactic acid buildup in skeletal muscle and what is the signal?

Answer 23

inhibition blocks further conversion of pyruvate to lactate; burning sensation in muscles sends the signal

Question 24

In the muscle, what enzyme converts pyruvate to alanine?

Answer 24

Alanine transaminase

Question 25

What is the Alanine Cycle?

Answer 25

converts alanine back to pyruvate and glucose (gluconeogenesis) in the LIVER

Question 26

Once oxygen levels are restored in skeletal muscles, what can resume?

Answer 26

ATP production via CAC/oxidative phosphorylation

Question 27

What is the third primary branch point of metabolic control?

Answer 27

Acetyl-CoA

Question 28

When there is too much energy, (high NADH/NAD+ ratio), what happens?

Answer 28

NADH inhibits the CAC via isocitrate dehydrogenase and alpha ketglutarate dehydrogenase FADH2 causes increase in succinyl-CoA that slows down the CAC

Question 29

In a fed state, how can the liver use acetyl-CoA?

Answer 29

make cholesterol, and/or Fatty acids / tricyglycerols; increase in oxaloacetate condenses with acetyl-CoA producing citrate; increased citrate is transported to cytoplasm for FA synthesis and activates acetyl-CoA carboxylase and inhibits phosphofructokinase-1 (blocks glycolysis); G6-P that is blocked from glycolysis can be used to make glycogen or sent to PPP for make NADPH for FA synthesis

Question 30

During starvation, what happens to acetyl-CoA?

Answer 30

FA oxidation supplies energy for gluconeogenesis; increase in acetyl-CoA from oxidation of FA stimulates pyruvate carboxylase to promote gluconeogenesis

Question 31

What does low levels of citrate and ATP/NADH/FADH2 promote?

Answer 31

Active CAC and oxidative phosphorylation

Question 32

Which hormones stimulate glucose production in the liver when blood glucose is low and which hormones inhibit glucose use in muscle and adipose tissue?

Answer 32

Glucagon, catecholamines, cortisol and growth hormone stimulate liver Cortisol and growth hormone inhibit glucose use

Question 33

Which hormone inhibits liver glucose production and stimulates glucose use in muscle and adipose tissue when blood glucose levels are high?

Answer 33

Insulin

Question 34

What is the process to form active insulin?

Answer 34

Prepoinsulin leader sequence removed forming proinsulin. Cleavage of the C-peptide will produce the the active form of insulin

Question 35

If there is any metabolic pathway that produces glucose, how will insulin effect it?

Answer 35

Insulin will not stimulate any metabolic pathway that produces glucose or carbohydrate.

Question 36

What is the process of insulin being released from Beta Cells in the pancreas when glucose levels are high?

Answer 36

Glucose enters the beta cells via the glucose transporter 2 (passive transport) Glucose oxidation increases ATP levels and stimulated potassium channels Depolarization opens voltage gated calcium channels to be released from the endoplasmic reticulum Increase of intercellular calcium levels triggers release of insulin

Question 37

Glucagon is a hormone that is released from alpha cells in the pancreas when glucose levels are low. What does the release of glucagon stimulate?

Answer 37

Acts mainly on liver stimulating glycogenolysis, gluconeogenesis, and FA oxidation Glucagon can also stimulate the release of insulin allowing insulin-sensitive cells to take up the released glucose

Question 38

Define catecholamines? What are they duel-hatted as?

Answer 38

They can acts as a neurotransmitter or hormone depending on the body's needs They are hormones (norepinephrine and epinephrine) that can provide immediate regulation of metabolism. Stimulates glycogenolysis and glycolysis for production of ATP in the muscle and inhibit glycolysis in the liver to provide glucose for the blood

Question 39

Which metabolic pathways and location are stimulated by insulin?

Answer 39

Liver (gluconeogenesis, glycogenolysis) Adipose tissue (Lipolysis) Skeletal Muscle (glycolysis, glycogenolysis, and triglyceride uptake from lipoproteins)

Question 40

What is Cortisol and what does it stimulate?

Answer 40

Cortisol is a chronic stress hormone that regulates metabolism Stimulates corticotropin-releasing factor and adrenocorticotropic hormone. Released from the adrenal glands

Question 41

What is Diabetes Mellitus Type I?

Answer 41

No insulin is made at all (usually skinny people) Result of autoimmune destruction of beta cells which leads to loss of insulin production Without insulin, gluconeogenesis runs wild increasing blood glucose levels. Muscle and fat cells cannot take up available blood glucose via GLUT4 and the body can't clear the elevated levels Leads to increase lipolysis which increases ketone bodies (toxic) which leads to KETOACIDOSIS

Question 42

What is Diabetes Mellitus Type II?

Answer 42

Insulin is produced but tissues are resistant to its effects (usually in fat people) Results in uncontrolled gluconeogenesis which increases blood glucose levels even with high amount of insulin present Ketoacidosis is not common Leads to hyperosmolar hyperglycemia nonketotic syndrome (body tries to get rid of excess sugar by passing it into the urine)