Metabolism

Question 1

____________ regulates the first of three highly-regulated IRREVERSIBLE glycolytic reactions

Answer 1

hexokinase

Question 2

______________ isozymes are allosteric enzymes and are inhibited by the reaction product, glucose 6-phosphate, such that as it accumulates, its further metabolism is reduced.

Answer 2

hexokinase

Question 3

where is glucokinase restricted to?

Answer 3

pancreas and beta cells

Question 4

___________ catalyzes an IRREVERSIBLE reaction, the ATP-dependent phosphorylation and trapping of
glucose in the cell.

Answer 4

Glucokinase (hexokinase iv)

Question 5

Why does glucokinase have a low affinity (high Km) for glucose?

Answer 5

low affinity for glucose ensures that when glucose is
plentiful it will be “trapped” and utilized by the liver, and when its intracellular concentration is low, it will not be recognized as a substrate.

Question 6

What does glucokinase’s high capacity (high vmax) mean?

Answer 6

higher capacity for glucose allows the liver to effectively remove the
high blood glucose concentrations that result from a carbohydrate-rich meal and prevents large amounts of
glucose from entering the systemic circulation, which minimizes the hyperglycemia that may result from such a meal.

Question 7

Is glucokinase subject to regulation by product inhibition?

Answer 7

Unlike hexokinase, NOOOO!

Question 8

__________ is the third enzyme in the glycolytic pathway, not only catalyzes the
rate-limiting, committed step of glycolysis, but also the second IRREVERSIBLE glycolytic reaction: fructose 6-
phosphate + ATP → fructose 1,6bisphosphate + ADP

Answer 8

6-Phosphofructo-1-kinase (PFK-1)

Question 9

________ is allosterically regulated by the energy charge of the cell

Answer 9

6-Phosphofructo-1-kinase (PFK-1)

Question 10

How is PFK-1 allosterically regulated by the energy charge of the cell?

Answer 10

Since the glycolytic process allows for the production of ATP, high concentrations of ATP inhibit the
enzyme, and, in contrast, high concentrations of AMP stimulate the enzyme

Question 11

what are the enzymes in irreversible steps of glycolysis?

Answer 11

1. hexokinase
2. PFK1
3. PK

Question 12

________ is allosterically inhibited by ATP, but is also similarly inhibited by alanine and long-chain
fatty acids, all of which will be plentiful during gluconeogenesis… ATP to drive the process and alanine as a required substrate

Answer 12

Pyruvate kinase (PK)

Question 13

Define what is meant by the energy charge and redox (reduction) potential of a cell.

Answer 13

1. Cytosol - ATP : AMP (adenylate cyclase)
2. Mitochondria - ATP: ADP
3. Redox potential - NADH : NAD+

Question 14

List the glucose-utilizing pathways that predominate in RBCs, brain, muscle, adipose and liver.

Answer 14

RBCs: anaerobic Glycolysis and pentose phosphate pathway in fed state

Brain tissue cells: pentose phosphate pathway, nucleotide synthesis, glycogen synthesis, and aerobic glycolysis, FA synthesis, TCA cycle

Heart and muscle cells: Fed state: responds to insulin, mobilizing GLUT 4 transporters from GSVs to their cell membrane. As insulin levels fall, GLUT 4 transporters are endocytosed and returned to GSVs via fusion w endosome (kept safe and inactive here). When the striated muscle cell floods with glucose (via glucose entry via GLUT 4), it will use 3 metabolic pathways

Question 15

List the four enzymes, and their intracellular location, for which pyruvate serves as a substrate, and the product that is made.

Answer 15

• Alanine aminotransferase
  
  • Lactate dehydrogenase
  • Pyruvate dehydrogenase
    Pyruvate Carboxylase

Question 16

List those tissues that respond to insulin vs. glucagon, and epinephrine.

Answer 16

• Cardiac and skeletal muscles (striated respond to insulin. When in fasting state, they respond to epinephrine to activate glycogen breakdown to release glucose as an energy source. Striated muscles DO NOT respond to glucagon!!
  
  • Adipose tissue cells are insulin-sensitive and use GLUT 4 for glucose entry in fed state. When in fasting state, will respond to epinephrine. DO NOT respond to glucagon but very sensitive to lack s of insulin

Liver is insulin-independent. When fasting level is reached, and insulin falls, glucagon levels rise. Glucagon binding to its receptors deactivates glycolysis and activates glycogenolysis

Question 17

Name the second messenger produced in response to glucagon-induced cellular signaling and how it functions to elicit the appropriate intracellular response.

Answer 17

• Protein Kinase A (PKA) is an effector that’s initiated as a result of being stimulated by glucagon or epinephrine when bound. Results in adenylate cyclase- conversion of ATP to cAMP.
  cAMP then activates kinase A by binding to its regulatory subunits