1) The two pathways - Gluconeogenesis and Glycolysis, are reciprocally regulated in liver cells, meaning only one pathway is active at a time. Briefly describe the goal of each of these pathways. Then explain the importance of regulating these two pathways in this way. 2) One way that insulin signaling regulates metabolism is by activating an enzyme that produces an allosteric regulator of Phosphofructokinase (PFK). Explain the role and importance of PFK in metabolism. Then predict whether allosteric regulation induced by insulin will activate or repress PFK activity. 3) PFK is inhibited when ATP and citrate (an intermediate in the TCA cycle) are abundant inside the cell. Explain the metabolic connection between high [ATP] and high [citrate] (i.e. how does one affect the other?). Then explain the metabolic logic of using these molecules to inhibit PFK

1) gluconeogenesis and glycolysis

goal of gluconeogenesis pathway

Gluconeogenesis is not the reversal of the glycolysis, but the generation of glucose from non-carbohydrate precursors (like odd chain fatty acids and proteins).

The reason or the goal why we have this process is because some organs and tissues can only use glucose as their energy source hence the need for formation of glucose

These include the brain (although ketone bodies can be used here as well), erythrocytes, testes and the kidney medulla.

Usually the glucose for the supply of these tissues comes directly from carbohydrates in food or storage carbohydrates as glycogen or starch, but when these are not available, the body has another way to get around this problem and to avoid the starvation of these tissues goal for glycolysis

Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism.

The main purpose of glycolysis is to provide pyruvate for the trichloroacetic acid ( TCA) cycle, not to make adenosine 5′-triphosphate

importance

Gluconeogenesis and glycolysis are coordinated so that within a cell one pathway is relatively inactive while the other is highly active

They help prevent  hydrolysis of four nucleotide triphosphates (two ATP plus two GTP) per reaction cycle.

They also help in controlling inhibition of pyruvate kinase by phosphorylation during starvation.

2)role and importance of phosphofructokinase in metabolism

role

it is responsible for catalyzing the primary regulatory step in glycolysis: the phosphorylation of fructose 6-phosphate to fructose 1,6-biphosphate by ATP. 

Phosphofructokinase plays an important catalytic role in transient glycolysis that enables mitochondrial fusion and the stimulation of the S phase entry

importance

has an importance in mutation and cancer: In order for cancer cells to meet their energy requirements due to their rapid cell growth and division, they survive more effectively when they have a hyperactive phosphofructokinase 1 enzyme

effects of insulin on phosphofructokinase activity

induction of insulin activates the PFK activity

 the association of phosphofructokinase and F-actin can be affected by insulin stimulation in rabbit skeletal muscle homogenates and that this association can be a mechanism of phosphofructokinase regulation.

 The presence of F-actin increases the affinity of phosphofructokinase for fructose 6-phosphate

3) metabolic connection between high ATP and high citrate

The interconversion of fructose 6-phosphate and fructose 1,6-bisphosphate is stringently controlled .  AMP stimulates phosphofructokinase, whereas ATP and citrate inhibit it. Fructose 1,6-bisphosphatase, on the other hand, is inhibited by AMP and activated by citrate. A high level of AMP indicates that the energy charge is low and signals the need for ATP generation. Conversely, high levels of ATP and citrate indicate that the energy charge is high and that biosynthetic intermediates are abundant

metabolic logic of using them to inhibit PFK

PFK is regulated by ATP, an ADP derivative called AMP, and citrate, as well as some other molecules 

ATP is a negative regulator of PFK, which makes sense: if there is already plenty of ATP in the cell, glycolysis does not need to make more

Citrate, the first product of the citric acid cycle, can also inhibit PFK. If citrate builds up, this is a sign that glycolysis can slow down, because the citric acid cycle is backed up and doesn't need more fuel