1)“Gluconeogenesis uses available energy and is therefore an energetically expensive process” why is gluconeogenesis necessary and under what conditions does it occur? What regulatory mechanisms ensure that glycolysis does not occur simultaneously with gluconeogenesis.

Gluconeogenesis is the process in which new glucose molecules are synthesized from non-carbohydrate sources, such as amino acids and glycerol, to maintain blood glucose levels. It is necessary because glucose is the primary energy source for certain tissues, such as the brain, that cannot rely solely on stored forms of glucose like glycogen.

Gluconeogenesis occurs in conditions where there is a high demand for glucose, but the dietary intake of carbohydrates is low or insufficient. This can happen during prolonged fasting, intense exercise, or in individuals following a low-carbohydrate diet. It also occurs in certain disease states such as diabetes or metabolic disorders.

To prevent simultaneous occurrence of glycolysis (the breakdown of glucose) and gluconeogenesis, the body has several regulatory mechanisms:

1. Substrate availability: To initiate gluconeogenesis, substrates like amino acids and glycerol need to be available. If there is a high concentration of carbohydrates in the diet, glycolysis will occur instead, as glucose is readily available.

2. Enzyme regulation: Key enzymes in the glycolysis and gluconeogenesis pathway are reciprocally regulated. For example, phosphofructokinase-1 (PFK-1) is an important enzyme in glycolysis and is inhibited by high levels of ATP and citrate, while fructose-1,6-bisphosphatase (FBPase-1), a key enzyme in gluconeogenesis, is activated by these same molecules.

3. Hormonal control: Hormones such as insulin and glucagon play a crucial role in regulating the balance between glycolysis and gluconeogenesis. Insulin promotes glycolysis and inhibits gluconeogenesis, while glucagon stimulates gluconeogenesis and inhibits glycolysis. These hormonal signals are influenced by blood glucose levels and other metabolic factors.

By coordinating substrate availability, regulating key enzymes, and exerting hormonal control, the body ensures that glycolysis and gluconeogenesis do not occur simultaneously, preventing wasteful energy expenditure and maintaining glucose homeostasis.