## **Core Concept**
The regulation of enzymes by phosphorylation is a key post-translational modification that can either activate or inhibit enzyme activity. This process involves the addition of a phosphate group to specific amino acid residues on the enzyme, typically serine, threonine, or tyrosine, which can alter the enzyme's conformation and thereby its activity. Phosphorylation is a reversible modification, allowing for dynamic regulation of metabolic pathways.

## **Why the Correct Answer is Right**
Glycogen synthase is an enzyme involved in glycogen synthesis. It exists in two forms: an inactive form (glycogen synthase D) and an active form (glycogen synthase I). The conversion between these forms is regulated by phosphorylation and dephosphorylation. When glycogen synthase is phosphorylated, it is in its less active form. Therefore, glycogen synthase is indeed regulated by phosphorylation.

## **Why Each Wrong Option is Incorrect**
- **Option A:** Pyruvate kinase is an enzyme that catalyzes the final step of glycolysis, converting phosphoenolpyruvate (PEP) into pyruvate, generating one molecule of ATP per converted molecule. Pyruvate kinase is regulated by phosphorylation. When phosphorylated, pyruvate kinase is less active, which inhibits glycolysis. This makes option A an example of an enzyme regulated by phosphorylation, not the correct answer to "all except."

- **Option B:** Phosphofructokinase-2 (PFK-2) is an enzyme that plays a critical role in the regulation of glycolysis and gluconeogenesis by producing fructose-2,6-bisphosphate (F-2,6-BP), a potent activator of phosphofructokinase-1 (PFK-1), a key enzyme in glycolysis. PFK-2 activity is regulated by phosphorylation. This indicates that option B is also an example of an enzyme regulated by phosphorylation.

- **Option C (Correct Answer):**
- **Option C:** Inactive **dephospho form** or more accurately not requiring regulation by phosphorylation for its activity, **Glycogen phosphorylase kinase** actually gets activated by phosphorylation but directly acts on **glycogen phosphorylase** (an enzyme critical for glycogen breakdown) which then gets activated. However **PFK-1** gets inhibited by this mechanism through PFK-2 product decrease.

## **Clinical Pearl / High-Yield Fact**
A memorable point for exams is that the regulation of metabolic pathways by phosphorylation/dephosphorylation is crucial for cellular responses to external signals, such as hormones. For instance, in diabetes, understanding the regulation of key enzymes in glucose metabolism by phosphorylation can provide insights into the disease's pathophysiology and treatment.

## **Correct Answer:** . Inactive dephospho form.