Glycogen Phosphorylase (GP) Regulation + Hemoglobin and Myoglobin

What reaction does glycogen phosphorylase catalyze?

Cleaves glucose units from nonreducing ends of glycogen via phosphorolysis → glucose-1-phosphate.

What cofactor does GP use?

Pyridoxal 5′-phosphate (PLP), acts as an acid-base catalyst.

GP is ____ly and _____ly regulated

covalently; allosterically

What is the structure of glycogen phosphorylase?

Dimer (842 residues per subunit), each with active site, allosteric site, and phosphorylation site at Ser14.

What allosterically converts GP between R (active) and T(inactive) forms?

AMP is an activator T(Inact) → R (act), while ATP and glucose-6-p are inhibitors R(act) → T (inactive).

What happens when energy is low? GP

AMP binds → enzyme activated → glycogen breakdown increases.

How is GP covalently activated?

Phosphorylation by phosphorylase kinase converts GP-b (inactive) → GP-a (active).

What hormones trigger GO covalent modification?

glucagon and epinephrine (adrenaline)

What is the role of myoglobin? Oxygen ___ in muscles; ___mer with one heme group; __ O₂-binding curve.

storage ; mono; hyperbolic

What is the role of hemoglobin? oxygen ___ in blood; ___mer (α₂β₂); ___ O₂-binding curve (cooperative).

transport ; tetra; sigmoidal

How does Hb exhibit cooperativity?

Binding of one O₂ increases affinity of remaining subunits (T→R transition).

What causes the sigmoidal shape of the Hb binding curve?

Cooperative O₂ binding between Hb subunits.

What is the Bohr Effect?

At low pH (high [H⁺] and CO₂), Hb’s O₂ affinity decreases, enhancing O₂ release to tissues.

Does myoglobin show the Bohr effect?

No, Mb’s O₂ binding is unaffected by pH.

What is 2,3-BPG and what does it do?

A glycolysis byproduct that binds between Hb’s β-subunits, stabilizing T-state and decreasing O₂ affinity, releasing O2.

Why does fetal Hb bind O₂ tighter? What is the physiological importance?

A: Fetal Hb (α₂γ₂) has Ser instead of His at position 143 → weaker BPG binding → higher O₂ affinity. Allows fetus to extract oxygen from maternal blood.

What causes sickle-cell anemia?

Point mutation: Glu → Val at β-chain position 6 (HbS).

What effect does the sickle cell mutation have?

HbS polymerizes under low O₂ → RBCs deform/shrivel → block capillaries → cause anemia.

What metal is central to the heme group, and what is its oxidation state?

Fe²⁺ (ferrous iron) — coordinates 6 ligands (4 from porphyrin, 1 from His F8, 1 from O₂)

What local structure change happens to the iron atom when O₂ binds in Hb?

It moves into the plane of the porphyrin ring and drags His F8 along, triggering conformational change

What global structural change enables Hb cooperativity?

Movement of one αβ pair by ~15° relative to the other, breaking salt bridges, and improving O2 binding

What happens when CO₂ binds to Hb?

Forms carbamates on amino termini, stabilizing T-state and promoting O₂ release

Phosphofructokinase 1 (PFK 1) role and how is it controlled

commits glucose to glycolysis by forming fructose 1,6
bisphosphate. allosterically regulated.

PFK1 inhibitor

ATP and citrate

PFK1 activator

MP, ADP, fructose 2,6 bisphosphate

Aspartate Transcarbamoylase (ATCase) role and how is it controlled

first committed step of pyrimidine synthesis, Activity controlled by allosteric regulation and cooperativity

ATCase inhibitor

CTP (end-product)

ATCase activator

ATP

How many heme (containing Fe) groups are in Hb vs Mb

Hb: 4

Mb: 1

Hb function- what does it transport?

Transports oxygen from lungs to tissues and carries CO₂ back to the lungs for exhalation