Chapter 21: Glycogen Metabolism

Comprehensive vocabulary flashcards covering the enzymes, regulatory mechanisms, hormone pathways, structural features, and intermediate species of glycogen breakdown and synthesis.

Glycogenin

A core priming protein located at the center of each glycogen particle that initiates glycogen synthesis by covalently attaching the initial glucose residue to a specific tyrosine hydroxyl (-OH) group.

Phosphorolysis

The cleavage of a covalent bond by the addition of inorganic phosphate ($P_i$), which serves as the attacking nucleophile to yield a phosphorylated sugar without expending ATP.

Glycogen phosphorylase

A dimeric enzyme composed of two identical 842-residue subunits that catalyzes the phosphorolytic cleavage of glucose residues from nonreducing ends of glycogen to produce glucose 1-phosphate.

Pyridoxal phosphate (PLP)

A vitamin $B_6$-derived cofactor covalently bound via a Schiff-base linkage to a lysine residue in glycogen phosphorylase, where its phosphate group acts in general acid-base catalysis.

Schiff-base linkage

A covalent imine linkage ($\text{-CH=N-}$) formed between the aldehyde carbonyl of pyridoxal phosphate (PLP) and the $\epsilon$-amino group of a lysine residue in glycogen phosphorylase.

Tower helix

A structural motif comprising residues 262 to 278 in each subunit of glycogen phosphorylase that extends into the subunit-subunit interface and packs against the corresponding helix of the opposite subunit.

Phosphoglucomutase

An enzyme that catalyzes the reversible interconversion of glucose 1-phosphate and glucose 6-phosphate via a glucose 1,6-bisphosphate intermediate utilizing a catalytic phosphoserine residue.

Monod-Wyman-Changeux (MWC) model

The allosteric concerted model describing glycogen phosphorylase equilibrium between an active relaxed (R) state and an inactive tense (T) state, regulated by effector molecules.

Phosphorylase b

The unphosphorylated, typically inactive (T state) form of glycogen phosphorylase that can be allosterically activated by high concentrations of AMP and inhibited by ATP and glucose-6-phosphate.

Phosphorylase a

The phosphorylated, fully active (R state) form of glycogen phosphorylase produced when Ser14 on each subunit is phosphorylated by phosphorylase kinase.

Phosphorylase kinase

A regulatory kinase activated by Protein Kinase A phosphorylation and $\text{Ca}^{2+}$ binding that converts inactive phosphorylase $b$ into active phosphorylase $a$.

Phosphoprotein phosphatase 1 (PP1)

A phosphatase that reverses regulatory phosphorylation events by inactivating glycogen phosphorylase and phosphorylase kinase while simultaneously activating glycogen synthase.

Debranching enzyme

A bifunctional enzyme with transferase activity (shifting three glucose residues from a branch to a nearby chain) and $\alpha\text{-(1}\rightarrow\text{6)}$-glucosidase activity (hydrolyzing the remaining single branch residue to yield free glucose).

UDP-glucose pyrophosphorylase

An enzyme that activates glucose by catalyzing the phosphoanhydride exchange between glucose 1-phosphate and UTP to generate UDP-glucose and pyrophosphate ($PP_i$).

UDP-glucose

An activated nucleotide sugar that serves as the immediate glucosyl donor for the elongation of glycogen chains during glycogen synthesis.

Glycogen synthase

The key regulatory enzyme of glycogen synthesis that transfers glucosyl residues from UDP-glucose to the C-4 hydroxyl group at the nonreducing ends of glycogen, forming $\alpha\text{-(1}\rightarrow\text{4)}$ linkages.

Oxonium ion intermediate

A planar, resonance-stabilized carbocation intermediate formed during the glycogen synthase reaction following the departure of UDP prior to nucleophilic attack by the glycogen chain's C-4 hydroxyl group.

GS-I (Glycogen synthase I)

The active, dephosphorylated form of glycogen synthase whose enzymatic activity is independent of glucose-6-phosphate.

GS-D (Glycogen synthase D)

The less active, phosphorylated form of glycogen synthase that is dependent upon allosteric activation by glucose-6-phosphate for activity.

Glucagon

A 29-residue peptide hormone secreted by the pancreas that acts selectively on the liver and adipose tissue to stimulate glycogen breakdown and gluconeogenesis during fasting.

Epinephrine

A catecholamine 'fight or flight' hormone secreted by the adrenal glands that acts on liver and muscle tissues to rapidly trigger glycogen breakdown for acute energy release.

Adenylyl cyclase

A membrane-bound enzyme stimulated by $G_\alpha\text{(GTP)}$ that catalyzes the conversion of ATP into the second messenger cyclic AMP ($cAMP$) and pyrophosphate.

Cyclic AMP (cAMP)

An intracellular second messenger produced from ATP by adenylyl cyclase that binds to and activates Protein Kinase A (PKA), triggering a phosphorylation cascade.

Portal vein

A unique blood vessel that feeds an organ directly, transporting pancreatic endocrine secretions (such as insulin and glucagon) directly to the liver.