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Glucose and Carbohydrate Metabolism

• Glycogen Overview
    - Glycogen is the readily metabolized storage form of glucose.
    - It is a branched homopolymer of glucose.
    - Linkages are _____________________.
    - Glucose can be added and removed from the _____________________ of glycogen = ____________
    - Thus, ________________ in glycogen create more ends to either add or remove glucose.

• Glycogen Function
    - In Liver
      - The synthesis and breakdown of glycogen is regulated to ____________________________.
    - In Muscle
      - The synthesis and breakdown of glycogen is regulated to _______________________________ of the muscle cell.
    - When blood glucose levels fall, glycogen will be broken down to release glucose units.
    - Glycogen breakdown = __________________
    - Glycogenolysis is a __________________ process.
    - Requires 3 enzymes:
      1. Glycogen phosphorylase
      2. Phosphoglucomutase
      3. Glycogen debranching enzyme
    - Glycogen has a branched structure with 14 linkages and 16 branches' non-reducing ends.
    - Free 40H branches maintain blood glucose levels to meet energy requirements.
    - Glycogenolysis is categorized as a catabolic process.

Glycogen Phosphorylase

• Functionality
    - Glycogen Phosphorylase can only cleave __________________.
    - It is important to note that Glycogen Phosphorylase is a Phosphorylase, NOT a Phosphatase.
    - A Phosphorylase enzyme: __________________
    - A Phosphatase enzyme: __________________.
  
  

• Importance of Enzyme Type
    - There are 2 key reasons why it matters which type of enzyme is used:
      - Reason A:
        - If attacked with H2O (phosphatase), it would result in __________________ (instead of G1P).
        - This would require the use of ATP to phosphorylate glucose to G6P in glycolysis = _______________.
        - In contrast, since phosphorylase uses Pi to attack, only a transfer of phosphate occurs from G1P to G6P = __________________.
      - Reason B:
        - Phosphorylase yields G1P, which is charged = __________________.

• Cofactor Requirement
    - Glycogen Phosphorylase requires a vitamin cofactor:
      - Pyridoxal Phosphate (PLP).
      - Derived from Pyridoxine
    - Function of PLP:
      - The phosphate of PLP participates in acid/base catabolism.
      - The hydrophobic ring of PLP helps ___________________________ (along with Pi).
    - NOTE: PLP is also a required cofactor for enzymes in amino acid metabolism.
    - Structure of PLP includes:
      - N-H-C=O-P=O−-O-OH-CH3-C-H-O− + H2
    - Acts as both a proton donor and proton acceptor in reactions.

Glycogen Phosphorylase Functionality

• Characteristics
    - Glycogen Phosphorylase is a __________________ enzyme.
    - It simply _______________________________ the glycogen polymer, cleaving off residues without having to dissociate and rebind after each reaction.
    - What other enzymes conduct similarly? (hint: think of last semester)

• Conversion Process
    - Glycogen phosphorylase releases ____________ which need __________________ to enter glycolysis.
    - NOTE: G6P (Glucose-6-Phosphate) can bypass the 1st reaction of glycolysis (hexokinase reaction) and directly go to the 2nd reaction.
    - Glycogen phosphorylase cleaves ONLY at _____________________ and NOT at ______________________.
    - In fact, it will stop 4 residues before reaching a branch point.

• Branch Removal
    - How are branches removed from glycogen?
      - Through a Glycogen Debranching Enzyme.
      - Glycogen phosphorylase stops 4 residues away from a branch point.
      - The debranching enzyme shifts 3 glycosyl units from one strand to another.
      - Then it hydrolyzes the remaining α(1-6) sugar using water to yield 1 free glucose.

Glycogen Breakdown in Muscle vs. Liver

• Functional Differences
    - In the Liver:
      - Releases free glucose into the blood.
    - In the Muscle:
      - Uses G6P for its own energy.
    - The liver can release free glucose to the blood for uptake by the brain and active muscle.
    - The liver regulates _______________________________ (blood glucose levels).

• Consequence in Muscle
    - Muscle does not have ______________________________.
    - As a consequence, the muscle retains G6P for its own energy.
    - Note: Phosphorylated glucose is trapped in the cell.
    - Without G6P Phosphatase, it cannot convert back to free glucose for release.