BIOCHEMISTRY

(Nurs MC 2)

METABOLISM OF CARBOHYDRATES
1. General Principles of Metabolism
2. Concentration of Sugar in the Blood
3. Source of Energy
4. Glycogenesis (report)
5. Glycogenolysis
6. Glycogen Storage Diseases
7. Glycolysis
8. Cori Cycle and Lactic Acid Pathway
9. Citric Acid Cycle
10. The Role of B-Vitamins in Citric Acid Cycle
11. Electron Transport Chain and Oxidative Phosphorylation
12. Gluconeogenesis
13. Hormones Involved in Regulating Blood Sugar

Objectives: Differentiate glycogenesis and glycogenolysis in terms of:

 Utilization of glucose
 Its role in biological systems
 Energy involved – Anabolic process (Anabolism), a biochemical process in metabolism where the
simple molecules combine to generate complex molecules.
 Steps/reactions involved including the enzymes required for each step

GLYCOGENESIS
GLYCOGEN METABOLISM: Glycogen, Glycogen Synthesis, and Glycogen Breakdown
A constant source of blood glucose is an absolute requirement for human life.
Glucose is the greatly preferred energy source for the brain and the required energy
source for cells with few or no mitochondria such as mature red blood cells.

Glycogenesis is the metabolic pathway by which glycogen is synthesized from glucose 6-

phosphate. Glycogenesis involves three reactions (steps).
Step 1: Isomerization: Formation of Glucose 1-phosphate.
The starting material for this step is not glucose itself but, rather, glucose 6-phosphate
(available from the first step of glycolysis). The enzyme phosphoglucomutase effects the change
from a 6-phosphate to a 1-phosphate.
Step 2: Activation: Formation of UDP-glucose. Glucose 1-phosphate from Step 1 must be
activated before it can be added to a growing glycogen chain. The activator is the high-energy
compound UTP (uridine triphosphate). A UMP is transferred to glucose 1-phosphate, and the
resulting PPi is hydrolyzed to 2Pi
Step 3: Linkage to Chain: Glucose Transfer to a Glycogen Chain. The glucose unit of
UDP-glucose is then attached to the end of a glycogen chain.
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In a subsequent reaction, the UDP produced in Step 3 is converted back to UTP, which
can then react with another glucose 1-phosphate (Step 2). The conversion reaction requires ATP.
Adding a single glucose unit to a growing glycogen chain requires the investment of two
ATP molecules: one in the formation of glucose 6-phosphate and one in the regeneration of UTP.

Location of Glycogenesis
Glycogenesis takes place in the cytoplasm of cells in the muscle, liver, and
adipose tissue.

Steps of Glycogenesis
Glycogenesis is a multistep process that takes place primarily in the liver and
muscle cells, although other tissues also contribute to glycogen synthesis. The
following steps outline the process of glycogenesis:

1. Glucose Uptake
 In this step, glucose molecules from the bloodstream are transported into
the liver or muscle cells through glucose transporters, such as GLUT2 in the
liver and GLUT4 in muscle cells.
 This facilitated diffusion process ensures an adequate supply of glucose for
glycogen synthesis within the cells.
 Reaction: Glucose + ATP → Glucose-6-Phosphate + ADP (Catalyzed by
hexokinase)
2. Conversion to Glucose-6-Phosphate (G6P)
 Once inside the cell, glucose is converted to glucose-6-phosphate (G6P)
through a phosphorylation reaction.
 The enzyme hexokinase or glucokinase catalyzes this reaction, using ATP as a
phosphate donor.
 The conversion of glucose to G6P traps glucose within the cell and makes it
more reactive for further metabolic processes.
 Reactions: Glucose + ATP → Glucose-6-Phosphate + ADP (Hexokinase
or Glucokinase)
3. Isomerization to Glucose-1-Phosphate (G1P)
 In this step, the G6P isomerizes to glucose-1-phosphate (G1P).
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 The enzyme phosphoglucomutase catalyzes this reaction by transferring the

phosphate group from the sixth carbon to the first carbon of the glucose
molecule.
 This isomerization is an essential step for the subsequent incorporation of
glucose into the growing glycogen chain.
 Reactions: Glucose-6-Phosphate ⇌ Glucose-1-Phosphate (Catalyzed by
phosphoglucomutase)
4. Activation of Glucose for Glycogen Synthesis
 To activate glucose for glycogen synthesis, G1P undergoes activation by the
enzyme UDP-glucose pyrophosphorylase.
 The reaction involves the transfer of UTP (uridine triphosphate) to G1P,
resulting in the formation of UDP-glucose and inorganic pyrophosphate
(PPi).
 This step ensures that glucose is energetically favorable for incorporation
into glycogen.
 Reactions: Glucose-1-Phosphate + UTP ⇌ UDP-Glucose + PPi (Catalyzed
by UDP-glucose pyrophosphorylase)
5. Glycogen Elongation
 Glycogen synthase, the key regulatory enzyme of glycogenesis, catalyzes the
elongation of the glycogen chain.
 It adds glucose units to the growing glycogen molecule by utilizing UDP-
glucose as the substrate.
 The enzyme forms an α-1,4-glycosidic bond between the glucose molecules,
extending the glycogen chain.
 Reactions: UDP-Glucose + Glycogen (n residues) → Glycogen (n+1
residues) + UDP (Catalyzed by glycogen synthase)
6. Branching of Glycogen:
 When the glycogen chain reaches a certain length, branching occurs to
ensure efficient synthesis and degradation of glycogen.
 The branching enzyme, α-1,6-glucosyltransferase, catalyzes the transfer of a
segment of the glycogen chain and attaches it via an α-1,6-glycosidic bond.
 This branching creates branches within the glycogen structure, allowing for
easier access by enzymes involved in glycogen synthesis and breakdown.
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 Reaction: Glycogen (n residues) → Glycogen (n-1 residues) + Glycogen

(m residues) (Catalyzed by branching enzyme, α-1,6-
glucosyltransferase)

Control and Regulation of Glycogenesis

The process of glycogenesis is strictly regulated and controlled by various
important elements in order to maintain glucose homeostasis. These systems
make sure that glycogen synthesis happens when the body needs energy
storage and glucose levels are high.
 Insulin and glucagon are the two main hormones that regulate
glycogenesis.
 The hormone insulin, which is secreted by the pancreas, is crucial in fostering
glycogenesis.
 When blood glucose levels rise, insulin is produced to aid in glucose
absorption by cells and promote the creation of glycogen.
 Glycogen synthase is made more active by insulin, which also encourages
the conversion of G1P to glycogen.
 Contrarily, when fasting or low blood sugar, glucagon counteracts the
actions of insulin and controls the metabolism of glycogen.
 Although the pancreas also secretes it, it works against insulin.
 Glucagon suppresses gluconeogenesis while stimulating glycogenolysis, the
process by which glycogen is broken down.
 This is accomplished by blocking glycogen synthase and turning on
glycogen phosphorylase, the enzyme that breaks down glycogen.

Toggle Control and Regulation Subsection

An extra degree of regulation exists in addition to the hormonal control
provided by glucagon and insulin in the form of covalent alteration of
glycogen synthase and glycogen phosphorylase.
 Toggle control is the technique of reversibly phosphorylating certain
enzymes to either activate or deactivate them. Protein kinase A (PKA)
phosphorylates glycogen synthase to decrease its activity and stop
glycogen production.
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 Glycogen synthase is dephosphorylated by protein phosphatase 1 (PP1) to

become active and encourage glycogen synthesis while PKA is inactive.
 Phosphorylation controls the activity of glycogen phosphorylase as well.
 Dephosphorylated glycogen phosphorylase is inert, whereas phosphorylated
glycogen phosphorylase catalyzes the breakdown of glycogen.
Epinephrine (Adrenaline)
The adrenal glands release the hormone epinephrine, sometimes known as
adrenaline, during times of stress or physical activity. To provide a quick
supply of glucose for energy, epinephrine triggers the breakdown of glycogen.
Glycogen phosphorylase is phosphorylated and activated by PKA, which also
inhibits glycogen synthase. This is accomplished through a signaling
mechanism.

Calcium Ions
 Additionally, calcium ions are crucial for controlling glycogen metabolism.
 Glycogen phosphorylase is activated and glycogen breakdown is promoted
by elevated intracellular calcium concentrations, which are frequently
brought on by muscular tension.
 This is accomplished by calcium ions binding to calmodulin, which activates
the CaMK protein kinase.
 Phosphorylase kinase is then phosphorylated and activated by CaMK, which
in turn phosphorylates and activates glycogen phosphorylase.