1) Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that protects red blood cells from oxidative stress by producing the antioxidant reduced glutathione. 2) Mutations in the G6PD gene can cause G6PD deficiency, leaving red blood cells vulnerable to oxidative stress triggered by foods like fava beans. 3) Favism is a result of G6PD deficiency where eating fava beans causes hemolysis and jaundice due to oxidative damage to red blood cells from lack of reduced glutathione.

1. Normal Function
•Carbohydrates breakdown
•Produce NADPH
•Protects RBCs from oxidative
stress
•Reduces Glutathione
•Reduced glutathione
important for proper RBC
structure and to keep
hemoglobin in ferrous state.
The Role of Glucose-6 Dehydrogenase in Favism
Fatima Abdularahman, Nanaama O’Hene, Kene Ezeigwe, Flor Lema
Introduction
Glucose-6 Dehydrogenase (G6PD) is a cytosolic, regulatory
enzyme. Its main role is the catalysis of the first step of the
Pentose Phosphate Pathway of glucose metabolism which is the
oxidation of glucose-6-phosphate. In oxidizing
glucose-6-phosphate, G6PD reduces NADP to produce NADPH.
The production of NADPH is the most important function of
G6PD as NADPH is required for a variety of detoxification
reactions. More specifically, NADPH is responsible for the
reduction of glutathione. This reduced form of glutathione in
turn neutralizes free radicals to protect cells from oxidative
stress.
The clinical significance of G6PD lies in the variety of
enzymatic activity associated with the genetic diversity of G6PD
caused by various mutations. Many of these mutations lead to a
G6PD deficiency in the body which eventually leaves red blood
cells vulnerable to oxidative stress. Favism is one result of G6PD
deficiency as the consumption of fava beans causes oxidative
stress.
G6PD Gene
Glucose-6-phosphate dehydrogenase deficiency is a genetic
disorder. It is an X-linked recessive disorder that occurs most often
in males.
A mutation in the gene can change the amino acid
sequence in the protein that codes for the gene. Thereby,
disrupting the structure and function of the enzyme.
mutations lead to changes in single building blocks (amino acids)
that make up the glucose-6-phosphate dehydrogenase enzyme.
These changes disrupt the normal structure and function of the
enzyme or reduce the amount of the enzyme in cells.
This condition mainly affects red blood cells, which carry
oxygen from the lungs to tissues throughout the body.
Structure
G6PD exists as either a
dimer or a tetramer which
exists as a dimer of dimers.
Each subunit of the dimer
consists of two domains. The
smaller domain contains the coenzyme binding site
and is a dinucleotide-binding fold. The larger domain
is a beta + fold consisting of a nine-stranded beta
sheet. In humans, G6PD is normally in a rapid
dimer-tetramer equilibrium although high pH often
causes tetramers to dissociate into dimers. At low
pH, the equilibrium is shifted towards tetramers.
Mutations have been found to cause structural
deformities and deficiencies predominantly close to
the structural NAD+ interface.
Acknowledgements
First and foremost, we would like to thank Rutgers Robert Wood
Johnson Medical School and the Biomedical Careers Program for
hosting such a wonderfully engaging and educational summer
enrichment program. We would also like to thank our instructor
and T.A, Dr. Mohammad and Brian DePalma for their commitment
to teaching and guiding us throughout the length of the program.
Favism
Pathology: Mutation in G6PD gene → G6PD Deficiency → No NADPH → No reduced
glutathione (antioxidant) → free radicals not neutralized → oxidative stress → RBCs
damage
Cause: G6PD Deficiency
Main Symptoms:
- Jaundice- → Abundant hemoglobin breaks down into bilirubin (pigment) → liver overload
→ jaundice
→ hemolytic anemia (RBCS break down prematurely)
Triggered by: fava beans, legumes, antimalarial drugs, moth balls
Diagnosis: Umbilical cord blood, CBC, blood test, check bilirubin levels, reticulocyte count
First Line of Treatment: Phototherapy (for Neonatal Hyperbilirubinemia) and Dietary
restrictions
Other Treatment: Blood Transfusions
Carriers are partially protected against malaria because with less functional G6PD it is
difficult for the parasite to invade red blood cells. Parasites need the reduced glutathione
to grow.
Why Fava Beans?
Pamaquine (a purine glycoside) generates peroxides, which results in oxidative stress.
References
Au, Shannon Wn, Sheila Gover, Veronica Ms Lam, and Margaret J Adams. "Human Glucose-6-phosphate Dehydrogenase: The Crystal Structure
Reveals a Structural NADP Molecule and Provides Insights into Enzyme Deficiency." Structure 8.3: 293-303. Print.
Scopes, Deborah A., Jose M. Bautista, Claire E. Naylor, Margaret J. Adams, and Philip J. Mason. "Amino Acid
Substitutions at the Dimer Interface of Human Glucose-6-phosphate Dehydrogenase That Increase Thermostability
and Reduce the Stabilising Effect of NADP." Eur J Biochem European Journal of Biochemistry 251.1-2: 382-88. Print
www.ncbi.nlm.nih.gov/books/NBK22389/
http://g6pddeficiency.org/wp/#.VZb4F_lVikp