PENTOSE

PHOSPHATE
PATHWAY
 Pentose Phosphate Pathway
• Otto Warburg
• Frank Dickens
Dr. Bernard L. Horecker
OVERVIEW
Functions
1. To generate reducing equivalents,
in the form of NADPH, for reductive
biosynthesis reactions within cells.
2. To provide the cell with ribose-5-
phosphate (R5P) for the synthesis of
the nucleotides and nucleic acids.
3. Although not a significant function
of the PPP, it can operate to
metabolize dietary pentose sugars
derived from the digestion of nucleic
acids as well as to rearrange the
carbon skeletons of dietary
carbohydrates into
glycolytic/gluconeogenic
intermediates.
 Overall Reaction for Stage 1

• 3G6P + 6NADP+ 3H2O ->

6NADPH + 6H+ 3CO2 +3Ru5P
 •The reactions of the PPP operate in the cytoplasm.
•The pentose phosphate pathway has both an oxidative
and a non-oxidative arm.
•The reactions catalyzed by glucose-6-phosphate
dehydrogenase and 6-phosphogluconate dehydrogenase
each generate one mole of NADPH each for every mole of
glucose-6-phosphate (G6P) that enters the PPP.
•The non-oxidative reactions of the PPP are primarily
designed to generate R5P.
•The primary enzymes involved in the non-oxidative steps
of the PPP are transaldolase and transketolase
•The net result of the PPP, if not used solely for R5P
production, is the oxidation of G6P, a 6 carbon sugar, into a 5
carbon sugar.
 Products

NADPH
R5P
Intermediates for Glycolysis
 Metabolic Disorders
Ribose-5-phosphate isomerase Deficiency-
results to New Inborn Error in the Pentose
Phosphate Pathway Associated with a Slowly
Progressive Leukoencephalopathy
Transaldolase Deficiency- influences the
pentose phosphate pathway, mitochondrial
homeostasis, and apoptosis signal processing. 
Glucose-6-phosphate dehydrogenase
Deficiency- the MOST COMMON human
enzyme defect
Glucose-6-Phosphate Dehydrogenase Deficiency
•Characterized by abnormally low levels of G6PD levels
•More than 400 different variants of G6PD Deficiency
have been identified
•G6PD deficiency was discovered as an outgrowth of an
investigation of hemolytic anemia occurring in some
individuals treated for malaria .
•The modern understanding of the condition began with
the analysis of patients who exhibited sensitivity
to primaquine.
•600 million people are affected by this disease
•Occurs mainly in Africa, Asia and the Meditteranean
•Affects 1 out of 10 African-American males in the US
WORLDWIDE DISTRIBUTION OF G6PD DEFICIENCY
What are the causes of G6PD
Deficiency?
•G6PD Deficiency is inherited from one or both of
your parents. It cannot be passed from one person
to another in any other way.

•Males can either be G6PD Deficient or unaffected.

Females can be G6PD Deficient, partially deficient
(sometimes known as carriers) or unaffected.
Inheritance of G6PD Deficiency
 Favism
G6PD Deficiency Disorders
HEMOLYTIC ANEMIA- abnormal
breakdown of red blood cells (RBCs) either
in the blood vessels (intravascular
hemolysis) or elsewhere in the body
(extravascular).
FAVISM- a disorder characterized by
hemolytic anemia in response to ingestion
of fava beans.
CATARACT- a clouding that develops in
the crystalline lens of the eye or in its
envelope, varying in degree from slight to
complete opacity and obstructing the
passage of light.
Anemia
In the hexose monophosphate pathway, glucose-6-phosphate
dehydrogenase forms most of the reduced nicotinamide adenine
dinucleotide phosphate (NADPH) in cells which is necessary for the
reactions of various biosynthetic pathways, the stability of catalase and the
regeneration of reduced glutathione (GSH) from the oxidised glutathione
(GSSG).

The reduced form of NADPH, catalase and GSH are the main antioxidants
of cells. In this way glucose-6-phosphate dehydrogenase provides a source
of reducing power in the form of sulfhydryl buffers that maintains the
integrity of protein and lipid sulfhydryl groups and aids in the
detoxification of free radicals and peroxides

In the red blood cells of glucose-6-phosphate dehydrogenase deficient

subjects, structural changes will occur during oxidative stress owing to
disulphides build up. In turn this causes haemoglobins to denature and
precipitate as lumpy particles known as Heinz bodies which attach to the
cell membrane and alter its charge, elasticity and permeability.
SYMPTOMS OF ANEMIA
 
•paleness (in darker-skinned
children paleness is sometimes
best seen in the mouth, especially
on the lips or tongue)
•extreme tiredness
•rapid heartbeat
•rapid breathing or shortness of
breath
•jaundice, or yellowing of the skin
and eyes, particularly in newborns
an enlarged spleen
•dark, tea-colored urine
FAVISM

• Fava beans are rich in two glycosidic compounds, vicine and

convicine

•Upon ingestion, the glycosides are hydrolysed enzymatically

to form pyrimidine aglycones, divicine and isouramil
respectively.

•The proposed mechanism for the cause of favism is that these

new compounds then undergo redox cycling and in the process
depleting reduced glutathione (GSH), leading to the formation
of free radicals and hydrogen peroxide.
CATARACTOGENESIS

•The idea that cataractogenesis and glucose-6-phosphate

dehydrogenase deficiency are linked was first proposed by Zinkham in
1961.

•The cells of the mammalian lens have many properties in common with
the red blood cell. This underlines the argument of the importance of
glucose-6-phosphate dehydrogenase in maintaining the levels of
reduced NADPH available for preventing the oxidation of sulfhydryl (-SH)
groups in lenticular cells. In glucose-6-phosphate dehydrogenase
deficiency there is a decreased synthesis of ribose and a lower turnover
of proteins. Coupled with the low levels of reduced glutathione, this
might reduce the solubility of membrane proteins exposed to oxidative
stress. Following this, high molecular weight protein (S-S) aggregates are
believed to form in the lens and cause cataract development
TREATMENT
•There is no known cure for G6PD Deficiency.
It is a lifelong condition
• People with G6PD Deficiency may use a list
of prohibited food and chemicals to help
them prevent severe reactions
•Common theme among these food and drug
is that all of them are oxidizing agents
 Some Prohibited Food and Chemicals
for G6PD Deficiency Patients
Foods to be avoided:
Fava Beans - Dingdong nuts, Mr. Bean
Redwine
Legumes - Habitswelas, Garbanzos, Kadyos or Black Beans, Monggo
Blueberry
Soya Food - Taho, Tofu or Tokwa, Soy Sauce Chemicals to be avoided:
Tonic Water Methylene Blue
Bitter Melon or Ampalaya Arsine
Herbs to be avoided: Phenylhydrazine
Cattle gallstone bezoar Toluidine Blue
Honeysuckle flower Trinitrotoluene
Chimonanathus flower Aniline Eyes
100% Pearl powder Camphor
Figwortflower Napthalene
Acalypha indica Henna
Menthol
Alaxan Gel
Begesic
G6PD Deficiency Advantage
•Both the hemizygous G6PD deficient male and
homozygous G6PD deficient female are protected against
falciparum parasitization.

• Erythrocytes from all G6PD deficient genotypes are relatively

protected against falciparum infestation, and that this protection
is enhanced by oxidant substances derived from a number of food
crops such as fava beans.
WORLDWIDE DISTRIBUTION OF MALARIA
REFERENCES
•http://G6pddeficiency.org
•http://bloodjournal.hematologylibrary.org/cgi/content/full/111/1/16
•http://rialto.com/g6pd/
•http://kidshealth.org/parent/general/aches/g6pd.html#
•http://teekoonhien.fortunecity.com/g6pdbiochemistry.html
•Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial
homeostasis, and apoptosis signal processing. 
Y Qian, S Banerjee, CE Grossman, et. Al
•Ribose-5-Phosphate Isomerase Deficiency: New Inborn Error in the Pentose Phosphate
Pathway Associated with a Slowly Progressive Leukoencephalopathy
Jojanneke H.J. Huck1, 2, Nanda M. Verhoeven2, et al
•G6PD Deficiency as Protection Against falciparum Malaria: An Epidemiologic Critique of
Population and xperimental Studies by LAWRENCE S. GREENE
A SWEET QUESTION FROM GROUP 2

HOW MANY SWEETS WERE USED AS THE

BACKGROUND PICTURE IN THIS
POWERPOINT PRESENTATION? :D