Mulungushi University

School of Medicine and Health Sciences

Pharmacy program

Ms. Ngosa M

Prepared by: Dr. Masenga SK, PhD

Carbs_ Pentose Phosphate and Uronic
acid Pathway

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 NOTE
•These notes are complemented by the
accompanying Oral didactic lecture, to
enhance student participation,
involvement and engagement. Please
attend the Oral presentation to complete
your notes!!

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 OBJECTIVES
• Overview of the pentose phosphate pathway and its
roles
• Overview of the Uronic acid pathway and its
importance
• Understand the consequences of large intakes of
fructose.
• Synthesis and importance of galactose.
• Clinical aspects

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Terminologies:
• Pentose phosphate pathway (PPP) AKA hexose
monophosphate shunt AKA Phospogluconate
pathway
• metabolic pathway parallel to glycolysis that generates
NADPH and pentoses (5-carbon sugars) as well as ribose 5-
phosphate.

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Principles
• Occurrence – all cells cytoplasm ( most active : liver,
mammary gland, thyroid, testes, erythrocytes, adrenal
cortex; low activity skeletal muscle & non lactating
mammary gland)

• Primary role – anabolic rather than catabolic (glucose)

• Products
• NADPH and pentoses

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Principles
• Phases and products
• NADPH – oxidative phase -Fatty acid synthesis (50%),
Oxidative stress homeostasis (free radical reactions),
Cytochrome p450 enzymes, Cholesterol metabolism,
Neurotransmitter synthesis
• Pentoses – non oxidative phase - nucleotide and nucleic
acid synthesis

• Runs parallel to glycolysis – more complex

• Unlike glycolysis, oxidation is achieved by dehydrogenation
using NADP+, not NAD+, as the hydrogen acceptor.
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 The pentose phosphate pathway.
(P, —PO32–; PRPP, 5-phosphoribosyl
1-pyrophosphate.)

Irreversible AKA 6-phosphogluconolactone

oxidative phase Gluconolactone hydrolase

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Differences between glycolysis and pentose
phosphate pathway
Glycolysis PPP
Oxidation occurs utilizing NAD+ as an Oxidation occurs utilizing NADP as an
H-acceptor H-acceptor
Aerobic as well as anerobic process Anaerobic process
CO2 is not produced at all CO2 is a characteristic product
2 ATP is generated ATP is not generated
Ribose phosphates are not generated Ribose phosphates are generated
Occurs in all cells Occurs in certain cells
80-90% of glucose oxidized by 10-20% of glucose oxidized by PPP
glycolysis
Oxidation step is late (GAPDH) Oxidation is first step (direct pathway)
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
PPP reduces oxidant stress Via glutathione
peroxidase

The PPP & glutathione peroxidase protect

erythrocytes against hemolysis

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Uronic acid pathway
• Is an alternative pathway for the oxidation of Glucose
• Occurs in the cytoplasm
• Major function is Production of UDP-glucoronic acid
(active form of glucuronic acid) Important for:
• Conjugation of bilirubin, steroids, various drugs and synthesis of
glycosamino glycans (GAG)
• Synthesis of mucopolysaccharides (mps) (D-Glucoronic acid)
• Detoxification of foreign chemicals (D-Glucoronic acid)
• Does not produce ATP but utilizes it for generation of
UDP-glucoronic acid
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Fructose metabolism

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Fructolysis
• Fructose is metabolized almost completely in the liver
→ liver glycogen and triglyceride synthesis
• also metabolized in intestine, testis, kidney, skeletal
muscle, fat tissue and brain
• not transported into cells via insulin-sensitive
pathways but GLUT5 because fructose is not an
insulin secretagogue
• Fructose bypasses the 2 regulatory steps hence
produces more ATP-→ Increased fat accumulation
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Differences between Fructolysis and glycolysis.
Fructose:
• Insulin dependence: No
• Transporters: GLUT 5
• Rate of metabolism: Rapid, bypass rate limiting step
PFK-1
• Sites: Liver , kidney, intestines, brain
• Purpose: Replenish Liver glycogen & TAG synthesis
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
 Metabolic consequences of large fructose
quantity Ingestion
• Floods glycolysis flux hence ↑fatty acid synthesis, and secretion
VLDL, →↑ serum triacylglycerols → LDL cholesterol
concentrations.
• the fate of much of the fructose metabolized in the liver is
Gluconeogenesis
• A positive relationship has been demonstrated between
fructose intake and uric acid levels
• predicts LDL particle size in overweight school children
• Acutely elevates blood pressure
• Fructose consumption increases the risk of gout in humans
Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm
• Loading of the Liver With Fructose May Potentiate
Hypertriacylglycerolemia, Hypercholesterolemia, &
Hyperuricemia

• Fructose & Sorbitol in the Lens Are Associated With

Diabetic Cataract

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm

 Tip to understanding and learning how to learn
• Metaphor: As a farmer, you wet the ground and check that
all surfaces are wet and ready for digging (snapshot), then
start digging, turning over all the sand that stands in the way
• APPLICATION:
• Have a snapshot of the pathways/information
• To understand the big picture and recall the pillars (essential parts)
• Then read through the detail again to familiarize
• Look out for intermediates
• Read the enzymes
• Important metabolites & their usage

Dr. Sepiso Masenga ~ Lectures smasenga@mu.ac.zm