Minor carbohydrate pathways

(Ribose/Pentose, Fructose & Galactose)

Biomedical Sciences for Optometry I

(OPT 2034)

Dr. Christinal Teh

christinaltehpw@segi.edu.my
 Learning Objectives & Outcomes

• At the end of this lecture, students should be able to

discuss the
1. Pentose phosphate pathway
2. Galactose metabolism
3. Fructose metabolism
Fructose Galactosemia
Intolerance
 Ribose/Pentose metabolism

• Hexose monophosphate shunt

• Pentose phosphate shunt/pathway
Just to confuse you
• 6-phosphogluconate pathway
• Dickens-Horecker pathway
• Main fn. to syn. (1) NADPH (2) ribose-5 phosphate for DNA/RNA
(the significance of these two compounds)
• The pathway has traffic:-
• Irreversible oxidative (cannot U-turn)  generate NADPH
• Reversible non-oxidative (U-turn allowed)  generate ribose
• The rate and direction of the reversible reaction is important and
is determined by the demand and supply of the cycle
 Non-oxidative phase
Reversible
Non-reversible

Reversible
Oxidative phase
FA biosynthesis; prevent oxidative
damage by reducing glutathion

DNA and RNA

synthesis

Overall Equation:
Glucose-6-P  2 NADPH + Ribose-5-P

Thiamine-PyroPhospate (Co-factor for transketolase, pyruvate

DH and α-ketoglutrate DH)
Irreversible oxidative reaction: No return

• Two portions; both which are oxidative

(remove H; and produces a molecule of NADPH):-
1. The dehydrogenation of glucose-6-phosphate
2. Formation of ribulose-5-phosphate
 Oxidative Phase
1. Dehydrogenation of Glucose-6-Phosphate
• Glucose-6-phosphate → 6-phosphogluconolactone
• One molecule of NADPH is formed
• E: Glucose-6-phosphate dehydrogenase (DH)
- rate limiting enzyme
• NADP+ as co-enzyme
• NADPH/NADP+ ratio is important
High  inhibits the enzyme activity
Low  Promotes the enzyme activity
2. 6-phosphogluconolactone → 6-phosphogluconate
E: 6-phosphogluconolactone hydrolase

3. Formation of Ribulose-5-Phosphate

• 6-phosphogluconate  Ribose-5-phosphate
• E: 6-phosphogluconate dehydrogenase
• Intermediate compound: 3-keto-6-phosphate gluconate
• 6-phospogluconate is reduced then decarboxylised
(remove C)  5 C
Combined: Oxidative decarboxylation
• 1 NADPH and 1 CO2 is formed
• Product: Ribulose-5-phosphate
(1) glucose-6-phosphate DH; (2) 6-phosphogluconate DH;
(3) ribose phosphate isomerase
 Non-oxidative Phase

4. Formation of the ribose-5-phosphate

• Ribulose-5-P  Ribose-5-P (E: isomerase) “rearranged”
 Xylulose-5-phosphate (E: epimerase)
• Ribose-5-P is the pre-cursor for DNA/RNA synthesis
• This is a reversible reaction
(4) ribose 5-phosphate isomerase;
(5) phosphopentose epimerase
Reversible non-oxidative reaction: U-turn

• Occur in all type of cells that synthesize nucleic acids

• Involves : inter-conversion of sugars
• 3 Transfers
• Transfers of carbons:-
1. Trans-ketolase (transfer 2C) – step 6
2. Trans-aldolase (transfer 3C) – step 7
3. Second transketolase reaction (transfer 2C) – step 8
 1

1: 5C + 5C  7C + 3C (2C is moved to 5C molecule by transketolase)

STEP 1
 2

2: 7C + 3C  4C + 6C (3C is moved to 3C molecule by transaldolase)

STEP 2
 3

3: 4C + 5C  6C + 3C (move 2C to 4C molecule by transketolase)

STEP 3
Ribose/Pentose metabolism
 The angelic NADPH
Phagosome digestion
NADPH oxidase  Fatty acid
superoxide free radical; Reduces
synthesis oxidants
myeloperoxidase 
H2O2 such as
hydrogen
peroxide

NADPH
Synthesis of Nitric Reducing agents for
oxide (NO) for Cytochrome P450
vasodilation, (mono-oxygenase) 
neurotransmitter, synthesis cholesterol,
prevent platelet steroid hormones;
aggregation detoxification of drugs
NADPH in maintaining Glutathione levels
• Glutathione is the natural antioxidant  H2O2
• NADPH sacrifices itself to maintain the levels of
reduced glutathione
Sulfhydryl link

1 2
 Full circle: G6PD

• Erythrocytes fully dependant on the G6PD to syn. NADPH as

a source of antioxidant (other mech. for diff cells)
• Deficiency of glucose-6-phosphate DH
• NADPH not produced sufficiently
• Leads to:-
1. Less reduced glutathione
2. Increased oxidative stress (ROS)
3. Damaged cell wall
4. Hemolysis

X-linked mutations tend to be rare in women

NADPH in the RED BLOOD CELL
Sulfhydryl link
 Heinz
• Not the ketchup

• Aggregates of cross-linked Hb

• These insoluble masses on the cell membrane

= heinz bodies

• Membrane proteins become more

rigid + ROS attack cell membrane
= hemolysis

• Removed by macrophages
 Fructose metabolism

• Fructose is metabolized to products that enter the

glycolytic pathway
• Location: Liver
• E1: Fructokinase (Fructose  Fructose-1-phosphate)
(Deficiency: Fructosuria)
• E2: Aldolase B (F-1-P  Dihydroxy-acetone-phosphate
+ Glyceraldehyde) (Deficiency: Fructose intolerance)
• E3: Triose kinase (Glyceraldehyde  Glyceraldehyde-3
phosphate)
 Galactose metabolism

• Galactose is metabolized to products that enter the

glycolytic pathway

• Location: Liver

• E1: Galacto kinase (Deficiency: Cataracts)

Galactose  Galactose-1-P

• E2: Galactose-1-Phosphate Uridy-lyl-transferase (the

switch) (Deficiency: Galactosemia)
UDP(uridine diphosphate)-Glucose + Galactose-1-P
 UDP- Galactose + Glucose-1-Phosphate

• E3: UDP-Glucose Isomerase

(UDP-Galactose  UDP-Glucose)