GLIKOLISISGLIKOLISIS

Major Pathways of Glucose Utilization

These three pathways are the most significant in terms of the amount of glucose that flows through them in most cells.

The Two Phases of Glycolysis

What is the net yield (in energy equivalents) per molecule glucose?

Glucose + 2NAD+ + 2ADP + 2Pi →2 pyruvate + 2NADH + 2H+ + 2ATP + 2H2O

Formation of 2 Pyruvates:

Glucose + 2NAD+ → 2 pyruvate + 2NADH + 2H+ ΔG’1O= -146 kJ/mol

Formation of 2 ATP:

2ADP + 2Pi → 2ATP + 2H2O ΔG’2O= 61.0 kJ/mol

Hexokinase: First ATP Utilization

Reaction 1 : Transfer of a phosphoryl group from ATP to glucose

to form glucose 6-phosphate (G6P)

ΔG’° = -16.7 kJ/mol

Phosphohexose Isomerase

Recation 2: Phosphohexose isomerase catalyzes the conversion of G6P to F6P, essentially the isomerization of an aldose to a ketose.

ΔG’° = 1.7 kJ/mol

PFK-1: Second ATP Utilization

Reaction 3: Phosophofructokinase-1 (PFK-1) phosphorulates fructose-6-phosphate (F6P)

PFK-1 plays a central role in control of glycolysisbecause it catalyzes on of the pathway’s rate determening reactions.

ΔG’° = -14.2 kJ/mol

Aldolase

Reaction 4: Aldolase catalyzes cleavage of fructose-1,6-bisphosphate (FBP)

ΔG’° = 23.8 kJ/mol

Triose Phosphate Isomerase

Reaction 5: Interconversion of the triose phosphates Only GAP continues along the glycolytic pathway Dihydroxyacetonphosphate is rapidly and reversible

ΔG’° = 7.5 kJ/mol

Glyceraldehyde-3-Phosphate Dehydrogenase

Reaction 6: Glyceraldehyde-3-phosphate dehydrogenase forms the first “high-energy” intermediate.

ΔG’° = 6.3 kJ/mol

Phosphoglycerat Kinase: First ATP Generation

ΔG’° = -18.5 kJ/mol

Phosphoglycerate Mutase

Reaction 8: Catalyzes of a reversible shift of the phosphoryl group between C-2 and C-3 of glycerate; Mg2+ is essential.

ΔG’° = 4.4 kJ/mol

Pyruvate Kinase : Second ATP Generation

ΔG’° = -31.4 kJ/mol

Lactate Fermentation

Enzyme = Lactate Dehydrogenase

Pyruvate + NADH + H+ L-Lactate + NAD+

Regenerates NAD+ from NADH (reducing equivalents) produced in glycolysis

Lactate fermentation is important in red blood cells, parts of the retina and in skeletal muscle cells during extreme high activity.Also important in plants and microbes growing in absence of O2.

ΔG’° = -25.1 kJ/mol

Alcoholic Fermentation

Two enzymes involved: Pyruvate decarboxylase irreversibleAlcohol dehydrogenase reversible

Pathway is active in yeast

Regenerates NAD+ from NADH (reducing equivalents) produced in glycolysis.

Second step is reversible → ethanol oxidation eventiually yields acetate

→ enters fat synthesis

The Pentose-Phosphate Pathway (PPP)

orThe Hexose-monophosphate Shunt

The Pentose Phosphate Pathway: Functions

1. Production of NADPH

2. Biosynthesis/degradation of other sugars(C3 ,C4, C5, C6, C7)

3. Biosynthesis and degradation of ribose

Determined by cell-specific needs for NADPH, ATP, sugars

Roles for NADPH

1. Reductant in biosynthetic reactions(e.g., fatty acid synthesis, steroid synthesis)

2. Production of reactive oxygen species (ROS)(e.g., innate immune response)

3. Regulation of redox homeostasis(e.g., erythrocytes, detoxification reactions)

4. Separation of catabolic and anabolic steps(e.g., in cytosol: low NADH, but high NADPH)

The Pentose Phosphate Pathway: Reactions

(Cytosol)

1. Oxidation Phase (C6 C5 + CO2)

2. Isomerization Phase (C5 C5)

3. Rearrangement Phase (xC5 yC6)

Phase 1: Oxidative Reactions