11/23/2013

1

GLYCOLYSIS

BIOCHEMISTRY Carbohydrate Catabolism

(Metabolism)

Carbohydrates are the primary source of

cellular energy for most organisms

Glucose is the most commonly used

carbohydrate and will always be used first

Generates ATP and other high-energy

compounds by breaking down carbohydrates:

glucose + oxygen carbon dioxide + water

Carbohydrate Catabolism (Metabolism)

Two methods for ATP productions via catabolism

of glucose

1. Cellular Respiration

- Requires oxygen to serve as the final electron acceptor in

a series of redox reactions

- Generate ATP by oxidative phosphorylation

- Most efficient method of ATP production

- 1 glucose generates 36 ATP

- Involves reaction performed inside the mitochondria

Carbohydrate Catabolism (Metabolism)

Two methods for ATP productions via catabolism

of glucose

2. Fermentation

- Requires an organic molecule to serve as the final electron

acceptor

- Can be done in the absence of oxygen

- ATP is synthesized using substrate level phosphorylation

- Less efficient, 1 glucose generates 2 ATP

- In humans, results in lactic acid

Anaerobic Vs. Aerobic Respiration

Glycolysis

Anaerobic reactions: Fermentation

Do not require oxygen

Example: Glycolysis

Breaks down glucose in cytosol:

into smaller molecules used by mitochondria

Aerobic reactions: Cellular Respiration

Occur in mitochondria:

consume oxygen

produce ATP

Aerobic Respiration of Glucose

C6H12O6 + 6O2 6 CO2 + 6H2O

Three Stages

1. Glycolysis

- Oxidation of glucose to pyruvic acid

- Some ATP and NADH produced

2. Citric Acid Cycle

- Oxidation of acetyl to carbon dioxide

- Some ATP, NADH and FADH produced

3. Electron Transport Chain

- NADH and FADH2 are oxidized providing electrons for redox reactions

- coenzymes that function to transport electrons in the form of hydrogen

- Reduce oxygen to generate ATP

- Majority of ATP is produced at this step

11/23/2013

2

Nutrient Use in

Cellular Metabolism

Figure 25–2 (Navigator)

Glycolysis (Anaerobic Process)

Does not require oxygen

Occurs in cytoplasm

10 step metabolic pathway:

Catabolizes and oxidizes one 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules

Generates 2 ATP by substrate level phosphorylation

Many cells can survive on glycolysis alone

Not very efficient

Generates lactic acid as a waste product

Needs to be removed and processed to prevent

Drastic alterations in pH

Loss of homeostasis

Glucose can also be available from food intake.

Glucose is also stored as glycogen (glycogenesis).

After gluconeogenesis, glucose is converted from glycogen in liver or muscle for glycolysis.

Glycolysis Factors

Glucose molecules

Cytoplasmic enzymes

ATP and ADP

Inorganic phosphates

NAD (coenzyme)

Glycolytic Pathway

Glycolysis glucose is converted via fructose-1,6-

bisphosphate to pyruvate with the generation of 2

mol of ATP/mol of glucose central to most

metabolism

Several other metabolic pathways feed into the

glycolytic pathway

Also known as Embden-Meyerhof-Parnas Pathway

6 carbon sugars (hexoses - glucose and fructose) are converted to 3 carbon sugars (trioses - dihydroxyacetone, glyceraldehyde, and pyruvate)

11/23/2013

3

Overall Reaction of Glycolysis

Glycolysis takes place within the cytosol of the cell

The products all have vital cellular uses:

• ATP energy source for many cellular functions

• NADH + H+ provides reducing power for other metabolic

pathways or further ATP synthesis.

• Pyruvate used in the citric acid cycle in aerobic respiration

to produce more ATP, or is converted to other small carbon

molecules in anaerobic respiration

Glycolysis

Glycolysis The sequence reactions that convert

glucose into pyruvate Reactions : 10 steps

Pi = orthophosphate (PO43-)

ADP = adenosine diphosphate

ATP = adenosine triphosphate

UDP = uridine diphosphate

NAD+ = nicotinamide adenine dinucleotide, oxidized form

NADH = nicotinamide adenine dinucleotide, reduced form

NADP+ = NAD phosphate, oxidized form

NADPH = NAD phosphate, reduced form

10 Steps of Glycolysis

Reaction 1 - 3 Reaction 4 - 6

11/23/2013

4

Reaction 7 - 10 The final product of glycolysis is pyruvate

Under anaerobic conditions in humans (as in muscle during a sprint) pyruvate is reduced to lactate via lactate dehydrogenase

Glucose + 2 ADP + 2 Pi 2 lactate + 2 ATP + 2 H+

Under aerobic conditions in humans, pyruvate is oxidized to CO2 via pyruvate dehydrogenase and the citric acid cycle in the mitochondrion

Oxidative Decarboxylation

Not technically a reaction of glycolysis, but is very

common in most organisms as a link to the citric

acid cycle

Carried out in the mitochondria, unlike the reactions

of glycolysis which are cytosolic

Two Stages in Glycolysis

1. Preparatory Stage:

- Enzyme phosphorylates last (sixth) carbon atom of glucose molecule:

1. Glucose-6-phosphate is formed using 1 ATP molecule

- traps glucose molecule within cell

2. Fructose 1,6-bisphosphate is formed using 1 ATP

Therefore, two ATP molecules are used to phosphorylate one 6-carbon glucose and catabolize it into two 3-carbon molecules

Two Stages in Glycolysis

2. Energy Conservation Stage:

the two 3-carbon molecules are oxidized to

generate two 3-carbon pyruvic acid molecules

Two NAD+ molecules are reduced to two

NADH molecules

4 ATP molecules are produced by substrate level

phosphorylation

net gain 2 ATP per 1 glucose

Summary of Glycolysis

1 glucose + 2 NAD+ + 2 ADP + 2P

2 pyruvic acid + 2 NADH + 2H+ + 2 ATP

11/23/2013

5

Aerobic Reactions

If oxygen supplies are adequate:

mitochondria absorb and break down pyruvic acid

molecules

Mitochondrial Membranes

Outer membrane:

contains large-diameter pores

permeable to ions and small organic molecules (pyruvic acid)

Inner membrane:

contains carrier protein

moves pyruvic acid into mitochondrial matrix

Intermembrane space:

separates outer and inner membranes

Mitochondrial ATP Production

H atoms of pyruvic acid:

are removed by coenzymes

are primary source of energy gain

C and O atoms:

are removed and released as CO2

process of decarboxylation

METABOLISM OF FRUCTOSE AND

GALACTOSE

Sucrose glucose + fructose

Lactose glucose + galactose

Metabolism of Fructose

The pathways:

Fructose 1-phosphate pathway

In liver

F F1-P (Fructokinase)

F 1-P GA + DHAP (F1-P aldolase)

GA GA3-P (glyceraldehyde kinase)

Fructose 6-phosphate pathway

F F6-P (hexokinase)

In muscle

GLYCOLYSIS

Metabolism of Galactose Galactose glucose 6-P

5 steps:

Phosphorylation of galactose to galactose 1-phospate by galactokinase

Galactose + ATP galactose-1-phosphate

Galactose-1-phosphate uridylyl transferase transfers the uridylyl group of UDP-glucose to galactose-1-phosphate to form UDP-galactose

UDP-galactose to UDP-glucose (UDP-galactose-4-epimerase)

UDP-glucose to G1P (UDP-glucose pyrophosphorylase)

Isomerization of Glu-1P to glu-6P (phosphoglucomutase)

GLYCOLYSIS

11/23/2013

6

Galactose - glucose 6-P

4 steps: Phosphorylation galactose to galactose 1-Phospate by

galactokinase Gal + ATP gal 1-P

The formation of glucose 1-Phosphate (gal 1-P uridyl transferase) galactosemia

Gal 1-P + UDP-glu - glu 1-P + UDP-gal

The epimerization of UDP-galactose to UDP-glucose (UDP-gal-4 epimerase)

Isomerization of Glu-1P to glu-6P (phosphoglucomutase)

Metabolism of Mannose

Mannose component of glycoproteins

Mannose to mannose-6-phosphate (by

hexokinase)

Mannose-6-phosphate to fructose-6-phosphate

(by phosphomannose isomerase)

LACTOSE BIOSYNTHESIS

Lactose synthesized in the mammary gland

by lactose synthase

UDP-galactose (formed by epimerization of

UDP-glucose) + glucose lactose [β-

galactosyl-(14)-glucose) + UDP