Lecture 16

Glycolysis II

Glycolysis & Human

Before Step 1 of Glycolysis:

Glucose Glycolysis, Step 1 Transporter (Malfunction is related to Diabetes) Cytoplasm

OH
H O H H H OH OH

1. First of three irreversible steps

HO HO

Inherited Diseases: ATP 2+ Hexokinase Kinase (Step Highly negative G 3. Requires Mg Deficiency of Phosphoglycerate 7) (HK) ADP Deficiency of Pyruvate Kinase (Step 10) 2H OPO3 Inability of exercise due to muscle pains
H O HO HO H H H OH OH

2. Phosphate in all intermedaites

D-Glucose

Glucose-6-Phosphate (G6P)

Arsenate Poisoning
Arsenate (AsO43-) is structural analog of inorganic phosphate Pi (HPO42-) Competes with phosphate for binding site in glyceraldehyde 3-phosphate dehydrogenase (Step 6) Very unstable!

Questions & Answers

Question: What is the net outcome per molecule of glucose during glycolysis?

1. 2. 3. 4.

2 ATP consumed; 4 ATP produced; 2 pyruvate produced 4 ATP consumed; 2 ATP produced; 2 pyruvate produced 2 ATP consumed; 4 ATP produced; 1 pyruvate produced 4 ATP consumed; 2 ATP produced; 1 pyruvate produced

Question: Why is the PFK-1 step of glycolysis called the first committed step?
1. 2. 3. 4. 5. It is the first regulated step of the pathway. It is the only metabolically irreversible step. It is the first step through which all hexoses entering the pathway must pass. It is the step bridging the hexose and triose phases. It is the first step to produce ATP.

Question: Which is true about the four isozymes of hexokinase?

1. 2. They all have approximately the same Km value. Hexokinases I and II catalyze the reverse of the reaction catalyzed by hexokinases III and IV. All four hexokinases are usually saturated at normal blood glucose concentrations. Hexokinase I is active mostly in the liver. Hexokinase IV has a much higher Km than the others.

3.
4. 5.

More Questions:
1. What are the three irreversible steps of glycolysis?

2. The product of aldolase is dihdroxyacetone phosphate and ______. Give name and chemical structure.

Fate of Pyruvate,

Horton Chapter 11.3

The Fate of Pyruvate

10 Steps of Glycolysis (See Lecture 11)

Animals, Plants & many Microbes under aerobic conditions (see later)
Citric Acid Cycle

CO2 H2O

The Fate of Pyruvate

Anaerobic: Fermentation to Ethanol in yeast & some bacteria

Precursor in Gluconeogenesis
Anaerobic: Fermentation to Lactate in exercising muscles, red blood cells and lactic acid bacteria

Fermentation
In the absence of aerobic respiration
(=membrane-associated electron transport system, see later)

Fermentation regenerates NAD+ (Oxidizes NADH to NAD+) If NAD+ would not be regenerated glycolysis would stop!

Glyceraldehyde 3-phosphate NAD+ NADH + H+ 1,3-bisphosphoglycerate ~

Step 6: The addition of a phosphate

group is coupled to an oxidation, generating NADH and a high-energy phosphate bond.

~
~ ~ 3-phosphoglycerate

Step 7: ATP is produced by

substrate-level phosphorylation.

Step 8: A chemical
2-phosphoglycerate
H2O Phosphoenolpyruvate ~ ~ ~ Pyruvate rearrangement occurs.

Step 9: Water is removed, causing

the phosphate bond to become high-energy.

Step 10: ATP is produced by

substrate-level phosphorylation.

Reoxidation of NADH during alcoholic Fermentation

In yeast & some bacteria (Zymomonas)

Reoxidation of NADH during alcoholic Fermentation

In yeast & some bacteria (Zymomonas)

Hangover

Production of alcoholic beverages (beer & wine) and bread

THE OVERALL REACTION

Glucose + 2 ADP3- + 2 Pi2- + 2 H+

2 Ethanol + 2 CO2 + 2 ATP4- + 2 H2O

Auto-Brewery Syndrome
Consumption of carbohydrate-rich foods (sugar) the patient appears drunk Ethanol production in the gut by yeast

Caused by infection (e.g. antibiotic poisoning)

Reoxidation of NADH during Lactic Acid Fermentation

in exercising muscles, red blood cells, and lactic acid bacteria (Streptococcus, Lactobacillus)

Exercise Tooth decay Cheese, Yogurt, Sauerkraut, Pickles

THE OVERALL REACTION

Glucose + 2 ADP3- + 2 Pi2-

2 Lactate- + 2 ATP4- + 2 H2O

Alligator:
Quick burst of energy by lactic acid fermentation Generate ATP in the muscle quickly without O2
Needs long recovery to clear excess lactate (source of sourness after exercise)

The Pasteur Effect

Facultative microbes have both fermentation and aerobic respiration With O2 - Consumes less glucose Without O2 - Consumes more glucose

Summary
Under anaerobic conditions: Pyruvate Ethanol & CO2 or Pyruvate Lactate Both processes regenerate NAD+ from NADH.