L14_1 Biochemistry 2014

8/9/2019 L14_1 Biochemistry 2014

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BIOC405 Fall 2013

Monday October 28th


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Last time:

Principles of Metabolism ATP, NADH, Creatine Phosphate

Coupled Reactions

Introduction to Glycolysis

Today:

10 steps to Glycolysis

Fate of pyruvate

2


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3

What is Glycolysis?

Uses Glucose: Corn syrup, sucrose, starch, glycogen

Only source of energy for the brain

Fuels quick bursts of activity in muscle

10 reactions

Takes place in the cytoplasm of a cell.

The oxidation of glucose to pyruvate, NADHand ATP.


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4

Glucose + 2 Pi+ 2 ADP + 2 NAD+

2 pyruvates + 2 ATP + 2 NADH + 2 H++ 2 H2O


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5


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9

aldose

ketose


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10

Phosphoglucose Isomerase Reaction 2Glucose-6-P to Fructose-6-P

Why does this reaction occur?

Next step (phosphorylation at C-1) would be tough for

hemiacetal OH but easy for primary OH

Isomerisation activtes C-3 for cleavage in aldolase reaction.


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11

Phosphofructokinase I

ATP

ADP


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12


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13Splits bond between carbons 3 and 4.

1

2

34

5

6

1

2

3

1

2

3


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14

Step 5


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Glucose

DihydroxyacetonePhosphate

Pyruvate

Glyceraldehyde 3 P

ATP

ATP

ATP

ATP

TheInvestment

Phase

Driving force for the TIM reaction is

the siphoning off of Glyceraldehyde

3 P into the final stages of glycolysis.


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Glycolysis

ADP

ATP

NAD+

NADH

+H+

Pi!G = -1.1 kJ/mol

This type of ATP production is calledSUBSTRATE-LEVEL PHOSPHORYLATION

GAPDH

PGK


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GAP + Pi + NAD+ 1,3-Bisphosphoglycerate + NADH !Go = +6.7 kJ/mol

1,3-BPG + ADP 3-Phosphoglycerate + ATP!

Go

= -18.8kJ/mol

------------------------------------------------------------------------------------------

GAP +Pi + NAD++ ADP 3PG + NADH +ATP

!G0= -12.1kJ/mol

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The process involves a2,3-bisphosphate intermediate.

Where have you seen this molecule before?????

mutases cause

intramolecular shiftof a chemical group


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Box 7-3

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8 mM

4 mM


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Respiratory Alkalosis

H2O + CO2 H2CO3

H+ + HCO3-

Bicarbonate

buffer inblood serum

To the air

lungs


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Box 15-2 figure 1

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The amount of 2,3

BPG in erythrocytes

increases when thepH of blood

increases

Bisphosphoglycerate mutase is

primarily found in erythrocytes.


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Less than normal 2,3 BPG)

More than normal 2,3 BPG)


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ADP

ATP

H2O

Substrate level phosphorylation again


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Pyruvate kinase (phosphoryl transfer).

Stryer 5/e

-16 kJ/mol -46 kJ/mol


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Glucose

DihydroxyacetonePhosphate

Pyruvate

Glyceraldehyde 3 P

ATP

ATP

ATP

ATP

TheInvestment

Phase

Driving force for the TIM reaction is

the siphoning off of Glyceraldehyde

3 P into the final stages of glycolysis.


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Glucose

DHAP

Pyruvate

Glyceraldehyde 3 P

ATP

ATP

2 ATP

2 ATPThe

Payoff

Phase

2 NADH


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Glucose + 2 Pi+ 2 ADP + 2 NAD+

2 pyruvate + 2 ATP + 2 NADH + 2 H++ 2 H2O

Problem:

A balanced equation for Glycolysis

How to regenerate NAD+?


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NAD+

needed

here:


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Anaerobic fate of

pyruvate (muscle)

Glycolysis to lactate is referred to as anaerobic glycolysis

This reaction is referred to as homolactic fermentation


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Anaerobic fate ofpyruvate (yeast)

This reaction is referred to as alcoholic fermentation

TPP


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34We also will encounter TPP in pyruvate dehydrogenase (PDH) and as

an aldehyde carrier in transketolase reactions.

Structure & Function of Thiamine Pyrophosphate.The cofactor, TPP is used as a coenzyme for decarboxylations of !-

keto acids. It is derived from thiamine (Vitamin B1) by transfer of a

pyrophosphate group from ATP to thiamine, yielding TPP and AMP.


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Anaerobic fate of

pyruvate (yeast)

This reaction is referred to as alcoholic fermentation

TPP


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Aldehyde dehydrogenase

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CH3CH2OH + NAD+ CH3CHO + H

++ NADH

CH3CHO + NAD++ H2O CH3COO-+ NADH + 2H+

ethanol acetaldehyde

acetaldehyde acetate

2 forms of aldehyde

dehydrogenase mitochondrial

and cytoplasmic

Some people (particularly Asians) have a less active form of

the mitochondrial form of aldehyde dehydrogenase.

Acetaldehyde accumulates in blood.


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Disulfiram: inhibitor of

acetaldehyde dehydrogenase

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Discovered by accident in 1948

while looking for a remedy for

parasite infections. Investigatorstried it on themselves and found

they could not drink alcohol.

Now used as a treatment foralcoholism.

Flushing of face

Headache

Nausea

Chest pain

Vomiting

Blurred vision

Mental confusion

etc....


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Some Key Concepts for Glycolysis

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Sources of energy, ATP, Phosphocreatine, glycolysis,respiration

Types of Glucose Transporters and hexokinases

Importance of coupled reactions

Overall scheme for glycolysis

10 steps of glycolysis and their significance

Investment vs. Payoff phases

Isomerase vs. Mutase

Significance of 2,3 BPG

Which steps use and which steps make ATP

How NADH is regenerated in animals vs. in yeast. How alcohol is made and how it is metabolized.

L14_1 Biochemistry 2014

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