citric acid (krebs) cycle - university of massachusetts amherst

37
Citric Acid (Krebs) Cycle 2C 4C 6C CO 2 CO 2 5C 4C

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Page 1: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Citric Acid (Krebs) Cycle

2C

4C6C

CO2

CO2

5C

4C

Page 2: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 3: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 4: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 5: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 6: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Pay

Free

FreeD

eg

rad

e s

ug

ars

Syn

the

siz

e s

ug

ars

Gain

Gain Pay

Pay

Pay

Pay

Recover

Page 7: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Break ‘em down - Build ‘em up

Glycolysis

C6H12O6 + 6O2 6H2O + 6CO2

Gluconeogenesis

6H2O + 6CO2 C6H12O6 + 6O2

-686 kcal/mol

+686 kcal/mol

Page 8: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Where does all of that energy

come from?

1) NAD+ 2) ATP 3) electric aura

Gluconeogenesis

6H2O + 6CO2 C6H12O6 + 6O2

+686 kcal/mol

Page 9: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

De

gra

de

su

ga

rs

Syn

the

siz

e s

ug

ars

Sa

me

en

zym

es

Sa

me

en

zym

es

Kin

ase

s

Ph

osp

ha

tase

s

Kin

ase

(runnin

g

backw

ard

)

Tw

o k

ina

se

s

Page 10: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 11: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

De

gra

de

su

ga

rs

Syn

the

siz

e s

ug

ars

Sa

me

en

zym

es

Sa

me

en

zym

es

Kin

ase

s

Ph

osp

ha

tase

s

Kin

ase

(runnin

g

backw

ard

)

Tw

o k

ina

se

s

Page 12: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 13: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Various sugars feed

into Glycolysis

Page 14: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 15: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

21.5%

58.5% 6.5% 13.5%

Page 16: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 17: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

OH

OH

H

OH

H

OHH

OHH

O P

O-

O

O-

-D-glucose-6-phosphate

OH

OH

H

H

OHH

OHH

OH

-OP

O

O

O-

-D-glucose-1-phosphate

NH

O

ON

O

OHOH

HH

HH

OPO

O-

O-O P

O

O

O-P

O

-O

UTP

OH

OH

H

H

OHH

OHH

OH

-OP

O

O

O

NH

O

ON

O

OHOH

HH

HH

OP

O-

O

O--O P

O

O

O-P

O

-O

UDP-glucose

Page 18: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

UDP-glucose

OH

OH

H

H

OHH

OHH

OH

-O P

O

O

O

NH

O

ON

O

OHOH

HH

HH

OP

O-

O

OH

OH

H

H

OHH

OHH

OH Glycogen

OH H

H

OHH

OHH

OH

OH

OH

H

H

OHH

OHH

OH

O

-O P

O-

O

O

NH

O

ON

O

OHOH

HH

HH

OP

O-

O

Glycogen synthesis

Page 19: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Glycogen synthesis

UDP-glucose

OH

OH

H

H

OHH

OHH

OH

-O P

O

O

O

NH

O

ON

O

OHOH

HH

HH

OP

O-

O

OH H

H

OHH

OHH

OH

OH

OH

H

H

OHH

OHH

OH

O

OH H

H

OHH

OHH

OH

OH H

H

OHH

OHH

OH

O

OH

OH

H

H

OHH

OHH

OH

O

Page 20: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of Fatty AcidsBreak ‘em down

CH3(CH2)16COOH + 26O2 18H2O + 18CO2

CH3(CH2)14-CH2-CH2-COOH + 6O2

Page 21: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst
Page 22: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

O

OH

CoA SH

Will likely yield

O

CoA

S

H2O+

O

H

CoA SOH+

O

SH

CoA OH+

1)

2)

3)

Page 23: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acidsO

OH

CoA SH

OH

OH

CoA

S

O

H2O

CoA

S

ATP

ADP

O

CoA

S

3)

Fischer esterification

Page 24: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

O

H2O

CoA

S

O

CoA

S

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Hydrolysis

4) Nucleophilic attack

Page 25: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

O

H2O

CoA

S

O

CoA

S

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Hydrolysis

4) Nucleophilic attack

FAD

FADH2

Page 26: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

O

H2O

CoA

S

O

CoA

S

Which kind of enzyme would catalyze this?

1) Mutase

2) Dehydrogenase

3) Kinase

4) Isomerase

Page 27: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

O

H2O

CoA

S

O

CoA

S

Which kind of enzyme would catalyze this?

1) Mutase

2) Dehydrogenase

3) Kinase

4) Isomerase

H2C

CH2

HC

CH

Acyl-CoA dehydrogenase

Page 28: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Addition

4) Elimination

O

CoA

S

O

CoA

S

OH

Page 29: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Addition

4) EliminationCH

CH2

HC

CH

HO

O

CoA

S

O

CoA

S

OH

H2O

Trans-enoyl-CoA hydratase

Page 30: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Addition

4) Elimination

O

CoA

S

OH

O

CoA

S

O

Page 31: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Addition

4) Elimination

O

CoA

S

OH

O

CoA

S

O

CH

OH

C

O

Hydroxyacyl dehydrogenaseNAD+

NADH

Page 32: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

What kind of reaction is this?

1) Oxidation

2) Reduction

3) Addition

4) Elimination

O

CoA

S

O

CoA SH

O

CoA

S

O

CoA

S

-ketothiolase

O

O

O

H

C

O

O

O

H

Not the same

Page 33: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

O

OH

CoA SH

OH

OH

CoA

S

O

H2O

CoA

S

O

CoA

S

O

CoA

S

OH

O

CoA

S

O

CoA SH

O

CoA

S

O

CoA

S

ATP

ADP

FAD

FADH2

H2O

NAD+

NADH + H+

Oxidation (dehydrogenase)

Addition/hydration (hydratase)

Oxidation (dehydrogenase)

C18 Fatty Acid

C16 Fatty Acyl-CoA

Fischer esterification

(coupled to ATP hydrolysis)

oxidation of

fatty acids

(taking apart fatty acids,

two carbons at a time)

-ketothiolase

O

CoA

S

To Krebs Cycle

Catabolism of fatty acids

Page 34: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Catabolism of fatty acids

Page 35: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Biosynthesis of Fatty Acids

O

CoA

S

HS ACPCoA SH+

O

S ACP

O

S ACP

HS Synthase +

O

S Synthase

HS ACP

O

S Synthase

O

S ACP-O

O

+

O

S ACP

OO C O HS Synthase

(3C)(2C) (4C)

(1C)

Page 36: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

O

S ACP

O reduce reduce dehydrate

S ACP

O

O

S ACP

HS Synthase

O

S Synthase

O

S ACP-O

O

+

O C O HS SynthaseO

S Synthase

O

S ACP

O

(3C)(4C) (6C)

(1C)

Biosynthesis of Fatty Acids

from malonyl-CoA

Page 37: Citric Acid (Krebs) Cycle - University of Massachusetts Amherst

Biosynthesis of Fatty Acids

synthesis of palmitate

7 Acetyl-CoA + 7CO2 + 7ATP

7 Malonyl-CoA + 7ADP + 7Pi

Acetyl-CoA + 7Malonyl-CoA + 14NADPH + 14H+

Palmitate + 7CO2 + 8CoA-SH + 14NADP+ + 6H2O

7x(2C) 7x(1C)

(2C) primer 7x(3C)

7x(3C)

7x(1C)(14C)