12.09.08: Amino Acid Metabolism (Nitrogen Metabolism)

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M1 Renal: Nitrogen Metabolism (and Related Topics)

Fall 2008

• Amino Acid Metabolism (Nitrogen metabolism) • Folate Metabolism (“One-Carbon pathways”) • Nucleotide Metabolism

Dr. Robert Lyons Assistant Professor, Biological Chemistry

Director, DNA Sequencing Core Web: http://seqcore.brcf.med.umich.edu/mcb500

Supplementary study material on the Web: http://seqcore.brcf.med.umich.edu/mcb500

R. Lyons

Glu, Gln,Asp, NH3

Amino Acid metabolism Folate metabolism

Nucleic Acid metabolism

MethyleneTHF

MetCycle

Pu rin e s Py rim id in e s

Uric Acid

Urea

Amino acids

DNARNA

(energy)

TCA Cyclefumarate

oxaloacetate

R. Lyons

Protein Degradation: • Endogenous proteins degrade continuously

- Damaged - Mis-folded - Un-needed

• Dietary protein intake - mostly degraded Nitrogen Balance - expresses the patient’s current status - are they gaining or losing net Nitrogen?

Transaminases Collect Amines

General reaction overview:

C

H

R COO

NH2

aminoacid

C

H

R COO

NH2

aminoacid

(typically glutamate)

1 2CR COOO

!-ketoacid

(typicallyalpha-ketoglutarate)

(-)+ +2

CR COOO

!-ketoacid

(-)

1(-) (-)

Details of reaction mechanism:

C

H

R COO

NHC

H

R COO

N

N

CHO

CH

CH

OHOP

pyridoxalphosphate

aminoacid

+

H O2

3

2

CH

CH

CHOHOP

3

2

2

C

H

R COO

N

CHCH

CH

OHOP

3

2

+

H+

+

C

H

R COO

N

CH

CH

CHOHOP

3

2

+

CR COO

NH

CH

O

CH

CH

OHOP

pyridoxaminephosphate

+

3

2

2

+

H

!-ketoacid

(-)(-) (-) (-)

(-)

NH

NH

NH N

H

R. Lyons

NH

N

CH

CH

CH

OHOP

pyridoxaminephosphate

3

2

2

H

+

H

+ CR COOO

!-ketoacid

N

CHO

CH

CH

OHOP

pyridoxalphosphate

3

2

H

++ C

H

R COO

NH2

aminoacid

(-)

Transfer the amine back to an acceptor α-keto acid

R. Lyons

Some amino acid + α-ketoglutarate à some alpha keto acid + Glutamate

In other words, alpha-ketoglutarate is the preferred acceptor, and Glutamate is the resulting amino acid:

In peripheral tissues, transaminases tend to form Glutamate when they catabolize amino acids

Glutamate can donate its amines to form other amino acids as needed

Glutamate + oxaloacetate à α-ketoglutarate + aspartate

A specific example - production of Aspartate in liver (described a few slides from now):

Gett in g Amin es In to the L iv er

O C CH CH C

H

NH

CO

2

2 2 2 2

glutamate

NAD(P)

NAD(P)H

O C CH CH C CO2 2 2 2

!-ketoglutarate

+ NH3

ammonia

(-) (-) (-) (-)

O(mito)

C

H

OOC CH2

NH3(+)

(-)CH2COO(-)

glutamate glutamine

C

H

OOC CH2

NH3(+)

(-)CH

2C

O

NH2

NH3

ATP ADP Pi+ +

GlutamateDehydrogenase:

GlutamineSynthetase:

R. Lyons

In th e L iv er: Precursers for Urea Cycle

Glutamine is hydrolyzed to glutamate and ammonia:

C

H

OOC CH2

NH3(+)

(-) CH2C

glutamate

O

OH

glutamine

C

H

OOC CH2

NH3(+)

(-)CH2C

O

NH2

H O2 NH3

Glutamate donates its amino group to form aspartate:

Glutamate aspartateoxaloacetate

+ +

!-ketoglutarate

O C CH CH C

H

N H

CO

2

2 2 2 2(- ) (-) O CC H C

H

CO2 2 2

( -) ( -) O C CH CH C

O

C O2 2 2 2

(- ) (-) O C CH C

H

NH

CO

2

2 2 2(- ) (-)

O

Glutamate-aspartate aminotransferase:

.

.

Ammonia can also be formed by the glutamate dehydrogenase reaction and several other reactions as well.

R. Lyons

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

C a rbam oy l p h o s ph a te sy n th e ta s e I

H O C

O

O

A T P

A D P

P

N H

P

(- ) H O C

O

O

b ic ar b on at ec ar bo ny l

ph os p ha te i

3

H O C

O

N H2

ca rb a ma te

A T P

A D P

O C

O

N H2

P

ca rb a mo yl

ph os p ha te

R. Lyons

O rn ith in e T ra n s ca rb am oy las e

C

H

OO C C H2

N H3

(+ )

( -)C H

2C H

2N H3

(+ )

O rn ith in e

C

H

O O C C H2

N H3(+ )

(- )C H

2C H

2N H

2N HC

O

C it ru llin e

N H2

C

O

3O P O( -)

C arb am o y l p ho s p hateP i

C H2N H3

(+ )

R. Lyons

A rg in ino su c c in a te s yn the tas e

O CCH

C

H

NH2

2 2 2

aspartate

(-) (-)CO

C

H

OOC CH2

NH3(+)

(-)CH

2CH2NH

2NHC

O

Citrulline

iATP AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH2NH C NH

O CCH C

H

NH2

2 2 2(-) (-)CO

2(+)

Argininosuccinate

R. Lyons

A rg in in o s u cc ina te ly a se

C

H

OOC CH2

NH3(+)

(-)CH

2CH2NH NH

2CNH

2(+)

Arginine

C

H

OOC CH2

NH3

(+)

(-)CH

2CH2NH C NH

O CCH C

H

NH2

2 2 2(-) (-)CO

2(+)

ArgininosuccinateO C C C

H2 2

(-) (-)COH

Fumarate

R. Lyons

A rg in as e

C

H

OOC CH2

NH3(+)

(-)CH

2CH2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH2CH

2NH NH2C

NH2(+)

ArginineNH2 C

ONH

2

Urea

H2O

R. Lyons

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

Urea Cycle Connects to TCA Cycle

Arginine

CitrullineO CCH C

H

NH2

2 2 2

Aspartate

(-) (-)CO

Argininosuccinate

O C C CH

2 2(-) (-)CO

H

Fumarate

MalateOxaloacetate

TCA Cycle

!-Ketoglutarate

Citrate

Urea

Ornithine

Urea Cycle

R. Lyons

Gett in g Amin es In to the L iv er

O C CH CH C

H

NH

CO

2

2 2 2 2

glutamate

NAD(P)

NAD(P)H

O C CH CH C CO2 2 2 2

!-ketoglutarate

+ NH3

ammonia

(-) (-) (-) (-)

O(mito)

C

H

OOC CH2

NH3(+)

(-)CH2COO(-)

glutamate glutamine

C

H

OOC CH2

NH3(+)

(-)CH

2C

O

NH2

NH3

ATP ADP Pi+ +

GlutamateDehydrogenase:

GlutamineSynthetase:

R. Lyons

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

C P S I is S t im u la ted by N A G

H O C

O

O

A T P

A D P

P

N H

P

( -) H O C

O

O

bi ca rb o na tec a rb on y l

p ho s ph at e i

3

H O C

O

N H2

c ar ba m at e

A T P

A D P

O C

O

N H2

P

c ar ba m oy l

p ho sp h at e

g lu t am ate

C

H

O O C C H2

N H3

( +)

( - )

C H2C

O

O H+ CoA -

C

H

O O C C H2

N H

( - )

C H2C

O

O H

C O

C H3

C O

C H3

a cety l Co A N -acety l g lu t am a te(N AG )

N -a ce ty lg lu ta m a tesy n th e tase

( re pe a t in g the f igu re from pa ge 3 o f y ou r h an do u t)

R. Lyons

Muscle

Liver

Glucose Pyruvate

Alanine

Amino acids

(Amines)

!-ketoglutarate

Glutamate

Alanine

PyruvateGlucose

bloodtransport

!-ketoglutarate

Glutamate NH3

Urea

--

R. Lyons

Arginine

Amino acids:

Alanine Glutamate

Glutamine

Transamination Deaminationpurine

deamination:

NH4(+)

Glutamine

Alanine NH4(+)

Citrulline

NH4(+) Urea

Muscle:

Liver:

Intestine:

Alanine

AspartateGlu

Glutamine

NH3

Kidney:

Arginine

Citrulline

Glutamine

NH4(+)

Complicating the picture: Other tissues may be involved

R. Lyons

Why is Ammonia Toxic?

Why is Ammonia Toxic? • Possible neurotoxic effects on

glutamate levels (and also GABA)

(due to shifting equilibria of reactions involving these compounds)

Why is Ammonia Toxic? • Possible neurotoxic effects on

glutamate levels (and also GABA)

(due to shifting equilibria of reactions involving these compounds)

• Possible metabolic/energetics effects: - alpha-ketoglutarate levels - glutamate levels - glutamine

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

Defects are diagnosed based on the metabolites seenin the blood and/or urine.

CPSD

OTCD

ASD

ALD

AD

No elevation except ammonia; diagnosed by elimination.Elevated CP causes synthesis of OrotateElevated citrullineElevated argininosuccinateElevated arginine

Inherited Defects of Urea Cycle Enzymes: Diagnosis

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

C P S I is S t im u la ted by N A G

H O C

O

O

A T P

A D P

P

N H

P

( -) H O C

O

O

bi ca rb o na tec a rb on y l

p ho s ph at e i

3

H O C

O

N H2

c ar ba m at e

A T P

A D P

O C

O

N H2

P

c ar ba m oy l

p ho sp h at e

g lu t am ate

C

H

O O C C H2

N H3

( +)

( - )

C H2C

O

O H+ CoA -

C

H

O O C C H2

N H

( - )

C H2C

O

O H

C O

C H3

C O

C H3

a cety l Co A N -acety l g lu t am a te(N AG )

N -a ce ty lg lu ta m a tesy n th e tase

( re pe a t in g the f igu re from pa ge 3 o f y ou r h an do u t)

R. Lyons

Liver mitochondrion

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

(+)

Arginine

C

H

OOC CH2

NH3(+)

(-) CH2CH

2NH C

O

Citrulline

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH C

O

Citrulline

2ATP + HCO +3

NH2 C

O

3OPO(-)

Carbamoylphosphate

Pi

2ADP + Pi

O CCH C

H

2 2 2

aspartate

(-) (-)CO

i

ATP

AMP + PP

C

H

OOC CH2

NH3

(+)

(-)CH

2CH

2NH C

O CCH C

H

2 2 2(-) (-)CO

(+)

Argininosuccinate

Liver cytoplasm

O C C CH

2 2(-) (-)CO

H

Fumarate

H O2

CO

Urea

NH2

NH2

NH2

NH3

NH2

NH2

NH2

NH2

NH2NH2

1

5

4

3

2

R. Lyons

Clinical Management of Urea Cycle Defects

• Dialysis to remove ammonia • Provide the patient with alternative ways to excrete

nitrogenous compounds: • Levulose - acidifies the gut • Low protein diet

* Intravenous sodium benzoate or phenylacetate * Supplemental arginine

Ornithine

Arginine

Citrulline

i

ATP

AMP+PPArgininosuccinate

HO2

CO

UreaNH2NH2 Aspartate

Excreted by kidney

Excreted by kidney

XDietaryArginine

carbamoylphosphate

XASD

ALD

R. Lyons

Degrading the Amino Acid Carbon Backbone

Easily-degraded products after transamination:

O C CH C

H

NH3

2 2 2

aspartate

(-)COtransamination

O CCH CO

2 2 2(-)CO

oxaloacetate

(-) (-)

(+)

O C CH C

H

NH3

2 2 2

glutamate

(-)

transaminationCH C

O2 2

(-)

!-ketoglutarate

CH2

O C2

CH2

CO CO(-) (-)

(+)

CH C

H

NH3

3 2

alanine

(-)COtransamination

CH C

O3 2

(-)CO

pyruvate(+)

We also already know how to degrade Glutamine: Glutamine ----------------> glutamate + ammonia Asparagine ---------------> aspartate + ammonia

…and by analogy, how to degrade Asparagine:

glutaminase

asparaginase

glutaminase

R. Lyons

Many amino acids are purely glucogenic: Glutamate, aspartate, alanine, glutamine, asparagine,…

Some amino acids are both gluco- and ketogenic: Threonine, isoleucine, phenylalanine, tyrosine, tryptophan

Amino Acids are categorized as ‘Glucogenic’ or ‘ketogenic’ or both.

The only PURELY ketogenic Amino Acids: leucine, lysine

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH NH

2C

NH2(+)

Arginine

Urea (viathe urea cycle)

C

H

OOC CH2

NH3(+)

(-)CH

2CH

2NH3

(+)

Ornithine!-ketoglutarate

glutamate

C

H

OOC CH2

NH3

(+)

(-)CH

2C

glutamate - 5 - semialdehyde

O

H

NAD(P)

NAD(P)H

(+)

C

H

OOC CH2

NH3(+)

(-)CH

2C

glutamate

O

OH

! - ketoglutarate

NH

(+)OOC(-)

Proline

glutamine

C

H

OOC CH2

NH3(+)

(-)CH

2C

O

NH2

H O2

NH3

Amino acids with 5-carbon backbones tend to form α-ketoglutarate

R. Lyons

C

H

OOC NH3(+)

(-)

H

Glycine

NAD NADH(+)

THF N -N - methylene THF5 10

+CO NH4

(+)

2

CH

OOC NH3(+)

(-)2

GlycineTHF N -N - methylene THF5 10Serine

CHOOC NH3(+)

(-)

CH OH2

GlycineSynthase:

SerineHydroxymethyl-transferase:

Serine

CHOOC NH3(+)

(-)

CH OH2

H O2

COOC NH3

(+)(-)

CH2

COOC NH2

(+)(-)

CH3

COOC(-)

CH3

H O2

NH4

(+)

OSerine

Dehydratase:

Degradation and Biosynthesis of Serine and Glycine

R. Lyons

C

H

COOCH2

NH3

(+)

(-)CH2

Methionine

Serine

C

H

COOCH2

NH3(+)

(-)HO

SCH3

C

H

COOCH2

NH3(+)

(-)CH2

S-Adenosyl Methionine

SCH3

ATP +H O2

PPi +Pi

(+)

CH2

O

HH H

HOH OH

Adenine

C

H

COOCH2

NH3

(+)

(-)CH2

Homocysteine

HS

C

H

COOCH2

NH3(+)

(-)CH2

S-Adenosyl Homocysteine

HS(+)

CH2

O

HH H

HOH OH

Adenine

BiosyntheticMethylation

reaction

Methyl acceptor

Methylated acceptor*see examples

C

H

COOCH2

NH3(+)

(-)

Cysteine

HS

(remainder ofhomocysteine

degradedfor energy)

tetrahydrofolate

N5 methyltetrahydrofolate

Methionine Cycle And Biological Methyl Groups

R. Lyons

Phenylalanine and Tyrosine

CH2 CH COO

NH3(+)

(-)

Phenylalanine

Tetrahydrobiopterin + O2Dihydrobiopterin + H2O

CH2 CH COO

NH3(+)

(-)

Tyrosine

HO

Homogentisate

Enzyme:Phenylalaninehydroxylase

Enzyme:homogentisatedioxygenaseCH2 C COO

(-)

Phenylpyruvate

O

Phenylketonuria(no phenylalanine

hydroxylase)

(Normal path shown in black, pathological reaction shown in red)

(you don’t need to know the rest)

Deficiency: Alkaptonuria “Ochronosis”

R. Lyons

Branched Chain Amino Acids

Isoleucine Leucine Valine

CH COO(-)

NH3(+)

CHCH2CH3

CH3

CH COO(-)

NH3(+)

CHCH 2CH3

CH3

CH COO(-)

NH3(+

)

CHCH3

CH3

C COO(-)

O

CHCH2CH3

CH3

C COO(-)

CHCH 2CH3

CH3

C COO(-)

CHCH3

CH3

O O

C

O

CHCH2CH3

CH3

CCHCH 2CH3

CH3

C S-CoACHCH3

CH3

O O

NAD, CoASH+

NADH +CO

2

NAD, CoASH+ NAD, CoASH+

NADH + CO2 NADH + CO2

S-CoAS-CoA

!"KG !"KG !"KG

Glu Glu Glu

---------------- Transamination ----------------

--- Branched-chain !-keto acid dehydrogenase ---

(continues on to degradation path similar to #-oxidation of fatty acids)R. Lyons

Synthesis of Bioactive Amines

CH2 CH COO

NH3

(+)

(-)

Tyrosine

HO CH2 CH COO

NH3

(+)

(-)HO

HO

DihydroxyphenylalanineTyrosine

hydroxylase(L-DOPA)

HO

HO

CH2CH NH3

(+)

2

Dopamine

CH CH NH3

(+)

2

Norepinephrine

OH

H

HO

HO

CHCH NH

2

Epinephrine

OH

H

HO

HO

CH3

R. Lyons

N

CH2 CH COO

NH3(+)

(-) HO

N

CH2 CH COO

NH3(+)

(-)

Tryptophan 5-hydroxytryptophan

Tryptophanhydroxylase

CO2

HO

N

CH2 CH NH3(+)

Serotonin

2

PLP-dependentdecvarboxylation

NAD+


R. Lyons

CH2 CH COO

NH3(+)

(-)CH2COO

(-)

Glutamate

Glutamatedecarboxylase

(PLP-dependent )

CH2 CH NH3(+)CH2COO

(-)

!-aminobutyric acid(GABA)

2

N

NH

CH2 CH COO

NH3(+)

(-)

Histidine

Histidinedecarboxylase

(PLP-dependent )

N

NH

CH2 CH NH3(+)

Histamine

2


R. Lyons

Glutamate, aspartate, alanine, glutamine, asparagine, (proline), glycine, serine (cysteine, tyrosine)

NON-Essential Amino Acids:

Essential Amino Acids:

Arginine (!), phenylalanine, methionine, histidine, Isoleucine, leucine, valine, threonine, tryptophan, lysine

Robert Lyons Slide 5: Robert Lyons Slide 7: Robert Lyons Slide 8: Robert Lyons Slide 11: Robert Lyons Slide 12: Robert Lyons Slide 13: Robert Lyons Slide 14: Robert Lyons Slide 15: Robert Lyons Slide 16: Robert Lyons Slide 17: Robert Lyons Slide 18: Robert Lyons Slide 19: Robert Lyons Slide 20: Robert Lyons Slide 21: Robert Lyons Slide 22: Robert Lyons Slide 23: Robert Lyons Slide 24: Robert Lyons Slide 25: Robert Lyons Slide 29: Robert Lyons Slide 31: Robert Lyons Slide 32: Robert Lyons Slide 33: Robert Lyons Slide 34: Robert Lyons Slide 36: Robert Lyons Slide 38: Robert Lyons Slide 39: Robert Lyons Slide 40: Robert Lyons Slide 41: Robert Lyons Slide 44: Robert Lyons Slide 45: Robert Lyons

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12.09.08: Amino Acid Metabolism (Nitrogen Metabolism)

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Transcript of 12.09.08: Amino Acid Metabolism (Nitrogen Metabolism)