Amino acidsPlants & microorganisms

N2

NH3 or NO3-

soil bacterianitrogenase

Plants require Nitrogen in the form of ammonia or nitrate.Animals require nitrogen in the form of amino acids.

Both are dependent on soil bacteria to convert atmospheric nitrogen into useable forms.

Nitrogen-Fixing NodulesLegumes, e.g. soy beans can fix N2 –

Grains e.g. wheat/corn cannot – crop rotation

2 transamination ATP

3

catabolicOxidative deamination

Glucose

Fat

Protein translation

1anabolic

N - Cpds

Amino acidsPlants & microorganisms

N2

NH3 or NO3-

nitrogenase

RDI for protein 60g

Essential aa balance

-keto acids

COO-

|C=O |R

COO-

|C=O |CH3

Pyruvate

COO-

|C=O |CH2

|COO-

Oxaloacetate

-amino acids

COO-

|C-NH2

|R

COO-

|C-NH2

|CH3

Alanine COO-

|C-NH2

|CH2

|COO-

Aspartic Acid

Glucose

AcetylCoA

Pyruvate

NADH/FADH2

KrebsCycle

C6

C4

-ketoglutarate

C4oxaloacetate

Protein

Amino Acids

COO-

|C-NH2

|CH2

|CH2

|COO-

Glutamic acid

COO-

|C-NH2

|CH2

|COO-

Aspartic acid

Transamination

NH2

| +HOOC - CH - R

O ||HOOC - C - R

O || +HOOC - C - R

NH2

|HOOC - CH - R

Amino Transferasestransamination enzymes or transaminases

-ketoglutarate Glu and …Aspartate Aminotransferase Asp ↔ oxaloacetateAlanine Aminotransferase Ala ↔ pyruvateTyrosine Aminotransferase Tyr ↔ 4-hydroxyphenylpyruvateBranched Chain AA Aminotransferase (Leu, Ile, Val)Phosphoserine Aminotransferase

amino acid ‘X’ + -keto acid ‘Y’ ↔ amino acid ‘Y’ + -keto acid ‘X’

If the -keto acid corresponding to an amino acid is an intermediate of carbohydrate metabolism then that amino acid may be synthesized via a transamination reaction. Notable examples include Ala (pyruvate), Asp (oxaloacetate), and Glu (-keto-glutarate).

Alanine Aminotransferase Ala + -ketoglutarate ↔ pyruvate + Glu

NH2

| +HOOC - CH – CH3

O ||HOOC - C – CH2-CH2-COOH

O || +HOOC - C - CH3

NH2

|HOOC - CH - CH2-CH2-COOH

Oxidative Deamination

NH2

| HOOC - CH - CH2 - CH2 - COO-

+ NAD+ + H2O

O || HOOC - C - CH2 - CH2 - COO-

+ NADH + NH4+

Glutamate Dehydrogenase

Oxidative Deamination

(+ NAD+)

Amino Acid “X” + - Ketoglutarate

Transamination

Glutamate + - Keto Acid “X”

- Ketoglutarate + NH4+ + NADH

Glutamate Dehydrogenase

Glucose

AcetylCoA

Pyruvate

NADH/FADH2

KrebsCycle

C6

C4

-ketoglutarate

C4oxaloacetate

Protein

Amino Acids

OxidativeDeamination

Glucogenic Amino Acids

Glucogenic Amino Acids

Glucogenic Amino AcidsWill be deaminated via pyruvate or a Krebs intermediate & thus canbe converted into glucose.

Ketogenic Amino AcidWill be deaminated via AcetylCoAand thus can be made into a ketone body.

Glucose

AcetylCoA ↔ acetoacetylCoA

Pyruvate

NADH/FADH2

KrebsCycle

C6

C4

-ketoglutarate

C4oxaloacetate

LYSPHE→TYR

SuccinylCoA

fumarate

Glucogenic/Ketogenic/both

LEUTRP

ILE

ARGGLUGLNHISPRO

ALACYSGLYSERTHRTRP

ASN

ASP

PHETYR

ILEMETTHRVAL

NH3+

|- CH2 - CH - COO-

PHE

CH2 - COO-

HO - - OH

Homogentisate

NH3+

|- CH2 - CH - COO-HO -

TYR

Phe Hydroxylase

O ||- CH2 - C - COO-HO -

Tyraminotransferase

CH2 - COO-

HO - - OH Homogentisate

-OOC - CH = CH - C - CH2 - C - CH2 - COO-

|| || O O

cis

-OOC - CH = CH - C - CH2 - C - CH2 - COO-

|| || O O

trans

H ||-OOC - C = C - COO- + H3C - C - CH2 - COO-

H

O acetoacetatefumarate

Phenylalanine Hydroxylase & PKU

Phe + tetrahydrobiopterin Tyr + H2O + dihydrobiopterin

[Phe] = 0.1 mM normally 1.2 mM in PKU

1 in 20,000 homozygous1 in 150 heterozygous

IQ study: 53 93

Glucose

AcetylCoA ↔ acetoacetylCoA

Pyruvate

NADH/FADH2

KrebsCycle

C6

C4

-ketoglutarate

C4oxaloacetate

PHE phenylalanine hydroxylase

TYR

Bridging Reaction

SuccinylCoA

fumarate

PKU Xphenylpyruvate

PKU X

O O || || H3N+- CH - C - N - CH - C - O-CH3

| | CH2 CH2

| | COO-

Asp Phe

aspartame

H

Glucose

AcetylCoA

Pyruvate

NADH/FADH2

KrebsCycle

C6

C4

C5

C4

ATP

ADP O2

NAD+/FAD

oxaloacetate

Protein

Amino Acids

Ubiquitin Protein digestion (t1/2)

Ubiquitin is a protein ‘tag’ that marks another protein for proteolytic destruction

UbiquitinUbiquitin activating enzyme (E1): ubiquitin + ATP ubiquitin-AMP + PPi

Ubiquitin-conjugating enzyme (E2): attaches to activated ubiquitin via SH

Ubiquitin-protein ligase (E3): transfers ubiquitin to e-amino of target protein t1/2 & N-terminal rule (e.g. R = 2 min. M = 20 hrs.)

Proteosome: (a 26s protease complex) digests ubiquitin-tagged proteins

Slow (>20 hr.) : Ala, Cys, Gly, Met, Pro, Ser, Thr, Val

Fast (2-20 min.) : Arg, Asx, Glx, His, Ile, Leu, Lys, Phe, Trp, Tyr

Processes regulated by protein destruction gene transcription circadian rhythms inflammatory response antigen processesing tumor supression

Ubiquitin activating enzyme (E1): ubiquitin + ATP ubiquitin-AMP + PPi

Ubiquitin-conjugating enzyme (E2): attaches to activated ubiquitin via SH

Ubiquitin-protein ligase (E3): transfers ubiquitin to e-amino of target protein t1/2 & N-terminal rule (e.g. R = 2 min. M = 20 hrs.)

Urea Cycle

NH4+ + CO2 + 3ATP + Asp + 2 H2O

urea + 2ADP, Pi + AMP, PPi + fumarate

||H2N – C – NH2

O

Detoxification of ammonia