role of amino acids protein monomeric units energy source precursors of other biological molecules...

بيوشيمي عموميگروه علوم دامي دانشکده کشاورزي

دانشگاه ياسوجدکتر مختار خواجوی

Amino Acid Metabolism

Role of Amino Acids

• Protein monomeric units• Energy source• Precursors of other

biological molecules

3

In Mammals

Plants and bacteria can

produce all

of them

Amino acids are precursors

4

Amino acids are precursors

5

SOURCE OF EACH ATOM IN THE PURINE RING

N

N

N

N

9

1 8

7 6

5

4

3

2

Glycine

N10-Formyl-FH4

N10-Formyl-FH4

Aspartate (amine)

CO2

Glutamine (amide)

N

N

2

1

3

4

5

6

Aspartate

CO2

Glutamine

SOURCES OF THE ATOMS OF THE PYRIMIDINE RING:

8

Biosynthesis of Amino Acids

The nitrogen cycle

9

Biosynthesis of Amino Acids

Nitrogen Fixation -> Microorganism

10

Major Ammonium ion carrier

Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine

11

Biosynthesis of Amino Acids

12

Biosynthesis of Amino Acids in Bacteria and Plants

Essential ones are in bold letters

13

Biosynthesis of Amino Acids in Bacteria and Plants

14

Biosynthesis of Amino Acids: Transaminations

Amino Acid1 + a-Keto Acid2 Amino Acid2 + a-Keto Acid1

NH3+

-O2CCH2CH2CHCO2-

Glutamate

OR-CCO 2

-+

O-O2CCH2CH2CCO 2

-

a-Ketoglutarate

NH2

R-CHCO 2-

+

Pyridoxal phosphate (PLP)-Dependent Aminotransferase

Products of Amino Acid Breakdown

•Glucogenic–Pyruvate–a-

Ketoglutarate–Succinyl-CoA–Fumarate–Oxaloacetate

•Ketogenic –Acetyl-CoA–Acetoacetate

Animals cannot carryout net synthesis of precursors of

gluconeogenesis from acetyl-CoA or acetoacetate

17

Amino Acid Metabolism

18

Fate of the C-Skeleton of Amino Acids

19

Fate of the C-Skeleton of Amino Acids

20

Fate of the C-Skeleton of Amino Acids

Aromatic amino acids need oxygenases + O2

21

Fate of Nitrogen in Different Organism

Classification of Organisms(Nitrogen Excretion Patterns)

• Ammonotelic: ammonia excreting

• Ureotelic: urea excreting• Uricotelic: uric acid excreting

Overall Urea Cycle(Liver)

NH3 + HCO 3– +

H2NC

NH2

O

H3N C COO–

H2C

H

COO–

3ATP 2ADP + 2P i + AMP + PP i

+HC COO–

CH–OOC

Aspartate Urea Fumarate

+

Carbamyl Phosphate Synthetase (CPS)

•CPSI (Mitochondria)–Uses NH3

–Urea Cycle•CPSII (Cytosol)

–Uses Glutamine–Pyrimidine Biosynthesis

Carbamyl Phosphate Synthetase (CPS)

Mechanism

Activation of HCO3– by ATP

HO C

O

O–

Bicarbonate (CO2)

+ –O P

O

O–

O ADP

ADP

HO C

O

OP

Carbonyl-P

Displacement of Phosphate by NH3

HO C

O

OP + NH3

Pi

H2N C

O

O–

CarbamateCarbonyl-P

Phosphorylation of Carbamate by ATP

H2N C

O

O–

ATP ADP

H2N C

O

OP

Carbamyl PhosphateCarbamate

Ornithine Transcarbamylase (OTC)

(Mitochondrion)

H2N C

O

OP + +H3N C COO–

H

(CH2)3

NH3+

Ornithine

Pi

+H3N C COO–

H

(CH2)3

NH

CO NH2

CitrullineCarbamoyl P

Non-standard amino acids (not present in proteins)

Citrulline Carrier(Ornithine Antiport)

Argininosuccinate Synthetase(Cytosol)

+H3N C COO–

H

(CH2)3

NH

CO NH2

Citrulline

+ C+H3N COO–

H

H2C COO–

Aspartate

ATP AMP + PP i

+H3N C COO–

H

(CH2)3

NH

CH2N

H N C

H

COO–

H2C COO–

Argininosuccinate

Mechanism

+H3N C COO–

H

(CH2)3

NH

CO NH2

Citrulline

CH2N COO–

H

H2C COO–

Aspartate

+H3N C COO–

H

(CH2)3

NH

CH2N

H N C

H

COO–

H2C COO–

Argininosuccinate

AMP P P

PPi

+H3N C COO–

H

(CH2)3

NH

CO NH2AMP

Citrullyl-AMP

AMP

+

Activation of oxygen atom as a leaving group

33

Ammonium Ion is Converted into Urea

Urea cycle

34

The Urea Cycle is Linked to the Citric Acid Cycle

NH4+