Biosintesis dan katabolisme

asam amino

- Katabolisme asama amino

- Eliminasi ion amonium
- Asam amino sebagai precursor senyawa lain
 AMINO ACID BIOSYNTHESIS

• “FIXING” OF ATMOSPHERIC N2
– DIAZOTROPHS FIX N2 TO NH3
– IN MICRO-ORGANISMS, PLANTS, LOWER
ANIMALS:
• GLU DEHYDROGENASE RXN
– GLU + NAD(P)+ + H2O  -KG + NH3 + NAD(P)H + H+
– REVERSE RXN  GLU
• GLU SYNTHASE RXN’  GLU
– NADPH + H+ + GLN + -KG  2 GLU + NADP+
 Fiksasi nitrogen
2 NH3 + 3 O2 2 NO2- + 2 H2O + 2 H+

2 NO2- + O2 2 NO3-

O2 O2 O2
N2 2 NO 2 NO2- 2 NO3-

Nitrat
reduktase
NO3- + NADPH + H+ NO2- + NADP+ + H2O

Nitrat
reduktase NH4+ + 3 NADP+ + H2O + OH-
NO2- + 3 NADPH + 4 H +
 AMINO ACID BIOSYNTHESIS
• DOES THE GLU DEHYDROGENASE RXN’ WORK IN REVERSE
IN MAMMALS?
– THERE IS SOME CONTROVERSY ABOUT THIS
– THE HYPERAMMONEMIA/HYPERINSULINEMIA SYNDROME (HI/HA) IS
CAUSED BY A MUTATION IN GDH THAT  A GAIN IN FUNCTION
• SUGGESTS THAT THE PREFERRED DIRECTION IS TOWARD THE RIGHT
– DEPENDING UPON THE ORGANISM, THE GLU DEHYDROGENASE MIGHT
BE CLOSE TO EQUILIBRIUM, OR FAVORED TO THE RIGHT OR LEFT
• SO, PREFORMED -AMINO NITROGEN, IN THE FORM OF GLU,
MUST BE CONSIDERED AN ESSENTIAL NUTRIENT
 AMINO ACID BIOSYNTHESIS

• ESSENTIAL AMINO ACIDS

*ARGININE METHIONINE
HISTIDINE PHENYLALANINE
ISOLEUCINE THREONINE
LEUCINE TRYPTOPHAN
LYSINE VALINE
• NOTE
– ARG IS ESSENTIAL IN INFANTS AND CHILDREN
– MOST SYNTHESIZED ARG  ORNITHINE AND
UREA VIA THE UREA CYCLE
 AMINO ACID BIOSYNTHESIS

• NONESSENTIAL AMINO ACIDS

ALANINE GLUTAMINE
ASPARAGINE GLYCINE
ASPARTATE PROLINE
*CYSTEINE SERINE
GLUTAMATE *TYROSINE
• NOTE:
– CYS GETS ITS SULFUR ATOM FROM MET
– TYR IS HYDROXYLATED PHE
• SO IT’S NOT REALLY NONESSENTIAL
 AMINO ACID BIOSYNTHESIS
• ALL ARE SYNTHESIZED FROM COMMON METABOLIC
INTERMEDIATES
• NON-ESSENTIAL
– TRANSAMINATION OF -KETOACIDS THAT ARE AVAILABLE AS
COMMON INTERMEDIATES
• ESSENTIAL
– THEIR -KETOACIDS ARE NOT COMMON INTERMEDIATES
(ENZYMES NEEDED TO FORM THEM ARE LACKING)
• SO TRANSAMINATION ISN’T AN OPTION
– BUT THEY ARE PRESENT IN COMMON PATHWAYS OF MICRO-
ORGANISMS AND PLANTS
 COO
COO
C O glutamat
dehidrogenase
H3N CH
+ +
+ NH4 + NADPH + H + NADP+ + H2O
CH2
CH2
CH2
CH2
COO
COO
alfa-Ketoglutarat
Glutamat

COO
COO
H3N CH
H3N CH
glutamin
sintetase CH2
CH2 + + ADP + Pi
+ NH4 + ATP
CH2
CH2
C NH2
COO
O
Glutamat
Glutamin
 Biosintesis asam amino non-esensial
Alanin
aminotransferase
Piruvat + Glutamat Alanin + α-keto glutarat

Aspartat
Amino transferase
Oksaloasetat + Glutamat Aspartat + α-keto glutarat
 Piruvat Ribosa 5-fosfat

Alanin Valin Leusin Histidin

Oksaloasetat

Aspartat

Asparagin Metionin Treonin Lisin

 Α-keto glutarat

Glutamat

Glutamin Prolin Arginin

Fosfoenol piruvat +
Eritrosa-4-fosfat
3-fosfogliserat

Serin Fenilalanin Triptofan

Sistein Glisin Tirosin

Contoh proses biosintesis asam amino esential
Biosintesis glisin

H H
COO N N
COO
CH2 CH2
+H3N C H + +
H +H3N C H H

CH2OH N N CH2
CH2
H H
H2N CH2 N

Serin Tetrahidrofolat Glisin N,N-metilen

tetrahidrofolat
 Katabolisme protein
• Protein yang dikonsumsi berlebih dalam tubuh
tidak dapat dideposit, kecuali pada tanaman
• Asam amino untuk proses katabolisme dapat
berasal dari proses daur ulang protein di dalam
tubuh
• Pada keadaan kelaparan atau diabetes yang
tidak terkontrol maka protein akan terdegradasi
dan asam amino akan digunakan sebagai
sumber energi
Overview of Amino Acid Catabolism:
Interorgan Relationships

BCAA=branch chain a.a

 Overview of Amino Acid Catabolism:
Interorgan Relationships

• Intestine
– Dietary amino acids absorbed
– Utilizes glutamine and asparagine as energy
sources
• Releases CO2, ammonium, alanine, citrulline as
endproducts
• Utilizes glutamine during fasting for energy
– Dietary amino acids and catabolites released
to portal blood
 Overview of Amino Acid Catabolism:
Inter organ Relationships
• Liver
– Synthesis of liver and plasma proteins
– Catabolism of amino acids
• Gluconeogenesis
• Ketogenesis
• Branched chain amino acids not catabolized
• Urea synthesis
– Amino acids released into general circulation
• Enriched (% of total aa) in BCAA (2-3X)
 Overview of Amino Acid Catabolism:
Inter organ Relationships
• Skeletal Muscle
– Muscle protein synthesis
– Catabolism of BCAA
• Amino groups transported away as alanine and glutamine
(50% of AA released)
– Alanine to liver for gluconeogenesis
– Glutamine to kidneys
• Kidney
– Glutamine metabolized to alfa-KG + NH4
• a-KG for gluconeogenesis
• NH4 excreted or used for urea cycle (arginine synthesis)
– Important buffer preventing acidosis
– [NH4+] : [NH3] = 100 : 1
 Vitamin-Coenzymes
in Amino Acid Metabolism
• Vitamin B-6 (pyridoxal phosphate)
• Folic acid (tetrahydrofolate)
• Vitamin B-12
Disposal of Amino Acids Nitrogen:
Key reactions

• Transamination reactions
• Deamination reactions
– Glutamate dehydrogenase
– Hydrolytic deamination
• Glutaminase
• Glutamine synthesis
 Disposal of Amino Groups:
Transamination Reactions

• Often the first step of amino acid degradation

• Transfer of amino group from many amino acids
to limited number of keto acid acceptors
– Pyruvate <-> alanine
– Oxaloacetate <-> aspartate
– Alpha-keto-glutarate <-> glutamate
 Disposal of Amino Groups:
Transamination Reactions
• Transamination reactions tend to channel amino
groups on to glutamate
– Glutamate’s central role in amino acid N metabolism
 Disposal of Amino Groups:
Transamination Reactions
• Transaminase reactions are reversible
– ALT = SGOT
• ALA important in muscle where ~25% of AA-N is transported
out on ALA
• In liver, reverse reaction moves AA-N back on GLU
– AST = SGPT
• ASP important in liver since half of urea-N is from ASP
 Disposal of Amino Groups:
Deamination Reactions
• Glutamate dehydrogenase
– oxidative deamination
– Important in liver where it releases ammonia for urea
synthesis

• Hydrolytic deamination
– Glutaminase & asparaginase
 Disposal of Amino Groups:
Glutamine Synthetase

• Important plasma transport form of nitrogen from

muscle
• Detoxification of ammonia
– Brain
– Liver
• Removes ammonia intestinal tract
– Bacterial deamination of amino acids
– Glutamine utilization in intestinal cells
 Movement of amino acid nitrogen:
post-absorptive and fasting states

• From extra-hepatic tissues (muscle) to

liver
– Site of gluconeogenesis and ketogenesis
– Site of urea synthesis
• All amino acids present in plasma but
enriched (~50%) in alanine and glutamine
 Detoxification of Ammonia by the Liver: the
Urea Cycle
• Amino acid N flowing to liver as:
– Alanine & glutamine
– Other amino acids
– Ammonia (from portal blood)
• Urea
– chief N-excretory compound
The 5-carbon Krebs Cycle intermediate -
ketoglutarate is produced from arginine,
glutamate, glutamine, histidine, and
proline (p. 1001).
Glutamate deamination, via Glutamate
Dehydrogenase or Transaminase, directly
yields -ketoglutarate (at right & above).

Histidine is first converted to glutamate.

The last step in this pathway involves the
cofactor tetrahydrofolate (THF).

The aromatic amino acids phenylalanine

& tyrosine are catabolized to fumarate &
acetoacetate
 Katabolisme asam amino

Protein intraselular Protein dari diet

Asam amino bebas

Deaminasi ( proses transaminasi)

Glukosa Asam a -keto NH4+ Biosintesis

Siklus
asam sitrat
Siklus urea &
Ekaresi
Respirasi

- H2O + ATP
e + 1/2 O2 + ADP + Pi
Asam amino dan siklus asam sitrat

Alanin Leusin
Sistein Lisin
Glisin Fenilalanin
Serin Triptofan
Triptofan Tirosin

Glukosa Asetoasetil SCoA

Piruvat

Asetil SCoA
Asparagin
Aspartat
Isoleusin
Leusin
Oksaloasetat Sitrat Triptofan

Maleat
Siklus asam sitrat Isositrat

Fumarat
Fenilalanin a-keto glutarat
Tirosin Arginn
Suksinat Glutamat
Glutamin
Suksinil-SCoA Histidin
Prolin
Isoleusin
Treonin
Metionin
Valin
 Detoxification
of Ammonia by
the Liver: the
Urea Cycle
Katabolisme asam amino yang bercabang

COO COO
branch-chain O SCoA
H3N C H aminotransferase C O C

H3C CH H3C CH H3C CH

a - KG Glu
CH3 CH3
CH3
CoASH CO2
valine

COO COO
branch-chain O SCoA
H3N C H aminotransferase C O C

H3C CH H3C CH H3C CH

a - KG Glu
CH2 CH2
CH2

CH3 CH3
CH3

isoleucine
branch-chain
COO COO a = keto acid
branch-chain dehidrogenase O SCoA
H3N C H aminotransferase C O complex
C
CH2 CH2 CH2
a - KG Glu
H3C CH H3C CH H3C CH

CH3 CH3 CH3

leucine a -keto acid Derivat Asetil CoA

 Katabolisme fenilalanin dan tirosin

H NADH H
Phenylalanine
hydroxylase
CH2 C COO HO CH2 C COO

NH3 NH3
O2 H2O tyrosine
phenylalanine
aminotransferase

O
fumarate H HO CH2 C COO
OOC C C C CH2 C CH2 COO
H
acetoacetate O O p-hydroxyphenylpyruvate
4-fumarylacetoacetate

homogentisate
oxidase
OOC C C C CH2 C CH2 COO HO OH
H H
O O

4-maleylacetoacetate CH2 COO

homogentisate
Eliminasi ion amonium

NADH + H+ + NH4+
Asam amino Ketoglutarat

Glutamat dehidrogenase
Aminotransferase

NAD+ + H2O
Asam a -keto Glutamat

OH
C N
O NH4+ N C
C OH
C C
C HO N N
H
H2N NH2 Ion amonium uric acid
(enol form)
Urea
 Sintesis pigmen kulit dari tirosin

O2 H2O
HO
H
H
HO CH2 C COO
HO CH2 C COO
Tirosinase
NH3
NH3
tyrosine Dopa
O2

Tirosinase

H2O

O
H

Polimeric O CH2 C COO

Black Melanine NH3

Dopaquinone

O HO HO
Tirosinase

O N COO HO N HO N COO
H H
2H2O 2O2 CO2 H

Indole-5,6-quinone 5,6-Dihydroxyindole Leucodopachrome

Tirosin sebagai precursor senyawa amina biologis
O2 H2O HO
H H

HO CH2 C COO HO CH2 C COO

Tirosinase
NH3 NH3

Tyrosine Dopa

CO2

HO
H

HO CH2 C H

NH3
O2
Dopamin

HO HO H2O
H H
HO CH C H HO CH C H
OH NH2 CH3 OH NH3
SAH SAM
Epinephrine Norepinephrine

I I
H
HO O CH2 C COO
NH3
I I
Thyroxine
Degradasi purin dari AMP-siklis menjadi asam urat dan urat

NH2 O O

C C N C N
N HN C HN C
N C
CH CH CH
HC C HC C HC C
N N N N
N N
H
Ribose P Hypoxanthine
Ribose P
AMP HMP
xanthine
oxidase
O O
H
C N C N
HN C HN C
C O CH
C C xanthine C C O
O N N N N
H oxidase O H
H H C
uric acid
Xanthine HN
(keto form)
N
HC
N N
H
OH OH Allopurinol
H
C N C
N C N
N C
C OH C O
C C C C
HO N N N
H HO N
H
uric acid urate
(enol form)