Metabolisme

Protein
Saryono
Bagian Biokimia

Protein

1. Large molecules, 103 to 108amu

2. Polymers of amino acids in
specific sequences
3. Sequence determines function
4. Homo sapiens, 20 different
amino acids make up all proteins

Asam amino dan protein

Asam

amino terdiri dari gugus

karboksilat dan gugus amino
Protein tdr dari beberapa asam amino
yang terikat dengan ikatan peptide.
Ikatan peptida adalah ikatan yang
menghubungkan gugus amin dari suatu
asam amino dengan gugus karboksilat
dari senyawa asam amino yang lain

Asam amino sebagai ion dipolar

Karena

mengandung gugus karboksilat dan

gugus amino, maka dapat bersifat zwitter
ion (bermuatan +/-)
Walaupun netral, tetapi ion dipolar masih
merupakan senyawa ion
Sifat fisik: titik didih tinggi, dapat larut
dalam air, tetapi tidak larut dalam pelarut
organik
Ion dipolar bersifat amfoter, dapat
bereaksi dengan asam/basa

Berdasarkan rantai samping

Asam

amino netral:alanin, glisin,

isoleusin, leusin, metionin, fenilalanin,
prolin, triptofan, valin

Asam amino polar+nonpolar

Asam

amino basa: arginin, lisin dan

histidin
Asam amino asam: asam aspartat dan
asam glutamat

Asam amino
Semua

asam amino kecuali glisin, pada

atom C-2 terikat 4 gugus yang berbeda:
gugus karboksilat, gugus amino, atom H
dan rantai samping R
AA alifatik: Gly, Ala, Val, Leu, Ile
AA mengandung S: Cys, Met
AA mengandung gugus OH: Ser, Thr, Try
AA mengandung gugus asam : Asp, Asn,
Glu, Gln
AA mengandung cincin aromatik : His,
Phe, Tyr, Trp
AA mengandung gugus basa: Arg, Lys,
His
AA imino: Pro

Protein Types

1. Structural- provide structure

a. Collagen- tendons & cartilage
b. Keratin- hair, skin, wool, & nails
c. Spongin- sponges, Porifera
2. Contractile- movement, muscles
& filaments
a. Myosin- contractile ms filament
b. Actin- anchor ms filament

Protein Types

3. Transport- carry substances in body

a. Hemoglobin & hemocyan- transport
O2
b. Lipoproteins- transport lipids
4. Storage- store nutrients
a. Casein- stores protein in milk
b. Albumin- stores protein in eggs &
blood
c. Ferritin-stores iron in spleen & liver

Protein Types

5. Hormone- regulate metabolism &

nervous system
a. Insulin- regulates blood glucose
levels
b. Somatropin- growth hormone,
regulates growth phases

Protein Types

6. Enzyme- catalyse biochem rxn

a. Sucrase- hydrolysis of sucrose
b. Trypsin- hydrolysis of proteins
7. Protection- defense of organism
a. Immunoglobulins- stimulate
immune response
b. Venoms- poisons to kill, stun,
or discourage attackers

Enzymes

1. Protein catalysts that lower

activation energy & rxn rate of
cellular chemical reactions
required for metabolism
2. Pepsin, trypsine, sucrase,
lipases, carbonic anhydrase

Amino Acids

1. H atom, amino group, carboxyl

group, & functional group attached to
central carbon, C
2. Different functional groups
determine characteristics of individual
amino acids
3. Nonpolar aa, polar aa, acidic aa,
basic aa

Non-Essential Amino Acids in

Humans

Not required in diet

Can be formed from -keto acids by
transamination and subsequent reactions
Alanine
Asparagine
Aspartate
Glutamate
Glutamine

Glycine
Proline
Serine
Cysteine (from Met*)
Tyrosine (from Phe*)

*Essential amino acids

Essential Amino Acids in Humans

Required in diet
Humans incapable of forming requisite
carbon skeleton
Arginine*
Histidine*
Isoleucine
Leucine
Valine

Lysine
Methionine
Threonine
Phenylalanine
Tryptophan

*Essential in children, not in adults

Amino Acid Structure

amino
group

carboxyl
group

functional
group

Nonpolar Amino Acids

1. Hydrophobic aromatic group or

hydrocarbon chain
2. Glycine, alanine, valine, isoleucine,
leucine, methionine, phenylalanine,
proline, tryptophan

Polar Amino Acids

1. Hydrophilic functional groups

2. Serine, threonine, asparagine,
cysteine, tyrosine, glutamine

Acidic Amino Acids

1. Carboxylic acid on functional

group
2. Aspartic acid, glutamic acid

Basic Amino Acids

1. Amine group on functional group

2. Lysine, arginine, histidine

Essential Amino Acids

1. Ten aa are essential, must be in

diet
2. Essential- arg, his, ile, leu, lys,
met, phe, thr, trp, val
3. Ten aa can be synthesized from
essentials
4. Nonessential- ala, asn, asp, cys,
gln, glu, gly, pro, ser, tyr

Dipolar Ion

Dipolar ion- carboxyl group

donates H+ and amino grp
accepts H+
alanine,
dipolar ion

Amino Acid Ionization

1. Most aa exist as dipolar ions, net

charge = 0
2. In acid soln, carboxyl grp
accepts H+ & aa has positive
charge
3. In basic soln, amino grp donates
H+ & aa has negative charge

Peptide bond

1. Amide bond between carboxyl

grp of one aa & amino grp of
another
2. Small peptides named starting at
amino group using -yl or 3 letter
abbreviations

Tripeptide

alanylglycylserine or ala-gly-ser, a tripeptide

Aspartame

L-aspartic acid & methylesterphenylalanine

Polypeptide

1. Long chains of amino acids

2. Protein- >50 amino acids
3. Primary, secondary, tertiary, &
quaternary structure

Struktur protein

Struktur

primer;urutan/order AA dalam rantai protein

Struktur sekunder;
Alfa heliks;tulang punggung terpilin membentuk coil/ulir
Beta pleated sheet; lembaran terlipat beta
Paralel
Antiparalel

Ikatan

hidrogen, interaksi hidrofob, interaksi

elektrostatik, interaksi van der waals
Struktur tersier; lipatan/gulungan yang kompleks

Ikatan disulfida memberikan stabilitas tambahan

Struktur

kwaterner; persekutuan unit protein

Primary Structure, 1

1. Sequence of amino acids in

protein, 1o sequence determines
function
2. Thyroxine Releasing Hormoneglu-his-pro sequence
3. Insulin- two chains, 21 aa in
chain & 30 aa in chain

Secondary Structure

1. Alpha helix
2. Beta plate sheet
3. Triple helix

Alpha Helix

1. Hydrogen bonds between amino

groups & carbonyl groups twist
amino acid chain into a helix or
spiral
2. Functional groups are outside

Beta Sheet

1. Hydrogen bonds between amino

groups & carbonyl groups fold
parallel amino acid chains into
pleated sheet
2. Functional groups are on
opposite sides of sheet

Triple Helix

1. Three amino acid chains woven

into a braid
2. Structure of collagen, found in
connective tissue, skin, tendons,
ligaments

Tertiary

1. Three dimensional shape of

protein
2. Attractions & repulsions from
side groups fold protein into
specific shape
3. Globular proteins- compact &
roughly spherical, polar
4. Fibrous proteins- long & thin
fibers, structural

Quaternary

1. Two or more polypeptide units

held together by side group
interaction
2. Hemoglobin- globular, two
chains & two chains

Protein Denaturation

1. Bonds that stabilize the 2o, 3o, or

4o structure weakened or broken
2. Heat, acids, bases, certain
organic compounds, heavy metal
ions, & agitation

Amino Acid Biosynthesis

Plants and microorganisms can make all 20
amino acids and all other organisms need N
metabolites
In these organisms, glutamate is the source of N,
via transamination (aminotransferase) reactions
Mammals can make only 10 of the 20 amino
acids
The others are classed as "essential" amino acids
and must be obtained in the diet
All amino acids are grouped into families
according to the intermediates that they are
made from

Biosintesis asam amino

Vertebra

tidak dapat melakukan

biosintesis asam amino essensial
Hanya non essensial yang dapat
disintesis dari senyawa antara
amfibolik lewat lintasan metabolik
Senyawa antara : siklus asam sitrat,
alfa ketoglutarat (Glu, Gln, Pro, Hyp),
oksaloasetat (Asp, Asn), serta
senyawa bersifat glikolitik, 3fosfogliserat (Ser, Gly)
Ketiga AA lainnya (Cys, Tyr, Hyl)
dibentuk dari asam amino essensial

Glutamate-dependent transamination - primary

mechanism for amino acid synthesis

Asam amino esensial

Diabsorpsi

melalui:

Transport tergantung Na+

Difusi terfasilitasi
Transport terikat pada -glutamyl cycle

Transport tergantung Na+

Na+

di dalam sel intestinal rendah o/k

dipompa keluar ke sisi serosa oleh
pompa Na,K,ATPase
Na+ dan asam amino dipompa masuk
ke sel dari lumen intestinal
AA dibawa dengan transporter
terfasilitasi di dalam membran serosa ke
darah

-glutamyl cycle
Di

dalam ginjal dan intestinal

AA ekstrasel berreaksi dengan
glutation---menjadi -glutamyl AA
-glutamyl AA melewati membran sel
dan melepaskan AA ke dalam sel
Produk lain dikonversi kembali menjadi
glutation

Protein metabolism
8/9 Essential amino acids: must eat them!
Transamination: use the essential AA to
synthesize the others!

Protein metabolism
Another route:
Intestinal bacteria -> ammonia (toxic) ->
liver uses it to make amino acids

Protein metabolism

Amino acids: C, H, O plus amine group

with N
Healthy adult: ingest N=excrete N
(turnover of proteins!)

Protein metabolism
Amino acids are broken down into:
a) ammonia -> urea
b) pyruvate or molecules that are part of
the krebs cycle -> respired for energy, or
converted to fats or glucose

Glucogenic Amino Acids

Metabolized to -ketoglutarate, pyruvate,

oxaloacetate, fumarate, or succinyl CoA

Aspartate
Asparagine
Arginine
Phenylalanine
Tyrosine
Isoleucine

Methionine
Valine
Glutamine
Glutamate
Proline
Histidine

Alanine
Serine
Cysteine
Glycine
Threonine
Tryptophan

Ketogenic Amino Acids

Metabolized to acetyl CoA or acetoacetate

Isoleucine
Leucine
Threonine
Tryptophan

Lysine
Phenylalanine
Tyrosine

Katabolisme kerangka karbon

pada asam amino
Kalau

AA tdp melebihi kebutuhan

metabolik, kerangka karbonnya akan
dikatabolisasi menjadi senyawa antara
sebagai sumber energi, atau sebagai
substrat bagi sintesis KH, lipid
Glikogenik: Ala, Arg, Asp, Cys, Glu, Gly,
His, Hyp, Met, Pro, Ser, Thr, Val
Ketogenik: Leu
Glikogenik dan ketogenik: Ile, Lys, Phe,
Trp, Tyr

Keseimbangan nitrogen
Mengacu

pada perbedaan asupan total

nitrogen dengan kehilangan nitrogen
melalui feses, urin, keringat
Keseimbangan nitrogen positif: konsumsi
nitrogen dengan jumlah yang lebih
banyak drpd jumlah yang diekskresikan
Protein diuraikan dengan kecepatan
yang berbeda-beda
Binatang mengekskresikan nitrogen
sebagai hasil akhirnya berupa amonia,
asam urat atau urea

Siklus urea
Urea

merupakan produk akhir

katabolisme nitrogen pada manusia,
disintesis dari amonia, CO2, dan
nitrogen amida aspartat
Karena sintesis urea mengubah amonia
yang toksik menjadi urea yang non
toksik, semua defek pada sintesis urea
akan mengakibatkan intoksikasi amonia.

Kelainan pada siklus urea

Gejala

klinis: mual, muntah terhadap

makanan berprotein tinggi, iritabilitas,
letargia, retardasi mental.
Kelainan berupa : hiperamonemia,
sitrulinemia, hiperargininemia,
arginosuksinikasiduria

Defisiensi asam amino

Def.

asam amino essensial

Kwashiorkor: kadar protein plasma
rendah, edema, diare, peningkatan
resiko infeksi
Marasmus : kekurangan kalori dan
protein

Amino Acids Formed From Ketoglutarate

O

O 2 CCH 2 CH 2 CCO 2 -

Ketoglutarate

NH3 +
O 2 CCH 2 CH 2 CHCO 2

N
-

Glutamine
synthase

NH3+

H2 NCCH 2 CH 2 CHCO 2 Glutamine

CO 2 -

Glutamate

4 Steps

Transamination or
Glutamate
dehydrogenase

5 Steps

Proline
NH3 +

+
H3 NCH 2 CH 2 CH 2 CHCO 2 - Ornithine

Urea Cycle
NH2
NH3 +
+
H2 N=C-HNCH 2 CH 2 CH 2 CHCO 2 Guanidino group

Arginine

GABA Formation
-

NH3 +
O 2 CCH 2 CH 2 CHCO
Glutamate

Glutamate
decarboxylase
CO2

NH3 +
O 2 CCH 2 CH 2 CH 2
Gamma-aminobutyrate
(GABA)

GABA is an important inhibitory neurotransmitter

in the brain
Drugs (e.g., benzodiazepines) that enhance the effects
of GABA are useful in treating epilepsy

Arginine Synthesis: The Urea Cycle

-

NH3 +
O 2 CCH 2 CH 2 CHCO
Glutamate

N-Acetylglutamate
NHCOCH 3
synthase
2
O
CCH
CH
CHCO
2
2
2
2
CoASAc

N-Acetylglutamate

Activates

CPS-I

4 Steps

Carbamoyl
phosphate

NH4+ + HCO3-NH2CO2PO3-2
NH3+
NH2 CONH CH 2 CH 2 CH 2 CHCO 2 -

Ureido group

Citrulline

NH3 +

+
H3 NCH 2 CH 2 CH 2 CHCO 2 Ornithine
Ornithine
Transcarbamoylase (OTC)
(mitochondria)

The Urea Cycle (Contd.)

NH3 +
NH2 CONH CH 2 CH 2 CH 2 CHCO
Citrulline

Asp
+
NH3 -CHCH2CO 2 CO 2 -

NH3 +

+
H2 N=C-HNCH 2 CH 2 CH 2 CHCO 2 NH-CHCH2 CO 2-

Arginosuccinate
synthase

CO 2 - Arginosuccinate

Ornithine
Transcarbamoylase
(mitochondria)

NH3 +

+
H3 NCH 2 CH 2 CH 2 CHCO 2 -

Fumarate

Urea
H2NCONH2

Ornithine
Arginase

CO 2 -

Arginosuccinase

NH2

-O

2C

NH3 +

TCA Cycle

+
H2 N=C-HNCH 2 CH 2 CH 2 CHCO 2 Arginine

Urea Formation
Occurs

primarily in liver; excreted by kidney

Principal method for removing ammonia
Hyperammonemia:

Defects in urea cycle enzymes (CPS, OTC, etc.)

Severe neurological defects in neonates
Treatment:

Stop protein intake

Dialysis
Increase ammonia excretion: Na benzoate, Na phenylbutyrate, Larginine, L-citrulline

Blood Urea Nitrogen

Normal range: 7-18 mg./dL

Elevated in amino acid catabolism
Glutamate
N-acetylglutamate
CPS-1 activation
Elevated in renal insufficiency
Decreased in hepatic failure

Formation of Serine
CO 2 -

Glucose

Glycolysis

3 Steps

Dehydrogenase

H C OH

NAD+ NADH +
H+

CH2 OPO3-2

3-Phosphoglycerate

Pyruvate

Inhibits
CO 2

C=O
CH2 OPO3-2

3-Phosphohydroxypyruvate
Glutamate
Transaminase
-Ketoglutarate

H C NH3

CO 2 -

Phosphatase

CH2 OH

Serine (Ser)

CO 2 H C NH3 +
CH2 OPO3-2

3-Phosphoserine

Conversion of Serine to Glycine

H

Folate

Dihydrofolate
reductase

H 2N

CO 2 -

N
OH

C H2NHR

Tetrahydrofolate
(FH4)

Key intermediate
in biosynthesis of
purines and
formation of
thymine

H
N

N
H 2C

H C NH3 +

Serine

CH2 OH

Serine hydroxymethyl
transferase (PLP-dep.)
CO 2 -

CH2
N

N5, N10-Methylene FH4

H C NH3
H

Glycine

Important in
biosynthesis of heme,
porphyrins, and purines

Sulfur-Containing Amino Acids

NH3 +

CH 3SCH 2CH 2CHCO

Methionine
(Essential)

-Hydroxybutyrate

NH3+

HSCH 2CH 2CHCO 2 + 5-Methyl

L-Homocysteine

Cystathionine
lyase
-

HSCH 2CHCO 2

Cysteine
(Non-essential)

FH4

CO 2 -

Cystathionine
-synthase
(PLP-dep.)
NH3 +

OH

CH 3CHCH 2CO 2

- + FH4
2

Methionine
Synthase
(Vit. B12-dep.)

H C NH3 +

Serine

CH2 OH

NH3 +

SCH 2CH 2CHCO 2

CH2 CHCO2 NH3+

Cystathionine

Homocysteine
Homocysteinuria

Rare; deficiency of cystathionine -synthase

Dislocated optical lenses
Mental retardation
Osteoporosis
death
Cardiovascular disease

High blood levels of homocysteine associated with

cardiovascular disease
May be related to dietary folate deficiency
Folate enhances conversion of
homocysteine to methionine

Methionine Metabolism: Methyl

Donation

NH2
N

NH3 +

CH 3SCH 2CH 2CHCO

Methionine

S-Adenosyl methionine
synthase

-O

2 CCHCH2 CH2 -S-H2 C

NH3 +

ATP

+
H3NCH2CH2CH 2-S-H2C

CH3
OH OH

S-Adenosyl
Methionine
(SAM)

CO2
-O

CH3

NH2

NH2

Decarboxylated
SAM

OH OH

SAM
Decarboxylase
N

2 CCHCH2 CH2 -S-H2 C

N
O

NH3+

S-Adenosyl
homocysteine

OH OH

R-H

Methyltransferases

R-CH3

Polyamine Biosynthesis
NH3 +

+
H3 NCH 2 CH 2 CH 2 CHCO 2 Ornithine
(from urea cycle)

+
H3 N

N+
H

+
H3 N

CO2

H
+
N

Ornithine
decarboxylase
(ODC)
(PLP-dep.)

+
NH3

Spermine

+
NH3
Putrescine
Decarboxylated
SAM
Spermidine
synthase

Spermine
synthase

5-Methylthioadenosine
Decarboxylated
SAM

+
H3 N

5-Methylthioadenosine
H
+N
H

Spermidine

+
NH3

Polyamines

Spermidine and spermine found in virtually

all procaryotic and eucaryotic cells
Precise role undefined
Bind to nucleic acids
Inhibition of biosynthetic pathway:
CO 2 H

NH2

H2 N
CHF2

-Difluoromethylornithine (DFMO)
(Eflornithine) - inhibits ODC;
used to treat
Pneumocystis carinii infectons

Creatine and Creatinine

NH2

Arginine-glycine
transamidinase
(Kidney)

NH3 +

+
H2 N=C-HNCH 2 CH 2 CH 2 CHCO 2 -

Glycine

Arginine
H
N

Creatinine
(Urine)

+
H2 N=C-HNCH 2 CO 2 -

Ornithine

HN

Guanidoacetate

Guanidoacetate
Methyltransferase
(Liver)
Non-enzymatic
(Muscle)

N
CH3

Creatine kinase
(Muscle)

Creatine

NH2
+
H2 N=C-NCH 2 CO 2 CH3

NH2

ATP

ADP
+ Pi

SAM + ATP
S-Adenosylhomocysteine
+ ADP

NHPO3 -2

+
H2 N=C-NCH 2 CO 2 CH3
Phosphocreatine

Creatine and Creatinine

Creatine:
Dietary supplement
Used to improve athletic performance
Creatinine:
Urinary excretion generally constant;
proportional to muscle mass
Creatinine Clearance Test:
Compares the level of creatinine in urine (24 hrs.)
with the creatinine level in the blood
Used to assess kidney function
Important determinant in dosing of several drugs
in patients with impaired renal function

Histidine Metabolism:
Histamine Formation
H
N

+
NH3
CH2 CHCO 2 -

Histidine
decarboxylase

H
N

CH2 CH2NH2

Histidine

CO2

Histamine

Histamine:
Synthesized in and released by mast cells
Mediator of allergic response: vasodilation, bronchoconstriction
(H1 receptors)
H1 blockers: Diphenhydramine (Benadryl)
Loratidine (Claritin)
Stimulates secretion of gastric acid (H2 receptors)

H2 blockers: Cimetidine (Tagamet); ranitidine (Zantac)

Phenylalanine and Tyrosine

Phenylalanine
(Essential)

H2N

NH3+

H2O

HO

HN
O

HO OH

CH2CHCO 2-

NADP+
NADPH + H+

H2N

Tetrahydrobiopterin

CHCHCH 3

N
H

Phenylalanine-4Monooxygenase
(Phenylalanine
hydroxylase)

NH3 +
Tyrosine
(Non-essential)

H
H

CH2 CHCO 2O2

H
N

N
Dihydrobiopterin

HN
O

N
H

CHCHCH 3
HO OH

Phenylketonuria (PKU) Disease

Deficiency of Phe hydroxylase

Occurs in 1:16,000 live births in U.S.
Seizures, mental retardation, brain damage
Treatment: limit phenylalanine intake
Screening of all newborns mandated in all states

Tyr
Phe
Transamination

Phenylpyruvate
(urine)

CH2 CCO 2-

Catecholamine Biosynthesis

HO

HO

Tyr hydroxylase

NH3 +
CH2 CHCO 2 -

NH3+

O2

HO

CH2 CHCO 2-

HO

Tyrosine
HO

Dihydroxyphenylalanine
(DOPA)
DOPA
decarboxylase

Epinephrine
(Adrenaline)

CHCH2 NHCH3
OH
S-Adenosylhomocysteine

Catechol

Methyl
transferase

Dopamine
hydroxylase

DOPA, dopamine, norepinephrine,

and epinephrine are all neurotransmitters

CH2 CH2 NH2

Dopamine

SAM

HO

HO
HO

HO

CO2

CHCH2 NH2
OH

Norepinephrine

Brain
L-DOPABlood
in Parkinsonism
L-DOPA

L-DOPA

Dopamine

HO
CH3
HO

Blocks

CH2-C-CO2 H

Carbidopa

NHNH2

Dopamine

Parkinsonism associated with

dopamine in brain through loss of
neurons in basal ganglia.
Carbidopa + L-DOPA

Blood Brain Barrier

HO

Melanin Formation
Tyrosinase

NH3 +
CH2 CHCO 2 -

Tyrosine

HO

NH3+
CH2 CHCO 2-

HO

DOPA

Tyrosinase
Melanin
(Black polymer)

Highly colored
polymeric
intermediates

O
O

Melanin formed in skin (melanocytes), eyes, and hair

In skin, protects against sunlight
Albinism: genetic deficiency of tyrosinase

CH2 CHCO 2 +

NH3

Dopaquinone

Tryptophan Metabolism: Serotonin

Formation
+
NH3

Indole ring

+
NH3

CH2 CHCO 2 -

Trp
hydroxylase HO

N
H

Tryptophan
(Trp)

O2

CH2 CH2 NH2

CH2 CHCO 2 -

HO

Decarboxylase
N
H

5-Hydroxytryptophan

N
H

CO2

5-Hydroxytryptamine (5-HT);
Serotonin

Serotonin

Serotonin formed in:

Brain (neurotransmitter; regulation of sleep, mood, appetite)

Platelets (platelet aggregation, vasoconstriction)
Smooth muscle (contraction)
Gastrointestinal tract (enterochromaffin cells - major storage site)

Drugs affecting serotonin actions used to treat:

Depression
Serotonin-selective reuptake inhibitors (SSRI)
Migraine
Schizophrenia
Obsessive-compulsive disorders
Chemotherapy-induced emesis

Some hallucinogens (e.g., LSD) act as serotonin agonists

L-Tryptophan
Food supplement promoted for serotonin effects
L-Tryptophan disaster (1989):
Eosinophilia-myalgia syndrome (EMS)
Severe muscle and joint pain
Weakness
Swelling of the arms and legs
Fever
Skin rash
Eosinophilia
Many hundreds of cases; several deaths
Traced to impurities

Serotonin Metabolism: 5-HIAA

CH2 CH2NH2
HO

MAO

CH2CHO
HO
N
H

N
H

Serotonin

Dehydrogenase
CH2 CO 2H
HO

Carcinoid tumors:
Malignant GI tumor type
Excretion of large amounts of 5-HIAA

N
H

5-Hydroxyindole acetic
acid (5-HIAA) (Urine)

Serotonin Metabolism: Melatonin

CH2 CH2 NH2
HO

2 Steps
N
H

Serotonin

CH2CH2 NHCOCH 3
H3CO
N
H

Melatonin

Melatonin:
Formed principally in pineal gland
Synthesis controlled by light, among other factors
Induces skin lightening
Suppresses ovarian function
Possible use in sleep disorders

Tryptophan Metabolism:
Biosynthesis of Nicotinic Acid
+
NH3
CH2 CHCO 2 -

CO 2H

Several steps
N
H

Tryptophan

Nicotinic acid (Niacin)

Nicotinamide adenine
dinucleotide (NAD)