Metabolisme Protein
SaryonoBagian Biokimia
Protein1. 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 proteinAsam α amino terdiri dari gugus
karboksilat dan gugus aminoProtein 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 aminoSemua 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, IleAA mengandung S: Cys, MetAA mengandung gugus OH: Ser, Thr, TryAA mengandung gugus asam : Asp, Asn,
Glu, GlnAA mengandung cincin aromatik : His,
Phe, Tyr, TrpAA mengandung gugus basa: Arg, Lys,
HisAA imino: Pro
Protein Types1. 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 Types3. 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 Types5. Hormone- regulate metabolism & nervous system
a. Insulin- regulates blood glucose levels
b. Somatropin- growth hormone, regulates growth phases
Protein Types6. 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
Enzymes1. Protein catalysts that lower activation energy & rxn rate of cellular chemical reactions required for metabolism
2. Pepsin, trypsine, sucrase, lipases, carbonic anhydrase
Amino Acids1. 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 carboxyl
group group
functional
group
Nonpolar Amino Acids1. Hydrophobic aromatic group or hydrocarbon chain
2. Glycine, alanine, valine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan
Polar Amino Acids1. Hydrophilic functional groups
2. Serine, threonine, asparagine, cysteine, tyrosine, glutamine
Acidic Amino Acids1. Carboxylic acid on functional group
2. Aspartic acid, glutamic acid
Basic Amino Acids1. Amine group on functional group
2. Lysine, arginine, histidine
Essential Amino Acids1. 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 IonDipolar ion- carboxyl group
donates H+ and amino grp accepts H+
alanine,
dipolar ion
Amino Acid Ionization1. Most aa exist as dipolar ions, net charge = 0
2. In acid sol’n, carboxyl grp accepts H+ & aa has positive charge
3. In basic sol’n, amino grp donates H+ & aa has negative charge
Peptide bond1. 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
Polypeptide1. 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, 1o
1. Sequence of amino acids in protein, 1o sequence determines function
2. Thyroxine Releasing Hormone- glu-his-pro sequence
3. Insulin- two chains, 21 aa in chain & 30 aa in chain
Secondary Structure1. Alpha helix
2. Beta plate sheet
3. Triple helix
Alpha Helix1. Hydrogen bonds between amino groups & carbonyl groups twist amino acid chain into a helix or spiral
2. Functional groups are outside
Beta Sheet1. 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 Helix1. Three amino acid chains woven into a braid
2. Structure of collagen, found in connective tissue, skin, tendons, ligaments
Tertiary1. 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
Quaternary1. Two or more polypeptide units held together by side group interaction
2. Hemoglobin- globular, two chains & two chains
Protein Denaturation1. 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 aminoVertebra tidak dapat melakukan
biosintesis asam amino essensialHanya 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, 3-fosfogliserat (Ser, Gly)
Ketiga AA lainnya (Cys, Tyr, Hyl) dibentuk dari asam amino essensial
Glutamate-dependent transamination - primary Glutamate-dependent transamination - primary mechanism for amino acid synthesismechanism for amino acid synthesis
Asam amino esensial Diabsorpsi melalui:
Transport tergantung Na+ Difusi terfasilitasi Transport terikat pada γ-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
γ-glutamyl cycle Di dalam ginjal dan intestinal AA ekstrasel berreaksi dengan
glutation---menjadi γ-glutamyl AA γ-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!8/9 Essential amino acids: must eat them!
TransaminationTransamination: use the essential AA to : use the essential AA to synthesize the others!synthesize the others!
8/9 Essential amino acids: must eat them!8/9 Essential amino acids: must eat them!
TransaminationTransamination: use the essential AA to : use the essential AA to synthesize the others!synthesize the others!
Protein metabolism
Another route:Another route:
Intestinal bacteria -> ammonia (toxic) -> Intestinal bacteria -> ammonia (toxic) -> liver uses it to make amino acidsliver uses it to make amino acids
Another route:Another route:
Intestinal bacteria -> ammonia (toxic) -> Intestinal bacteria -> ammonia (toxic) -> liver uses it to make amino acidsliver uses it to make amino acids
Protein metabolismAmino acids: C, H, O plus amine group Amino acids: C, H, O plus amine group with Nwith N
Healthy adult: ingest N=excrete N Healthy adult: ingest N=excrete N (turnover of proteins!)(turnover of proteins!)
Amino acids: C, H, O plus amine group Amino acids: C, H, O plus amine group with Nwith N
Healthy adult: ingest N=excrete N Healthy adult: ingest N=excrete N (turnover of proteins!)(turnover of proteins!)
Protein metabolism
Amino acids are broken down into:Amino acids are broken down into:
a) ammonia -> ureaa) ammonia -> urea
b) pyruvate or molecules that are part of b) pyruvate or molecules that are part of the krebs cycle -> respired for energy, or the krebs cycle -> respired for energy, or converted to fats or glucoseconverted to fats or glucose
Amino acids are broken down into:Amino acids are broken down into:
a) ammonia -> ureaa) ammonia -> urea
b) pyruvate or molecules that are part of b) pyruvate or molecules that are part of the krebs cycle -> respired for energy, or the krebs cycle -> respired for energy, or converted to fats or glucoseconverted 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 nitrogenMengacu 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-O2CCH 2CH2CCO 2
-
NH3+
-O2CCH 2CH2CHCO 2-
NH3+O
H2NCCH 2CH2CHCO 2-
Transamination or Glutamate dehydrogenase
-Keto-glutarate
Glutamate
Glutamine
Glutamine synthase
N
H H
CO2-
+
4 Steps
Proline
NH3+
+H3NCH2CH2CH2CHCO 2
- Ornithine
5 Steps
Arginine
Urea Cycle
NH3+NH2
H2N=C-HNCH2CH2CH2CHCO 2-
+
Guanidino group
GABA Formation
NH3+
-O2CCH 2CH2CHCO 2-
NH3+
-O2CCH 2CH2CH2
Glutamate Gamma-aminobutyrate(GABA)
GABA is an important inhibitory neurotransmitterin the brainDrugs (e.g., benzodiazepines) that enhance the effectsof GABA are useful in treating epilepsy
Glutamatedecarboxylase
CO2
Arginine Synthesis: The Urea Cycle
NH3+
-O2CCH 2CH2CHCO 2-
NHCOCH3-O2CCH 2CH2CHCO 2
-
NH3+
H3NCH2CH2CH2CHCO 2-
+
NH4+ + HCO3
- NH2CO2PO3-2
Glutamate N-Acetylglutamate
Ornithine
NH3+
NH2CONH CH2CH2CH2CHCO 2-
N-Acetylglutamatesynthase
CoASAc
4 Steps
CPS-I
Ornithine Transcarbamoylase (OTC)
(mitochondria)
CitrullineUreido group
Carbamoyl phosphate
Activates
The Urea Cycle (Contd.)NH3
+
NH-CHCH2CO2-
CO2-
+H2N=C-HNCH2CH2CH2CHCO 2
-
NH3+
NH2CONH CH2CH2CH2CHCO 2-
Citrulline
Arginosuccinate
Arginosuccinatesynthase
NH3+NH2
H2N=C-HNCH2CH2CH2CHCO 2-
+
Arginine
NH3+
H3NCH2CH2CH2CHCO 2-
+
Ornithine
CO2-
-O2C
H
H
Fumarate
TCA Cycle
Arginase
H2NCONH2
UreaArgino-succinase
OrnithineTranscarbamoylase(mitochondria)
NH3-CHCH2CO2-
CO2-
+ Asp
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, L-
arginine, 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 SerineOHH
CH2OPO3-2
C
CO 2-
CH2OPO3-2
CO 2-
C=O
NH3+H
CH2OPO3-2
C
CO 2-
NH3+H
CH2OH
CO 2-
C
Glucose Glycolysis
3-Phospho-glycerate
3-Phospho-hydroxypyruvate
3-PhosphoserineSerine (Ser)
Pyruvate
Dehydrogenase
NAD+ NADH + H+
Glutamate
-Ketoglutarate
Transaminase
Phosphatase
3 Steps
Inhibits
Conversion of Serine to Glycine
N
N
N
NH2N
OH
CH2NHR
H
H
NH
N CH2
NH2C
Folate
Tetrahydrofolate (FH4)
Dihydrofolate reductase
N5, N10-Methylene FH4
NH3+H
CH2OH
CO 2-
C Serine
NH3+H
H
CO 2-
CGlycine
Serine hydroxymethyltransferase (PLP-dep.)
Key intermediatein biosynthesis ofpurines andformation ofthymine Important in
biosynthesis of heme,porphyrins, and purines
Sulfur-Containing Amino Acids
NH3+
CH3SCH2CH2CHCO 2-
NH3+
HSCH2CH2CHCO 2-
NH3+
CH2CHCO2-
NH3+
SCH2CH2CHCO 2-NH3
+
HSCH2CHCO 2-
OH
CH3CHCH 2CO2-
Methionine(Essential)
L-Homocysteine
MethionineSynthase(Vit. B12-dep.)
+ FH4
+ 5-Methyl FH4
NH3+H
CH2OH
CO 2-
C Serine
Cystathionine
Cystathionine-synthase(PLP-dep.)
Cystathioninelyase
Cysteine(Non-essential)
+
-Hydroxy-butyrate
HomocysteineHomocysteinuria• Rare; deficiency of cystathionine -synthase• Dislocated optical lenses• Mental retardation• Osteoporosis• Cardiovascular disease death
High blood levels of homocysteine associated withcardiovascular disease
• May be related to dietary folate deficiency• Folate enhances conversion of homocysteine to methionine
Methionine Metabolism: Methyl Donation
N
N N
N
O
OHOH
-O2CCHCH2CH2-S-H2C
NH2
NH3+ CH3
+NH3
+
CH3SCH2CH2CHCO 2-
N
N N
N
O
OHOH
-O2CCHCH2CH2-S-H2C
NH2
NH3+
N
N N
N
O
OHOH
H3NCH2CH2CH2-S-H2C
NH2
CH3
+
S-Adenosyl methioninesynthase
ATP
S-Adenosyl Methionine(SAM)
S-Adenosyl homocysteine
Methyl-transferases
Decarboxylated SAM
SAM Decarboxylase
CO2
Methionine
R-H
R-CH3
+
Polyamine Biosynthesis
NH3+
H3NCH2CH2CH2CHCO 2-
+
H3NH
H
HN
H
N NH3
++++
H3NNH3
++
Ornithine(from urea cycle)
Putrescine
CO2
Ornithinedecarboxylase(ODC)(PLP-dep.)
DecarboxylatedSAM
Spermidine synthase
5’-Methylthio-adenosine
H3NNH
NH3
H
+++
Spermidine
Spermine
DecarboxylatedSAM
Spermine synthase
5’-Methylthio-adenosine
Polyamines• Spermidine and spermine found in virtually all procaryotic and eucaryotic cells
• Precise role undefined• Bind to nucleic acids
• Inhibition of biosynthetic pathway:
H2NNH2
CO2H
CHF2
-Difluoromethyl-ornithine (DFMO)(Eflornithine) - inhibits ODC;used to treatPneumocystis carinii infectons
Creatine and CreatinineNH3
+NH2+
H2N=C-HNCH2CH2CH2CHCO 2-
Arginine Glycine Ornithine
Arginine-glycinetransamidinase
(Kidney)NH2
H2N=C-HNCH2CO 2-
+
Guanidoacetate
NHPO3-2
CH3
+H2N=C-NCH2CO 2
-
GuanidoacetateMethyltransferase
(Liver)
SAM + ATP
S-Adenosyl-homocysteine + ADP
Phosphocreatine
N
NH
CH3
HN
O
Creatinine(Urine) Non-enzymatic
(Muscle)
NH2
CH3
H2N=C-NCH2CO 2-
+
Creatine kinase(Muscle)
ATP
Creatine ADP + Pi
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
N
NH
CH2CHCO2-
NH3
+
N
NH
CH2CH2NH2
Histidine Histamine
Histidinedecarboxylase
CO2
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
CH2CHCO2-
NH3+
CH2CHCO2-
NH3+
HO
HN
N
NH
NH
H2N
O
H
H
CHCHCH3
HO OH
HN
N
NH
NH2N
O
CHCHCH3
HO OH
Phenylalanine(Essential)
Tyrosine(Non-essential)
Phenylalanine-4-Monooxygenase(Phenylalaninehydroxylase)
O2
H2O
+
+
NADPH + H+
NADP+
Tetrahydrobiopterin
Dihydrobiopterin
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
CH2CCO2-
O
Phe
Tyr
Transamination
Phenylpyruvate(urine)
Catecholamine Biosynthesis
CH2CHCO2-
NH3+
HO
CH2CHCO2-
NH3+
HO
HO
CH2CH2NH2
HO
HO
CHCH2NH2
HO
HO
OH
CHCH2NHCH3
HO
HO
OH
Tyr hydroxylase
O2
Tyrosine Dihydroxyphenylalanine (DOPA)
Dopamine
DOPAdecarboxylase CO2
Dopaminehydroxylase
Norepinephrine
Catechol
Epinephrine(Adrenaline)
SAM
S-Adenosyl-homocysteine
Methyl transferase
DOPA, dopamine, norepinephrine,and epinephrine are all neurotransmitters
L-DOPA in ParkinsonismBlood Brain
Blood Brain Barrier
L-DOPA L-DOPA Dopamine
Dopamine
HO
HO CH2-C-CO2H
CH3
NHNH2Carbidopa
Blocks
Parkinsonism associated with dopamine in brain through loss ofneurons in basal ganglia.Carbidopa + L-DOPA
Melanin Formation
CH2CHCO2-
NH3
O
O
+
CH2CHCO2-
NH3+
HO
HO
Highly colored polymeric
intermediates
Melanin(Black polymer)
Tyrosinase
DOPA
Dopaquinone
CH2CHCO2-
NH3+
HO
Tyrosine
Tyrosinase
Melanin formed in skin (melanocytes), eyes, and hairIn skin, protects against sunlightAlbinism: genetic deficiency of tyrosinase
Tryptophan Metabolism: Serotonin Formation
NH
CH2CHCO2-
NH3
+
NH
CH2CHCO2-
NH3
HO
+
NH
CH2CH2NH2
HO
Tryptophan(Trp)
Indole ring
Trphydroxylase
O2
5-Hydroxy-tryptophan
Decarboxylase
CO2 5-Hydroxy-tryptamine (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
• 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
L-Tryptophan
Serotonin Metabolism: 5-HIAA
NH
CH2CH2NH2
HO
NH
CH2CHO
HO
NH
CH2CO2H
HO
Serotonin
MAO
Dehydrogenase
5-Hydroxyindole acetic acid (5-HIAA) (Urine)
Carcinoid tumors: • Malignant GI tumor type• Excretion of large amounts of 5-HIAA
Serotonin Metabolism: Melatonin
NH
CH2CH2NHCOCH3
H3CO
NH
CH2CH2NH2
HO2 Steps
Serotonin 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
NH
CH2CHCO2-
NH3
+
Tryptophan
N
CO2H
Nicotinic acid (Niacin)
Several steps
Nicotinamide adenine dinucleotide (NAD)
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