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Metabolisme Protein

SaryonoBagian Biokimia

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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

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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

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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

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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

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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

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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

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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

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Protein Types5. Hormone- regulate metabolism & nervous system

a. Insulin- regulates blood glucose levels

b. Somatropin- growth hormone, regulates growth phases

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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

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Enzymes1. Protein catalysts that lower activation energy & rxn rate of cellular chemical reactions required for metabolism

2. Pepsin, trypsine, sucrase, lipases, carbonic anhydrase

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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

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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

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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

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Amino Acid Structure amino carboxyl

group group

functional

group

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Nonpolar Amino Acids1. Hydrophobic aromatic group or hydrocarbon chain

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

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Polar Amino Acids1. Hydrophilic functional groups

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

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Acidic Amino Acids1. Carboxylic acid on functional group

2. Aspartic acid, glutamic acid

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Basic Amino Acids1. Amine group on functional group

2. Lysine, arginine, histidine

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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

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Dipolar IonDipolar ion- carboxyl group

donates H+ and amino grp accepts H+

alanine,

dipolar ion

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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

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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

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Tripeptide

alanylglycylserine or ala-gly-ser, a tripeptide

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Aspartame

L-aspartic acid & methylesterphenylalanine

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Polypeptide1. Long chains of amino acids

2. Protein- >50 amino acids

3. Primary, secondary, tertiary, & quaternary structure

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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

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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

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Secondary Structure1. Alpha helix

2. Beta plate sheet

3. Triple helix

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Alpha Helix1. Hydrogen bonds between amino groups & carbonyl groups twist amino acid chain into a helix or spiral

2. Functional groups are outside

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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

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Triple Helix1. Three amino acid chains woven into a braid

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

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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

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Quaternary1. Two or more polypeptide units held together by side group interaction

2. Hemoglobin- globular, two chains & two chains

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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

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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

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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

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Glutamate-dependent transamination - primary Glutamate-dependent transamination - primary mechanism for amino acid synthesismechanism for amino acid synthesis

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Asam amino esensial Diabsorpsi melalui:

Transport tergantung Na+ Difusi terfasilitasi Transport terikat pada γ-glutamyl cycle

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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

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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

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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!

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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

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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!)

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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

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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

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Ketogenic Amino Acids Metabolized to acetyl CoA or acetoacetate

• Isoleucine• Leucine• Threonine• Tryptophan

• Lysine• Phenylalanine• Tyrosine

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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

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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

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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.

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Kelainan pada siklus urea Gejala klinis: mual, muntah terhadap

makanan berprotein tinggi, iritabilitas, letargia, retardasi mental.

Kelainan berupa : hiperamonemia, sitrulinemia, hiperargininemia, arginosuksinikasiduria

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Defisiensi asam amino Def. asam amino essensial Kwashiorkor: kadar protein plasma

rendah, edema, diare, peningkatan resiko infeksi

Marasmus : kekurangan kalori dan protein

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

+

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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

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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

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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

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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

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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)

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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

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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)

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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

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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

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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

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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

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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

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• 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

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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

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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

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Tryptophan Metabolism:Biosynthesis of Nicotinic Acid

NH

CH2CHCO2-

NH3

+

Tryptophan

N

CO2H

Nicotinic acid (Niacin)

Several steps

Nicotinamide adenine dinucleotide (NAD)