Regulasi Metabolisme
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METABOLISME GALAKTOSAMETABOLISME GALAKTOSA
� Galaktosa berasal dari hidrolisis laktosa di dalamintestinum
� Galaktosa oleh galaktokinase akan dirobah menjadigalaktosa 1 fosfat (enzim yang Km nya < Km Heksokinase )
� Galaktosa 1 fosfat bereaksi dengan UDPGlcmembentuk UDPGal dan glukosa 1 fosfat
� Disini galaktosa dipindahkan ke pada posisi UDPGlcuntuk menggantikan glukosa oleh enzim galaktosa 1 fosfat uridil transferase
� Bagian galaktosa dari UDPGal kemudian mengalamiepimerasi oleh UDP -galaktosa 4- epimerase
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METABOLISME GALAKTOSAMETABOLISME GALAKTOSA
� Ringkasan reaksi yang dikatalisis ketiga enzim diatasGalaktosa + ATP Glukosa 1 fosfat + ADP + H+
� Glukosa 1 fosfat yang dibentuk dari galaktosa, mengalami isomerisasi menjadi glukosa 6 fosfatoleh fosfoglukomutase
� Dalam sintesis laktosa, di kelenjar mamae, glukosadiubah menjadi UDPGal oleh enzim epimerase diatas
� UDPGal mengadakan kondensasi dengan glukosamenghasilkan laktosa oleh kerja laktosa sintase
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DefisiensiDefisiensi enzimenzim dalamdalam lintasanlintasan galaktosagalaktosa
� Galaktosemia : ketidak mampuan memetabolismegalaktosa
� Terjadi akibat defek bawaan pada enzimgalaktokinase, uridil transferase atau 4 epimerase
� Defisiensi uridil transferase yang paling dikenalmenyebabkan galaktosemia
� Galaktosa yang meningkat di dalam darah, di dalammata akan dikatalisir oleh aldosa reduktase menjadipoliol ( galaktiol)
� Penumpukan senyawa ini akan menyebabkan katarak.
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REGULASI METABOLISME
Tujuan metabolisme :
�Menghasilkan ATP
�Menghasilkan bahan-bahan untukbiosynthese
�ATP diperoleh dari proses Oksidasi(Asam amino, Glukose, Asam lemak)
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� Metabolic pathways fall into three categories:
� Anabolic pathways : involved in the synthesis of compounds such as protein.They are endergonic.
� Catabolic pathways : involved in the breakdown of larger molecules, commonly involving oxidative reactions , they are exergonic, producing reducing equivalents and mainly via the respiratory chain,ATP.
� Amphibolic pathways : occur at the “crossroads “ of metabolism, acting as links between the anabolic and catabolic pathways, eg the citric acid cycle.
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Metabolism carbohydrate
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Lipid Metabolism
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Metabolism Amino Acid
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REGULASI METABOLISME
�ATP :
� Kontraksi otot
� Transport aktif
� Transduksi signal
� Reaksi biosynthese
�Acetyl Co-A CO2, NADH, FADH2
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REGULASI METABOLISME
�Contoh bahan-bahan yang dihasilkan :
- NADPH (donor elektron)
- Dihydroxyacetonphosphat(Glycerol)
- Acetyl CoA (Asam lemak, Cholesterol)
- Succinyl CoA (Porphyrin)
- Ribose- 5 Phosphat (Nucleotida)
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REGULASI METABOLISME
�Key-Enzym kecepatan prosesanabolisme dan katabolisme : kontrolmetabolisme yang efektif
� ENZYM : - mekanisme feedback (Allosterik)
- modifikasi kovalent
- proteolitik
- jumlah enzym
- kompartementasi enzym
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REGULASI METABOLISME
Kompartementasi enzym :
�Matrix mitochondria : Siklus Krebs, Phosphorilasi oksidatif, β-Oksidasi, Synthese badan keton
�Cytosol : Glycolysis, Pentose PhosphatCycle, Synthese Fatty Acid
�Keduanya : Gluconeogenesis, Urea Cycle
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REGULASI METABOLISME
�Glycolysis : Fructose 6-phosphat
ATP ATP
Citrat Phosphofructokinase
AMP ADP
F2,6 BP Fructose 1,6-bisphosphat
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REGULASI METABOLISME
� Pentose Phosphat Cycle :
Glucose 6-phosphat
NADP+
G6Pdehydrogenase
NADPH
6-Phosphoglucono-δ-lacton
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REGULASI METABOLISME
�Gluconeogenesis :
Fructose 1,6-bisphosphat
Citrat H2O
AMP Fructose 1,6-F2,6 BP bisphosphatase
Pi
Fructose 6-phosphat
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REGULASI METABOLISME
�TCA Cycle :
1. Citrat synthase
2. Isocitrat dehydrogenase
3. α-Ketoglutarat dehydrogenase
ATP aktivitas enzim
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� Acetyl CoA
Oxaloacetate Citrate
Malate Isocitrate
CO2Fumarate α Ketoglutarat
CO2
Succinate Succinyl Co A
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REGULASI METABOLISME
� Synthese Asam Lemak :
Acetyl- CoA
HCO3- + ATP
Citrat Acetyl-CoA-
Palmityl- CoA carboxylase
ADP + Pi Malonyl - CoA
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REGULASI METABOLISME
�Metabolisme Glykogen :
�Polymer dari Glukosa (UDP-Glu)
� Synthase dan Phosphorilase yang dikoordinir oleh hormon
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REGULASI METABOLISME
� Glucose 6-phosphat, berasal dari :
- mobilisasi glikogen
- pyruvat (melalui gluconeogenesis)
- asam amino glukogenik
� Pyruvat, berasal dari :
- glucose 6-phosphat
- katabolisme alanin
- laktat (melalui oksidasi di hepar)
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REGULASI METABOLISME
� Pyruvat :- di mit. Pyruvat dikarboksilasi menjadiOxaloacetat
- di cyt. Oxaloacetat didekarboksilasiphosphorilasi menjadiPhosphoenolpyruvat
� Acetyl- CoA, berasal dari :- pyruvat (melalui dekarboksilasioksidatif)
- proses β-oksidasi asam lemak- asam amino ketogenik
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REGULASI METABOLISME
Glucose
Glucose 6-phosphat
Glucose 1-P Fructose 6-P 6-Phosphogluconat
Glykogen Pyruvat Ribose 5-P
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REGULASI METABOLISME
Glucose 6-P Lactat
Pyruvat
Oksaloacetat AlaninAcetyl- CoA
3 Hydroxy-3 methylglutaryl CoA FA
CO2
Cholesterol Badan Keton
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REGULASI METABOLISME
Pyruvate Amino acids Fatty acids
Acetyl- CoA
TCA Cycle Ketone bodies Sterols and
fatty acids
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REGULASI METABOLISME
Glucose
Glycolysis
Pyruvate
Transamination Carboxylation Oxidative Reduction
decarboxylation
Alanine Oxaloacetate Acetyl-CoA Lactate
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Bersambung…
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Starve-feed cycle
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In the well-fed state, diet supplies the energy requirements.
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In the early fasting state hepatic glycogenolysis is an important source of blood glucose.
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Fasting state requires gluconeogenesisfrom amino acids and glycerol
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In early refed state, fat is metabolized normally and normal glucose metabolism is slowly reestablished
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Glucose Homeostasis
� Phase I : well fed state, in which glucose is provided by dietary carbohydrate.
� Phase II : once the supply is exhausted, hepatic glycogenolysis is used to maintain blood glucose.
� Once the supply of glucose starts to decreased,hepatic gluconeogenesisfrom lactate,glycerol and alanin takes place.
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� Phase III : gluconeogenesis is the major source of blood glucose. ( these changes happen within 20 hours of fasting)
� Phase IV : Dependence on gluconeogenesis decrease. Ketonebodies high enough concentration to enter the brain and meet some of its energy needs.
� Renal gluconeogenesis takes place.
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� Phase V : energy needs of almost every tissue were supply by either fatty acids or keton body oxidation. ( after long starvation of extremly obese patient)
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Source of Blood Glucose
- Digestion and absorption of
carbohydrates
- Glycogenolysis process
- Gluconeogenesis process
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Glucose
Blood glucose is important
� Normal [glucose]: 70-110 mg/dl
� High [glucose] (>140 mg/dl
� Low [glucose] (<60 mg/dl)
� HbA1C
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GLUCOSURIA
�� ReabsorptionReabsorption of glucose is linked to the of glucose is linked to the provision of ATP in the tubular cellsprovision of ATP in the tubular cells
� Normal, the concentration of blood glucose in individual humans is within the range 4,5 -5,5 mmol/L
→→RearpsorptionRearpsorption rate : 350 mg/min.rate : 350 mg/min.� When the blood glucose rise to relatively high
level, the kidney exerts a regulatory effect� The glomerular filtrate may contain more
glucose than can be reabsorbed
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GLUCOSURIA
� The excess passes into the urine to produce Glucosuria
� Normal individual : glucosuria occurs when the venous blood glucose concentration :
> 9,5 – 10 mmol/l
� This is termed Renal Treshold for glucose
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DiskusiDiskusi RegulasiRegulasi MetabolismeMetabolisme
�� GLUCONEOGENESIS :GLUCONEOGENESIS :
�� PyruvatePyruvate carboxylasecarboxylase ((mtmt):):
�� ATP, Biotin, COATP, Biotin, CO2 2 , Mg, Mg++++
�� PyruvatePyruvate OxaloacetateOxaloacetate
�� PhosphoenolpyruvatePhosphoenolpyruvate carboxykinasecarboxykinase ((cytcyt):):
�� GTP or ITPGTP or ITP
�� Glucose 6 Glucose 6 PhosphatasePhosphatase ::
�� Present in liver and kidneyPresent in liver and kidney
�� Absent from muscle and adipose tissueAbsent from muscle and adipose tissue
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DiskusiDiskusi RegulasiRegulasi MetabolismeMetabolisme
�� GalactoseGalactose is required in the formation of is required in the formation of Lactose, Lactose, GlycolipidsGlycolipids ((cerebrosidescerebrosides), ), ProteoglycansProteoglycans and and GlycoproteinsGlycoproteins..
�� Glucose Glucose is the precursor of all Amino sugars is the precursor of all Amino sugars ((HexosaminesHexosamines), which will be a components ), which will be a components of of GlycoproteinsGlycoproteins, , GlycosphingolipidsGlycosphingolipids, , GlycosaminoglycansGlycosaminoglycans..
�� Amino sugars : Amino sugars : GlucosamineGlucosamine, , GalactosamineGalactosamine, , MannosamineMannosamine, , SialicSialic acid.acid.
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Proteoglygans
� Core protein yang mempunyai banyakkarbohidrat yaitu Glycosaminoglycans(GAG) dengan ikatan N- atau O-Glykosida. (sampai 95%)
� Elastisitas jaringan, misalnyafleksibilitas dan kekuatan jaringantulang rawan.
� Dermatan sulfat, Heparan sulfat dll.� Berikatan dengan protein extraselluler spt fibronectin, laminin, collagen dan elastin.
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Glycoproteins
� Protein yang berikatan secaracovalent dengan karbohidrat (1-85% dari berat total)
� Ikatan : N-acetylglucosamine(GlcNAc) dengan Asn atau N-acetylgalactosamine (GalNAc) dengangugus OH dari Ser atau Thr.
� Contoh : Ceruloplasmin, Transferrin, Faktor pembekuan darah, Glycophorin, Hormone (FSH, hCG), IgA, IgM, IgG
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Glycoproteins
� Fungsi : melindungi dari denaturasi, proteolytic, antifreeze glycoprotein
� Pengenalan antar molekul : cell-cell, cell-virus, cell –molecule. Contoh : Reseptor Insulin, GLUT, gp120 (HIV)
� Molekul perlekatan sel (CAM) : Sialicacid, ICAM, LFA, Selectin, Integrin.
� Perobahan pada gugus karbohidrattsb : peradangan hebat, sel kanker.