METABOLISME

YENI VERA, S.Si, M. Biomed

 REGULASI METABOLISME

Tujuan metabolisme :
 Menghasilkan ATP
 Menghasilkan bahan-bahan untuk
biosynthese
 ATP diperoleh dari proses Oksidasi
(Asam amino, Glukose, Asam lemak)
 REGULASI METABOLISME

 ATP :
 Kontraksi otot
 Transport aktif
 Transduksi signal
 Reaksi biosynthese
 Acetyl Co-A CO2, NADH, FADH2
 Energy Producing
 System
Energy Utilizing
 ATP : penghubung ke 2 system tsb
 Energy tidak ada yang terbuang, hanya
berpindah ataupun berubah bentuk (energy
kimia panas atau mekanik)
 Reaksi yang berlangsung dalam tubuh :
- membutuhkan energy
- menghasilkan energy
 ATP

Energy production
KH Energy utilization
Lipid Biosynthesis
Protein macromolecules
Muscle contraction
Active ion transport
Thermogenesis
ADP + Pi
 REGULASI METABOLISME

 Contoh bahan-bahan yang dihasilkan :

- NADPH (donor elektron)
- Dihydroxyacetonphosphat
(Glycerol)
- Acetyl CoA (Asam lemak,
Cholesterol)
- Succinyl CoA (Porphyrin)
- Ribose- 5 Phosphat (Nucleotida)
 REGULASI METABOLISME

 Key-Enzym kecepatan proses

anabolisme dan katabolisme : kontrol
metabolisme yang efektif
 ENZYM : - mekanisme feedback
(Allosterik)
- modifikasi kovalent
- jumlah enzym
- kompartementasi enzym
 REGULASI METABOLISME

Kompartementasi enzym :
 Matrix mitochondria : Siklus Krebs,
Phosphorilasi oksidatif, -Oksidasi,
Synthese badan keton
 Cytosol : Glycolysis, Pentose Phosphat
Cycle, Synthese Fatty Acid
 Keduanya : Gluconeogenesis, Urea
Cycle
 REGULASI METABOLISME

 Glycolysis
: Fructose 6-phosphat
ATP ATP
Citrat Phosphofructokinase
AMP ADP
F2,6 BP Fructose 1,6-bisphosphat
 REGULASI METABOLISME

 Pentose Phosphat Cycle :

Glucose 6-phosphat
NADP+
G6Pdehydrogenase
NADPH
6-Phosphoglucono--lacton
 REGULASI METABOLISME

 Gluconeogenesis :
Fructose 1,6-bisphosphat
Citrat H2O
AMP Fructose 1,6-
F2,6 BP bisphosphatase
Pi
Fructose 6-phosphat
 Acetyl CoA

Oxaloacetate Citrate

Malate Isocitrate

CO2
Fumarate  Ketoglutarat

CO2

Succinate Succinyl Co A
 Enzym :
Citrate synthase
Aconitase
Isocitrate dehydrogenase 
-Ketoglutarate dehydrogenase 
Succinyl CoA synthetase
Succinate dehydrogenase +
Fumarase
Malate dehydrogenase 
 NAD + NADH + H+
+ FAD FADH2
 REGULASI METABOLISME

 TCA Cycle :
1. Citrat synthase
2. Isocitrat dehydrogenase
3. -Ketoglutarat dehydrogenase

ATP aktivitas enzim

 REGULASI METABOLISME

 Synthese Asam Lemak :

Acetyl- CoA
HCO3- + ATP
Citrat Acetyl-CoA-
Palmityl- CoA carboxylase

ADP + Pi
Malonyl - CoA
 REGULASI METABOLISME

 Metabolisme Glykogen :
 Polymer dari Glukosa (UDP-Glu)
 Synthase dan Phosphorilase yang
dikoordinir oleh hormon
 REGULASI METABOLISME

 Glucose 6-phosphat, berasal dari :

- mobilisasi glykogen
- pyruvat (melalui gluconeogenesis)
- asam amino glukogenik
 Pyruvat, berasal dari :
- glucose 6-phosphat
- katabolisme alanin
- lactat (melalui oksidasi di hepar)
 REGULASI METABOLISME

 Pyruvat :
- di mit. Pyruvat dikarboksilasi menjadi
Oxaloacetat
- di cyt. Oxaloacetat didekarboksilasi
phosphorilasi menjadi
Phosphoenolpyruvat
 Acetyl- CoA, berasal dari :
- pyruvat (melalui dekarboksilasi
oksidatif)
- proses -oksidasi asam lemak
- asam amino ketogenik
 REGULASI METABOLISME

Glucose

Glucose 6-phosphat

Glucose 1-P Fructose 6-P 6-Phosphogluconat

Glykogen Pyruvat Ribose 5-P

 REGULASI METABOLISME

Glucose 6-P Lactat

Pyruvat

Oksaloacetat Alanin
Acetyl- CoA
3 Hydroxy-3 methylglutaryl CoA FA
CO2
Cholesterol Badan Keton
 REGULASI METABOLISME

Pyruvate Amino acids Fatty acids

Acetyl- CoA

TCA Cycle Ketone bodies Sterols and

fatty acids
 REGULASI METABOLISME
Glucose
Glycolysis

Pyruvate

Transamination Carboxylation Oxidative Reduction

decarboxylation

Alanine Oxaloacetate Acetyl-CoA Lactate

 Metabolic effects of Insulin and Glucagon

 Communication between tissues :

 Nervous system
 Circulating substrates
 Levels of plasma hormones
 Integration of energy metabolism :
 Insulin, Glucagon, Catecholamines
 Insulin :
 polypeptide hormone
 coordinating the utilization of fuels by tissues
 metabolic effects are anabolic : synthesis of Glycogen,
Triacylglycerols and Protein
 Metabolic effects of Insulin

 Regulation of Insulin secretion

 Stimulation :
 Glucose
 Amino acids (elevated plasma Arginine)
 Gastrointestinal hormones
 Inhibition :
 When there is a scarcity of dietaryfuels and also
during periods of trauma
 These effects Epinephrine.
 Epinephrine can override the normal glucose-
stimulated release of Insulin
 Metabolic effects of Insulin

 Metabolic effects of Insulin :

 Effects on Carbohydrate metabolism :
 Liver, Muscle and Adipose tissues
 Liver : decreases the production of glucose by
inhibiting gluconeogenesis and the breakdown of
glycogen
 Muscle and Liver : increases glycogen synthesis
 Muscle and Adipose tissue : increases glucose uptake
by increasing the number of GLUT 4 on the cell
membrane
 Metabolic effects of Insulin

 GLUT 4 : insulin-sensitive glucose transport

protein.
 Some tissues have Insulin-independent
systems for glucose transport :
 Hepatocytes
 Erythrocytes
 Cells of the nervous system
 Intestinal mucosa
 Renal tubules
 Cornea
 Metabolic effects of Insulin

 Insulin-receptor complex internalized and

degraded in the lysosomes
 The receptors are recycled to the cell surface
 Elevated levels of Insulin promote the
degradation of receptors (down regulation)
 Insulin induced changes in enzymic activity
occur over minutes to hours
 Insulin initiates an increase in the amount of
many enzymes (Glukokinase, Pyruvate kinase
Phosphofructokinase), which requires hours to
days.
 Metabolic effects of Insulin

 Effects on Lipid metabolism :

 Adipose tissues responds within minutes to
administration of insulin marked reduction in
the release of fatty acids.
 Insulin decreases the level of circulating fatty acids
by inhibiting the activity of hormone-sensitive lipase
in adipose tissue decrease in TG degradation
 Insulin increases the transport and metabolism of
glucose into adipocytes and increases lipoprotein
lipase activity of adipose tissue increased TG
synthesis
 Metabolic effects of Insulin and Glucagon

 Effects on Protein synthesis :

 Insulin stimulates the entry of amino acids
into cells and protein synthesis.
 Metabolic effects of Glucagon :
 Glucagon, Epinephrine, Cortisol and GH
opposes many of the actions of Insulin
 Maintain blood glucose levels by activation of
hepatic glycogenolysis and gluconeogenesis.
 Glucagon secretion is increased by : low
blood glucose, amino acids and epinephrine.
 Metabolic effects of Glucagon

 Metabolic effects of Glucagon :

 Glucagon secretion is decreased by :
elevated blood sugar and by Insulin.
 Effects on carbohydrate metabolism :
immediate rise in blood sugar
 Effects on lipid metabolism : hepatic
oxidation of fatty acids and formation of
ketone bodies.
 Effects on protein metabolism : increases
uptake of amino acids by the liver
 Diskusi Regulasi Metabolisme

 Glucose Transporter (GLUT) :

 GLUT 1 : Brain, Kidney, Colon, Placenta and
Erythrocyte
 GLUT 2 : Liver, Pancreatic B cell, Small
intestine, Kidney
 GLUT 3 : Brain, Kidney, Placenta
 GLUT 4 : Heart and Skeletal Muscle, Adipose
tissue
 GLUT 5 : Small intestine
 SGLT 1 : Small intestine and Kidney.
 Diskusi Regulasi Metabolisme

 GLUCONEOGENESIS :
 Pyruvate carboxylase (mt):
 ATP, Biotin, CO2 , Mg++
 Pyruvate Oxaloacetate
 Phosphoenolpyruvate carboxykinase (cyt):
 GTP or ITP
 Glucose 6 Phosphatase :
 Present in liver and kidney
 Absent from muscle and adipose tissue
 Diskusi Regulasi Metabolisme

 Glycosuria :
 Reabsorption of glucose is linked to the
provision of ATP in the tubular cells
 Rearpsorption rate : 350 mg/min.
 Normal individual : glycosuria occurs when
the venous blood glucose concentration :
> 9,5 – 10 mmol/l termed as
Renal Treshold for glucose