METABOLISME KARBOHIDRAT

Dr. Dra. Trini Suryowati, MS

TUJUAN
• 1. Memahami metabolisme karbohidrat secara umum
• 2. Memahami jalur-jalur metabolisme karbohidrat serta peranannya
• 3. Memahami pengendalian metabolisme karbohidrat
• 4. Memahami beberapa penyakit yang terkait dengan kelainan
metabolisme karbohidrat
METABOLISME KARBOHIDRAT
GLUCOSA METABOLISM
Glycolysis
 GLIKOLISIS
glyco = gula, lysis = memecah

• Glikolisis -> reaksi tahap pertama secara aerob (cukup oksigen) berlangsung dalam mitokondria.
• Tahapan glikolisis tidak memerlukan oksigen dan tidak menghasilkan banyak energi.
• Tahap glikolisis merupakan awal terjadinya respirasi sel.

• Tahapan Glikolisis terjadi dalam sitoplasma , hasil akhir glikolisis : asam piruvat.
• Glikolisis dapat berlangsung secara aerob maupun anaerob,
• Glikolisis melibatkan enzim ATP dan ADP
• Peran ATP dan ADP pada glikolisis adalah mentransfer fosfat dari molekul yang satu ke molekul
yang lain.
• Pada sel eukariotik, glikolisis terjadi di sitoplasma (sitosol).
• Glikolisis terjadi melalui 10 tahapan yang terdiri dari 5 tahapan penggunaan energi dan 5
tahapan pelepasan energi .
 STEP IN GLYCOLISIS
• 1: Hexokinase
• 2 : Phosphoglucose Isomerase
• 3 : Phosphofructokinase
• 4 : Aldolase
• 5 : Triosephosphate isomerase
• 6 : Glyceraldehyde-3-phosphate Dehydrogenase
• 7 : Phosphoglycerate Kinase
• 8 : Phosphoglycerate Mutase
• 9 : Enolase
• 10 : Pyruvate Kinase

Steps 1 and 3 = – 2ATP

Steps 7 and 10 = + 4 ATP
Net “visible” ATP produced = 2.
 GLIKOLISIS
glyco = gula, lysis = memecah
• Glikolisis terdiri dari lima kategori yakni
• transfer fosforil
• pergeseran fosforil
• Isomerisasi
• dehidrasi
• pemecahan aldol.
VIOLATION OF GLYCOLISIS
 METABOLISME KARBOHIDRAT

• FUNGSI KARBOHIDRAT : SUMBER ENERGI ( GLUKOSA )

• MONOSAKARIDA : HEKSOSA
• HASIL PENCERNAAN KARBOHIDRAT TERUTAMA :
* GLUKOSA
* FRUKTOSA
* GALAKTOSA
• FRUKTOSA DAN GALAKTOSA DI HATI GLUKOSA
Metabolisme karbohidrat :

1. Glikolisis
2. Glikogenesis
3. Glikogenolisis
4. HMP Shunt
5. Glukoneogenesis
Kadar Glukosa darah : 80-180g/dl

Berlebih -> hiperglikemia -> radikal bebas

Kekurangan -> hipoglikemia
GLUKOSA -> GLIKOGEN
(HATI DAN OTOT)
Glycogenesis
Sintase and Branching Enzyme
Glycogenolysis pathway
Glycogenolysis
Glycogenesis and Glycogenolisis
Proses pemecahan glikogen

Dalam otot :
* mendapat energi bagi , hasil akhirnya : piruvat / laktat
karena glukosa 6-p yg dihasilkan dr glikogenolisis
masuk ke jalur glikolisis di otot

Dalam hati :
* mempertahankan kadar glukosa darah di antara dua waktu makan
* Glukosa 6-p akan diubah menjadi glukosa
Glukosa 6-p + H2O Glukosa + Pi
Glukosa 6-fosfatase
 GLUKONEOGENESIS
• Pembentukan glukosa dari bahan bukan karbohidrat
• Pada mmalia terutama terjadi di : hati dan ginjal
• Substrat :
1. Asam laktat dr. otot, eritrosit
2. Gliserol dr. hidrolisis Triasilgliserol dlm. jar.
lemak ( adiposa )
3. Asam amino glukogenik ruminansia
4. Asam propionat
• Glukoneogenesis -> penyediaan glukosa bila karbohidrat
tidak cukup dlm asupan
FUNCTION OF GLUCONEOGENESIS
• de novo glucose synthesis
• effectively glycolysis in reverse
• can maintain blood glucose when glycogen stores are exhausted
• must supply brain and RBCs which utilize glucose for energy
• is NOT a source of energy for the liver
• hepatocytes use β-oxidation to supply the energy needed for
gluconeogenesis
• potential substrates
FUNCTION OF GLUCONEOGENESIS

• potential substrates
• all amino acids
• except for leucine and lysine
• lactate
• produced in anaerobic glycolysis
• glycerol-3-phosphate
• produced in fat catabolism
• propionyl-CoA
• produced in odd-carbon fatty acid catabolism
PATHWAY OF GLUCONEOGENESIS

• location
• hepatocytes (primary)
• kidney
• enterocytes
• NOT muscle
• no glucose-6-phosphatase
• cannot release free glucose
Enzymes of Gluconeogenesis
• pyruvate carboxylase
• pyruvate → oxaloacetate
• requires biotin and ATP
• activated by acetyl-CoA
• oxaloacetate must be converted to malate to exit the mitochondria via the malate-aspartate
shuttle
• in mitochondria
• PEP carboxykinase (PEPCK)
• oxaloacetate → phosphoenolpyruvate (PEP)
• requires GTP
• activated by glucagon and cortisol
• in both cytosol and mitochondria
Enzymes of Gluconeogenesis
• fructose-1,6-bisphosphatase
• fructose-1,6-bisphosphate → fructose-6-P
• important control point of gluconeogenesis
• activated by ATP, inhibited by AMP and fructose-2,6-bisphosphate
• in cytosol
• glucose-6-phosphatase (G6P)
• glucose-6-P → glucose
• in ER of hepatocytes
• clinical relevance
• von Gierke disease = G6P deficiency
• see Glycogen metabolism
Other enzyme of Gluconeogenesis
• lactate dehydrogenase
• lactate → pyruvate
• requires free NAD+
REGULATION AND INHIBITION

• regulation
• stimulation
• glucagon
• acetyl CoA
• citrate
• inhibition
• high NADH/NAD+ ratio
• alcohol may cause elevated NADH/NAD+ ratio leading
to hypoglycemia
The Pentose Phosphate Pathway

The pentose
phosphate
pathway (PPP),

also known as
the hexose
monophosphate
(HMP) shunt,
REGULATION of PENTOSE PHOSPHATE PATHWAY
REFERENSI

• Murray R. K., et al., Ϯ01Ϯ. Harper’s Illustrated Biochemistry, 29th edition.

The McGraw-Hill Company.
• Marks A, et al., 2013. Marks’ Basic Medical Biochemistry : A Clinical Approach, 4th ed.
Lippincott Williams & Wilkins, a Wolters Kluwer business.
• American Diabetes Association, 2017. Standards of medical care in
diabetes 2017. Diabetes Care 2017;40 (Suppl. 1):S1–S131.
• Powers A.C., 2008. Harrison’s Principles of Internal Medicine, 17th edition. New York:
McGraw-Hill.
• Brownlee M., 2005. The Pathobiology of Diabetic Complications A Unifying
Mechanism. Diabetes. 54: 1615-1625.
KP METABOLISME KARBOHIDRAT 2