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Metabolisme Karbohidrat
Metabolisme:
proses-proses kimia yang terjadi di dalam
cell yang menghasilkan energy dan bahan
dasar penting yang dibutuhkan untuk
proses hidup.
- miliaran cell
- berbagai organs (liver, adipose, jantung, brain)
- ribuan enzyme
- berbagai kondisi (sesudah makan, puasa, exercise,
stress)
Photosynthesis: energy sinar matahari menjadi bagian dari
molekul glucose
energy
Carbon dioxide
Air
Chlorophyl
GLUCOSE
6 CO2 + 6 H20 + energy (sun) C6H12O6 + 6 O2
120 gram glucose / hari = 480 calori
Nasib Glucose
 Pada kondisi tidak berpuasa
 Glukosa disimpan sebagai glycogen
 di hati (Liver)
 di Otot rangka
 Glukosa disimpan sebagai lipida
 di Jaringan Adipose
 Pada kondisi berpuasa
 Glukosa dimetabolis untuk energy
 Synthesis glukosa baru
No mitochondria
Glucose
Glucose
Glucose
The Full
Monty
Glucose
Glycogen
Lactate
Nasib Glucose yang diserap
 1st
Priority: simpanan glycogen
 Disimpan dalam otot dan liver
 2nd
Priority: menyediakan energy
 Dioksidasi menjadi ATP
 3rd
Priority: disimpan sebagai lemak
 Hanya ketika glucose berlebihan
 Disimpan sebagai triglycerides di adipose
Stage 1 – setelah makan
All tissues utilize glucose
Stage 2 – post absorptive
KEY – memelihara glucose darah
Glycogenolysis
Gluconeogenesis
Lactate
Pyruvate
Glycerol
Amino Acids
Propionate
mengganti glucose dgn cara
lemak dimetabolis.
Stage 3- Early starvation
Gluconeogenesis
Stage 4 – Intermediate
starvation
gluconeogenesis
Ketone bodies
Stage 5 – Starvation
Metabolisme Carbohidrat /
Pemanfaatannya- di jaringan specific
 Jaringan Otot – Jantung dan rangka
 Oxidize glucose/produce and store glycogen (fed)
 Breakdown glycogen (fasted state)
 Shift to other fuels in fasting state (fatty acids)
 Adipose dan liver
 Glucose  acetyl CoA
 Glucose to glycerol for triglyceride synthesis
 Liver releases glucose for other tissues
 Nervous system (sistem syaraf)
 Always use glucose except during extreme fasts
 Reproductive tract/mammary
 Glucose dibutuhkan oleh fetus
 Lactose  karbohidrat utama pada susu.
 Cell darah merah
 No mitochondria
 Oxidize glucose to lactate
 Lactate returned to liver for Gluconeogenesis
Glucose darah tinggi
Glucose absorbed
Insulin
Pancreas
Otot
Adipose
Cells
Glycogen
Glucose absorbed
Glucose absorbed
Beberapa saat setelah makan
Pemanfaatan Glucose
Glucose
PyruvateRibose-5-phosphate
Glycogen
Energy
Stores
Pentose Phosphate
Pathway
Glycolysis
Adipose
• Saat glucose darah tinggi, metabolisme karbohidrat
terdiri atas:
1. Glycolisis
2. Glycogenesis
3. HMP Shunt
4. Oxidasi Pyruvat
5. Siklus Kreb’s
6. Diubah menjadi lemak
• Saat berpuasa (Fasting), metabolisme glukosa
darah terdiri atas:
1. Glycogenolisis
2. Gluconeogenesis
Glycolysis
 Serangkaian reaksi yang mengubah
glucose menjadi pyruvat
 Relatif sedikit jumlah energy yang dihasilkan
 reaksi Glycolysis terjadi di cytoplasma
 tidak membutuhkan oxygen
Glucose → 2 Pyruvate
Lactate (anaerobic)
Acetyl-CoA (TCA cycle)
CORY CYCLE
Siklus Krebs (TCA Cycle)
 Pada kondisi aerob TCA cycle menghubungkan
pyruvat ke phosphorylasi oxidatif
 Terjadi di mitochondria
 menghasilkan 90% energy yg diperoleh dari
bahn pakan, termasuk metabolism KH, protein,
dan lemak.
 acetyl-CoA teroksidasi menjadi CO2 dan energy
potential ditangkap sebagai NADH (or FADH2)
dan beberapa mol ATP
SiklusSiklus Krebs (Citric Acid Cycle)Krebs (Citric Acid Cycle)
Jumlah ATP per mol Glukose
Dari setiap mol glucose yang memasuki glycolysis,
diperoleh:
1. dari glycolysis: 2 ATP dan 2 NADH
2. dari tahap persiapan TCA (pyruvat ke acetyl-CoA): 2 NADH
3. dari siklus TCA (TCA) : 2 ATP, 6 NADH, dan 2 FADH2
TOTAL: 4 ATP + 10 NADH + 2 FADH2
CATATAN:
1 NADH setara dgn 3 ATP
1 FADH setara dgn 2 ATP
Asam lemak Volatil (VFA)
 Dihasilkan oleh bacteri pd fermentasi as. pyruvat
 Tiga asam lemak Volatil utama:
 Acetat

Sumber Energy dan untuk sintesis asam lemak
 Propionat

Dipakai untuk membentuk glucose via
gluconeogenesis
 Butyrat

Sumber Energy dan untuk sintesis asam lemak
Pemakaian VFA untuk Energy
 Memasuki siklus TCA teroxidasi
 Asam Acetat

menghasilkan 10 ATP
 Asam Propionat

menghasilkan 18 ATP
 Asam Butirat

menghasilkan 27 ATP

Sedikit asam butyrat yang masuk ke darah
Pemanfaatan VFA pd
Metabolisme
 Acetat
 Energy
 Sumber Carbon untuk asam lemak
 Adipose
 Mammary gland
 tidak dipakai untuk synthesis glucose
 Propionat
 Energy
 sumber utama untuk synthesis glucose
Butyrat
 Energy
 sumber carbon untuk asam lemak- di ambing
Pengaruh VFA terhadap sistem
Endocrin
Propionat
Meningkatkan glucose darah
Merangsang pelepasan insulin
Butyrat
Tidak digunakan utk synthesis glucose
Merangsang pelpasan insulin
Merangsang pelepasan glucagon
Meningkatkan glucose darah
Acetat
Tidak dipakai untuk synthesis glucose
Tidak memacu pelepasan insulin
Glucose
Emacu pelepasan insulin
Need More Energy (More ATP)??
 Working animals
 Horses, dogs, dairy cattle, hummingbirds!
 Increase carbon to oxidize
 Increased gut size relative to body size
 Increased feed intake
 Increased digestive enzyme production
 Increased ability to process nutrients
 Increased liver size and blood flow to liver
 Increased ability to excrete waste products
 Increased kidney size, glomerular filtration rate
 Increased ability to deliver oxygen to tissues and get rid of carbon
dioxide
 Lung size and efficiency increases
 Heart size increases and cardiac output increases
 Increase capillary density
 Increased ability to oxidize small carbon chains
 Increased numbers of mitochondria in cells
 Locate mitochondria closer to cell walls (oxygen is lipid-soluble)
Hummingbirds
 Lung oxygen diffusing ability 8.5 times
greater than mammals of similar body size
 Heart is 2 times larger than predicted for body
size
 Cardiac output is 5 times the body mass per
minute
 Capillary density up to 6 times greater than
expected
Rate of ATP Production
(Fastest to Slowest)
 Substrate-level phosphorylation
 Phosphocreatine + ADP Creatine + ATP
 Anaerobic glycolysis
 Glucose Pyruvate Lactate
 Aerobic carbohydrate metabolism
 Glucose Pyruvate CO2 and H2O
 Aerobic lipid metabolism
 Fatty Acid Acetate CO2 and H2O
Potential Amount of Energy
Produced
(Capacity for ATP Production)
 Aerobic lipid metabolism
 Fatty Acid Acetate CO2 and H2O
 Aerobic carbohydrate metabolism
 Glucose Pyruvate CO2 and H2O
 Anaerobic glycolysis
 Glucose Pyruvate Lactate
 Substrate-level phosphorylation
 Phosphocreatine + ADP Creatine + ATP
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
Adipose
Pentose Phosphate Pathway
 Secondary metabolism of glucose
 Produces NADPH

Similar to NADH

Required for fatty acid synthesis
 Generates essential pentoses

Ribose

Used for synthesis of nucleic acids
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
Adipose
Energy Storage
 Energy from excess carbohydrates
(glucose) stored as lipids in adipose tissue
 Acetyl-CoA (from TCA cycle) shunted to
fatty acid synthesis in times of energy
excess
 Determined by ATP:ADP ratios

High ATP, acetyl-CoA goes to fatty acid synthesis

Low ATP, acetyl CoA enters TCA cycle to generate
MORE ATP
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
Adipose
Glycogenesis
 Liver
 7–10% of wet weight
 Use glycogen to export glucose to the
bloodstream when blood sugar is low
 Glycogen stores are depleted after
approximately 24 hrs of fasting (in humans)
 De novo synthesis of glucose for glycogen
Glycogenesi
s
Glycogenesis
 Skeletal muscle
 1% of wet weight
 More muscle than liver, therefore more
glycogen in muscle, overall
 Use glycogen (i.e., glucose) for energy
only (no export of glucose to blood)
 Use already-made glucose for synthesis of
glycogen
Fates of Glucose
 Fed state
 Storage as glycogen
 Liver
 Skeletal muscle
 Storage as lipids
 Adipose tissue
 Fasted state
 Metabolized for energy
 New glucose synthesized
Synthesis and
breakdown occur at
all times
regardless of state...
The relative rates of
synthesis and
breakdown change
Synthesis and
breakdown occur at
all times
regardless of state...
The relative rates of
synthesis and
breakdown change
Fasting Situation in Non-Ruminants
 Where does required glucose come
from?
Glycogenolysis
Lipolysis
Proteolysis
 Breakdown or mobilization of glycogen stored by glucagon
 Glucagon - hormone secreted by pancreas during times of fasting
 Mobilization of fat stores stimulated by glucagon and epinephrine
 Triglyceride = glycerol + 3 free fatty acids
 Glycerol can be used as a glucose precursor
 The breakdown of muscle protein with release of amino acids
 Alanine can be used as a glucose precursor
Low Blood Glucose
Proteins Broken Down
Insulin
Pancreas
Muscle
Adipose
Cells
Glycogen
Glycerol, fatty acids released
Glucose released
In a fasted state, substrates for glucose
synthesis (gluconeogenesis) are released from
“storage”…
Gluconeogenesis
 Necessary process
 Glucose is an important fuel

Central nervous system

Red blood cells
 Not simply a reversal of glycolysis
 Insulin and glucagon are primary
regulators
Gluconeogenesis
 Vital for certain animals
 Ruminant species and other pre-gastric
fermenters

Convert carbohydrate to VFA in rumen
 Little glucose absorbed from small intestine
 VFA can not fuel CNS and RBC
 Feline species

Diet consists primarily of fat and protein

Little to no glucose absorbed
 Glucose conservation and gluconeogenesis
are vital to survival
Gluconeogenesis
 Synthesis of glucose from non-carbohydrate
precursors during fasting in monogastrics
 Glycerol
 Amino acids
 Lactate
 Pyruvate
 Propionate
There is no glucose synthesis from fatty acids
Supply carbon skeleton
Carbohydrate Comparison
 Primary energy substrate
 Primary substrate for fat synthesis
 Extent of glucose absorption from gut
 MOST monogastrics = glucose
 Ruminant/pre-gastric fermenters = VFA
 MOST monogastrics = glucose
 Ruminant = acetate
 MOST monogastrics = extensive
 Ruminant = little to none
Carbohydrate Comparison
 Cellular demand for glucose
 Importance of gluconeogenesis
 Nonruminant = high
 Ruminant = high
 MOST monogastrics = less important
 Ruminant = very important

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Kuliah 2 metabolisme kh

  • 2. Metabolisme: proses-proses kimia yang terjadi di dalam cell yang menghasilkan energy dan bahan dasar penting yang dibutuhkan untuk proses hidup. - miliaran cell - berbagai organs (liver, adipose, jantung, brain) - ribuan enzyme - berbagai kondisi (sesudah makan, puasa, exercise, stress)
  • 3. Photosynthesis: energy sinar matahari menjadi bagian dari molekul glucose energy Carbon dioxide Air Chlorophyl GLUCOSE 6 CO2 + 6 H20 + energy (sun) C6H12O6 + 6 O2
  • 4. 120 gram glucose / hari = 480 calori
  • 5. Nasib Glucose  Pada kondisi tidak berpuasa  Glukosa disimpan sebagai glycogen  di hati (Liver)  di Otot rangka  Glukosa disimpan sebagai lipida  di Jaringan Adipose  Pada kondisi berpuasa  Glukosa dimetabolis untuk energy  Synthesis glukosa baru
  • 7. Nasib Glucose yang diserap  1st Priority: simpanan glycogen  Disimpan dalam otot dan liver  2nd Priority: menyediakan energy  Dioksidasi menjadi ATP  3rd Priority: disimpan sebagai lemak  Hanya ketika glucose berlebihan  Disimpan sebagai triglycerides di adipose
  • 8. Stage 1 – setelah makan All tissues utilize glucose Stage 2 – post absorptive KEY – memelihara glucose darah Glycogenolysis Gluconeogenesis Lactate Pyruvate Glycerol Amino Acids Propionate mengganti glucose dgn cara lemak dimetabolis. Stage 3- Early starvation Gluconeogenesis Stage 4 – Intermediate starvation gluconeogenesis Ketone bodies Stage 5 – Starvation
  • 9. Metabolisme Carbohidrat / Pemanfaatannya- di jaringan specific  Jaringan Otot – Jantung dan rangka  Oxidize glucose/produce and store glycogen (fed)  Breakdown glycogen (fasted state)  Shift to other fuels in fasting state (fatty acids)  Adipose dan liver  Glucose  acetyl CoA  Glucose to glycerol for triglyceride synthesis  Liver releases glucose for other tissues  Nervous system (sistem syaraf)  Always use glucose except during extreme fasts  Reproductive tract/mammary  Glucose dibutuhkan oleh fetus  Lactose  karbohidrat utama pada susu.  Cell darah merah  No mitochondria  Oxidize glucose to lactate  Lactate returned to liver for Gluconeogenesis
  • 10. Glucose darah tinggi Glucose absorbed Insulin Pancreas Otot Adipose Cells Glycogen Glucose absorbed Glucose absorbed Beberapa saat setelah makan
  • 12. • Saat glucose darah tinggi, metabolisme karbohidrat terdiri atas: 1. Glycolisis 2. Glycogenesis 3. HMP Shunt 4. Oxidasi Pyruvat 5. Siklus Kreb’s 6. Diubah menjadi lemak • Saat berpuasa (Fasting), metabolisme glukosa darah terdiri atas: 1. Glycogenolisis 2. Gluconeogenesis
  • 13. Glycolysis  Serangkaian reaksi yang mengubah glucose menjadi pyruvat  Relatif sedikit jumlah energy yang dihasilkan  reaksi Glycolysis terjadi di cytoplasma  tidak membutuhkan oxygen Glucose → 2 Pyruvate Lactate (anaerobic) Acetyl-CoA (TCA cycle)
  • 14.
  • 15.
  • 17. Siklus Krebs (TCA Cycle)  Pada kondisi aerob TCA cycle menghubungkan pyruvat ke phosphorylasi oxidatif  Terjadi di mitochondria  menghasilkan 90% energy yg diperoleh dari bahn pakan, termasuk metabolism KH, protein, dan lemak.  acetyl-CoA teroksidasi menjadi CO2 dan energy potential ditangkap sebagai NADH (or FADH2) dan beberapa mol ATP
  • 18. SiklusSiklus Krebs (Citric Acid Cycle)Krebs (Citric Acid Cycle)
  • 19. Jumlah ATP per mol Glukose Dari setiap mol glucose yang memasuki glycolysis, diperoleh: 1. dari glycolysis: 2 ATP dan 2 NADH 2. dari tahap persiapan TCA (pyruvat ke acetyl-CoA): 2 NADH 3. dari siklus TCA (TCA) : 2 ATP, 6 NADH, dan 2 FADH2 TOTAL: 4 ATP + 10 NADH + 2 FADH2 CATATAN: 1 NADH setara dgn 3 ATP 1 FADH setara dgn 2 ATP
  • 20.
  • 21. Asam lemak Volatil (VFA)  Dihasilkan oleh bacteri pd fermentasi as. pyruvat  Tiga asam lemak Volatil utama:  Acetat  Sumber Energy dan untuk sintesis asam lemak  Propionat  Dipakai untuk membentuk glucose via gluconeogenesis  Butyrat  Sumber Energy dan untuk sintesis asam lemak
  • 22. Pemakaian VFA untuk Energy  Memasuki siklus TCA teroxidasi  Asam Acetat  menghasilkan 10 ATP  Asam Propionat  menghasilkan 18 ATP  Asam Butirat  menghasilkan 27 ATP  Sedikit asam butyrat yang masuk ke darah
  • 23. Pemanfaatan VFA pd Metabolisme  Acetat  Energy  Sumber Carbon untuk asam lemak  Adipose  Mammary gland  tidak dipakai untuk synthesis glucose  Propionat  Energy  sumber utama untuk synthesis glucose Butyrat  Energy  sumber carbon untuk asam lemak- di ambing
  • 24. Pengaruh VFA terhadap sistem Endocrin Propionat Meningkatkan glucose darah Merangsang pelepasan insulin Butyrat Tidak digunakan utk synthesis glucose Merangsang pelpasan insulin Merangsang pelepasan glucagon Meningkatkan glucose darah Acetat Tidak dipakai untuk synthesis glucose Tidak memacu pelepasan insulin Glucose Emacu pelepasan insulin
  • 25. Need More Energy (More ATP)??  Working animals  Horses, dogs, dairy cattle, hummingbirds!  Increase carbon to oxidize  Increased gut size relative to body size  Increased feed intake  Increased digestive enzyme production  Increased ability to process nutrients  Increased liver size and blood flow to liver  Increased ability to excrete waste products  Increased kidney size, glomerular filtration rate  Increased ability to deliver oxygen to tissues and get rid of carbon dioxide  Lung size and efficiency increases  Heart size increases and cardiac output increases  Increase capillary density  Increased ability to oxidize small carbon chains  Increased numbers of mitochondria in cells  Locate mitochondria closer to cell walls (oxygen is lipid-soluble)
  • 26. Hummingbirds  Lung oxygen diffusing ability 8.5 times greater than mammals of similar body size  Heart is 2 times larger than predicted for body size  Cardiac output is 5 times the body mass per minute  Capillary density up to 6 times greater than expected
  • 27. Rate of ATP Production (Fastest to Slowest)  Substrate-level phosphorylation  Phosphocreatine + ADP Creatine + ATP  Anaerobic glycolysis  Glucose Pyruvate Lactate  Aerobic carbohydrate metabolism  Glucose Pyruvate CO2 and H2O  Aerobic lipid metabolism  Fatty Acid Acetate CO2 and H2O
  • 28. Potential Amount of Energy Produced (Capacity for ATP Production)  Aerobic lipid metabolism  Fatty Acid Acetate CO2 and H2O  Aerobic carbohydrate metabolism  Glucose Pyruvate CO2 and H2O  Anaerobic glycolysis  Glucose Pyruvate Lactate  Substrate-level phosphorylation  Phosphocreatine + ADP Creatine + ATP
  • 30. Pentose Phosphate Pathway  Secondary metabolism of glucose  Produces NADPH  Similar to NADH  Required for fatty acid synthesis  Generates essential pentoses  Ribose  Used for synthesis of nucleic acids
  • 32. Energy Storage  Energy from excess carbohydrates (glucose) stored as lipids in adipose tissue  Acetyl-CoA (from TCA cycle) shunted to fatty acid synthesis in times of energy excess  Determined by ATP:ADP ratios  High ATP, acetyl-CoA goes to fatty acid synthesis  Low ATP, acetyl CoA enters TCA cycle to generate MORE ATP
  • 34.  Liver  7–10% of wet weight  Use glycogen to export glucose to the bloodstream when blood sugar is low  Glycogen stores are depleted after approximately 24 hrs of fasting (in humans)  De novo synthesis of glucose for glycogen Glycogenesi s
  • 35. Glycogenesis  Skeletal muscle  1% of wet weight  More muscle than liver, therefore more glycogen in muscle, overall  Use glycogen (i.e., glucose) for energy only (no export of glucose to blood)  Use already-made glucose for synthesis of glycogen
  • 36. Fates of Glucose  Fed state  Storage as glycogen  Liver  Skeletal muscle  Storage as lipids  Adipose tissue  Fasted state  Metabolized for energy  New glucose synthesized Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change Synthesis and breakdown occur at all times regardless of state... The relative rates of synthesis and breakdown change
  • 37. Fasting Situation in Non-Ruminants  Where does required glucose come from? Glycogenolysis Lipolysis Proteolysis  Breakdown or mobilization of glycogen stored by glucagon  Glucagon - hormone secreted by pancreas during times of fasting  Mobilization of fat stores stimulated by glucagon and epinephrine  Triglyceride = glycerol + 3 free fatty acids  Glycerol can be used as a glucose precursor  The breakdown of muscle protein with release of amino acids  Alanine can be used as a glucose precursor
  • 38. Low Blood Glucose Proteins Broken Down Insulin Pancreas Muscle Adipose Cells Glycogen Glycerol, fatty acids released Glucose released In a fasted state, substrates for glucose synthesis (gluconeogenesis) are released from “storage”…
  • 39. Gluconeogenesis  Necessary process  Glucose is an important fuel  Central nervous system  Red blood cells  Not simply a reversal of glycolysis  Insulin and glucagon are primary regulators
  • 40. Gluconeogenesis  Vital for certain animals  Ruminant species and other pre-gastric fermenters  Convert carbohydrate to VFA in rumen  Little glucose absorbed from small intestine  VFA can not fuel CNS and RBC  Feline species  Diet consists primarily of fat and protein  Little to no glucose absorbed  Glucose conservation and gluconeogenesis are vital to survival
  • 41. Gluconeogenesis  Synthesis of glucose from non-carbohydrate precursors during fasting in monogastrics  Glycerol  Amino acids  Lactate  Pyruvate  Propionate There is no glucose synthesis from fatty acids Supply carbon skeleton
  • 42. Carbohydrate Comparison  Primary energy substrate  Primary substrate for fat synthesis  Extent of glucose absorption from gut  MOST monogastrics = glucose  Ruminant/pre-gastric fermenters = VFA  MOST monogastrics = glucose  Ruminant = acetate  MOST monogastrics = extensive  Ruminant = little to none
  • 43. Carbohydrate Comparison  Cellular demand for glucose  Importance of gluconeogenesis  Nonruminant = high  Ruminant = high  MOST monogastrics = less important  Ruminant = very important

Notas del editor

  1. Lactate transported back to liver for glucose production “Cori Cycle”. Costs energy