kuliah 2 metabolisme kh
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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 dioxideAirChlorophyl
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
GlucoseGlucoseGlucose
The FullMonty
GlucoseGlycogenLactate
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 darahGlycogenolysisGluconeogenesisLactatePyruvateGlycerolAmino AcidsPropionatemengganti glucose dgn cara lemak dimetabolis.
Stage 3- Early starvationGluconeogenesis
Stage 4 – Intermediate starvationgluconeogenesisKetone 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
GlycogenEnergy 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 PyruvateLactate (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
Siklus Siklus 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
PropionatMeningkatkan glucose darahMerangsang pelepasan insulin
ButyratTidak digunakan utk synthesis glucoseMerangsang pelpasan insulinMerangsang pelepasan glucagon
Meningkatkan glucose darahAcetat
Tidak dipakai untuk synthesis glucoseTidak memacu pelepasan insulin
GlucoseEmacu 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
GlycogenEnergy 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
GlycogenEnergy 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
GlycogenEnergy 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
Glycogenesis
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
al l t imes regardless of state...
The relative rates of synthesis and
breakdown change
Synthesis and breakdown occur at
all t imes 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