kuliah 2 metabolisme kh

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 NADH2. dari tahap persiapan TCA (pyruvat ke acetyl-CoA): 2 NADH3. 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 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