Glukosa diperoleh dari asupan makanan.disimpan sebagai glikogen,setelah glokuneogenesis ,glukosa di ubah dari glikogen dalam hati atau otot untuk glikolisis.Glikolisis adalah pemecahan 6c glukosa kepada 2 3piruvat.

Fungsi liver dalam metabolism

Glukosa yang memasuki hepatosit diposporilasi oleh glikogenase menjadi glukosa-6-posfat.Monosakarida yang lain juga diubah menjadi G-6-P melalui glukoneogenesis,lalu glukosa disimpan dalam bentuk glikogen.Ketika kita membutuhkan energy,glukolisis mengubah G-6-P menjadi piruvat dan asetil CoA untuk memasuki siklus asam sitrat untuk memproduksi ATP melalui posforilasi oksidatif (metabolism aerobic)

Carbohydrate Metabolism Overview glycogen

pentose GLUCOSE other sugars pyruvate

acetyl CoA EtOHlactate

TCA cycle ATP

GLYCOLYSIS Glucose ATP hexokinase ADP Glucose 6-phosphate phosphogluco- isomerase Fructose 6-phosphate ATPphosphofructokinase ADP Fructose 1.6-bisphosphate aldolase

triose phosphate isomerase Dihydroxyacetone Glyceraldehyde phosphate 3-phosphate Glyceraldehyde 3-phosphateglyceraldehyde NAD+ + Pi

3-phosphate NADH + H+

dehydrogenase 1,3-Bisphosphoglycerate  ADPphosphoglycerate kinase ATP 3-Phosphoglyceratephosphoglyceromutase 2-Phosphoglycerate enolase H2O Phosphoenolpyruvate ADP pyruvate kinase ATP Pyruvate

glucoseÚ 6 CO2 = -2840 kJ/mole

2 ATPs produced = 2 x 30.5 =

61 kJ/mole glucose

Energy yield = 61/2840 = 2%

recovered as ATP

- subsequent oxidation of pyruvate and

NADH can recover more of the free

energy from glucose

3 reakasi kinase bolak balik :

Hexokinase atau glukoginase Phosfofrucktokinase Piruvat kinase

2 jalur anaeorbik :

Menjadi laktat melalui laktat dehidrogenase Menjadi ethanol melalui etanol dehidrogenase

Catatan : keduanya memakai NADH jadi hanya 2ATP per glukosa yang dibutuhkan

Summary of Energy Relationships

for Glycolysis aerobic Input = 2 ATP 1. glucose + ATP glucose-6-P 2. fructose-6-P + ATP fructose 1,6 bisphosphateOutput = 4 ATP + 2 NADH1. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+ 2 (1,3 bisphosphoglycerate) + 2 NADH2. 2 (1,3 bisphosphoglycerate) + 2 ADP 2 (3-P-glycerate) + 2 ATP3. 2 PEP + 2 ADP 2 pyruvate + 2 ATPNet = 2 ATP and 2 NADH( 8 ATP)

FERMENTASI LAKTAT

Enzym = laktat deehidrogenase

COO- COO-

C=O + NADH + H+ D H-C-OH + NAD+

CH3 CH3

pyruvate lactate

membantu mengemudikan glikolisis menggunakan NADH.Reversibel jadi piruvat dapat dibangun kembali dalam alternative metabolism.Fermentasi laktat penting dalam sel darah merah , bagian dari retina , dan di sel otot rangka pada saat kita melakukan olahraga.

Laktat dehidrogenase memiliki bermcam bentuk.sebuah isozyme.2 polipeptida “M” dan “H” dating bersamaan menuju dan dari LDH.

Hati menggunakan kebanyak an laktat ini untuk membuat glikogen.Hanya dalam jumlah kecil glukosa bebas dilepaskan.

FERMENTASI ALKOHOL

- pathway is active in yeast.- second step helps drive glycolysis - second step is reversible- reverse is ethanol oxidation,- eventially yields acetate, which- ultimately goes into fat synthesis.- ethanol Ò acetaldehyde Ò acetate - humans have alcohol dehydrogenase - in liver which mainly disposes of- ethanol.- acetaldehyde is reactive and toxic.

Alcoholic Fermentation

COO- CO2

CH2OH H O

C=O C + NADH CH3 +

CH3 CH3

NAD+

 pyruvate

acetaldehyde ethanol

pyruvate decarboxylase- irreversible

alcohol dehydrogenase- reversible

Note: NADH used up

REGULASI GLIKOLISIS

1.Hexokinase dan Glikokinase

Hexokinase

Langkah dalam glikolisis : fosporilase dari glukosa.Dihambat oleh produknya,G-6-P,sebagai respon untuk memperlambat glikolisis.Ditemukan dalam seluruh sel dari organisme rendah spesifisitinya untuk monosakarida. relative tinggi untuk gaya tarik glukosa KM=0,1mM

Glukokinase

Enzyme hati dengan Km yang tinggi (10 mM) untuk glukosa jadi paling efektif ketika tingkat glukosa sangat tinggi.Tidak dihambat oleh G-6-P.Sensitif kepada glukosa yang tinggi dalam sirkulasi dari beberapa makanan,jadi ini dapat meningkatkan tingkat glukosa dalam darah melali membawa glukosa ke dalam hati.

2.Posfofructokinase

rate limiting for glycolysis an allosteric multimeric regulator enzyme.Measures adequacy of energy levels.

u Inhibitors: ATP and citrate

high energy

u Activators: ADP, AMP, and

fructose 2,6 bisphosphate

low energy

ATP inhibits phosphofructose activity by decreasing fructose 6-phosphate bindingAMP and ADP reverse ATP inhibition

Fructose 2,6 bisphosphate is a very important regulator, controlling the relative flux of carbon through glycolysis versus gluconeogenesis.It also couples these pathways to hormonal regulation.

3.Piruvat Kinase

PEP + ADPÚ Pyruvate + ATP

SummaryGlucoseof Reactions 2 ATP 2 NADH 2 pyruvate2 NADH 2 NADHanaerobic anaerobic 2 ethanol + CO2 2 lactate 2 acetyl CoA + 2 CO2

  O2 aerobic 4 CO2 + 4 H2O

An allosteric tetramer

- inhibitor: ATP & acetyl CoA & fatty acids (alternative fuels for TCA cycle)

- activator: fructose 1,6-bisphosphate

- (“feed-forward”)

u Phosphorylation (inactive form) and dephosphorylation (active form) under hormone control. Also highly regulated at the level of gene expression(“carbohydrate loading”)

The rate of Glycolysis will influent the affinity oxygen and Hemoglobine,with the intermediate 2,3 BPG pathway.Disorder in glycolysis will influent the affinity hemoglobine and oxygen.Defficiency Piruvat kinase, so the level of 2.3 BPG will increase.The affinity of oxygen and hemoglobine loose, and hypoxia in the tissue .Anemia hemolytic.

Defisiensi heksokinase

-penyakit genetic

-2,3 BPG in RBC low

-Affinity Hb and Oxygen is very strong (abnormal)

-hypoxia jaringan

Defesiensi piruvat kinase (Anemia hemolitik)

Blockade The end of glycolytic pathway, The affinity of oxygen and Hb decrease. turun.- The production of ATP is not enough, so it decrease the activity of Na+ & K+, stimulate ion ATP ase pump. It will keep the membran cell of RBC. Defficiency Piruvate Kinase will make RBC Lysis.

Glikogenolisis

Glycogen degradation Occurs in cytosol Signal that glucose is needed is given by hormones

o epinephrine stimulates glycogen breakdown in muscleo glucagon which stimulates glycogen breakdown in liver in response to low BGo used to sustain blood glucose level between meals and to provide energy during an

emergency/exercise

Pentose Phosphate Pathway=Hexose Monophosphat Shunt

Generation of NADPH and Pentoses

Has 2 functions

1.Generate reducing equivalents NADPH (reduced cosubstrate/ coenzyme) needed for fatty acid synthesis, folate reduction

2. Produce ribose 5-phosphate needed for DNA and RNA synthesis

Occurs in cytosol of cells particularly important in anabolic tissues,liver, adrenal cortex, mammary glands and fat tissues muscle cells do NOT have HMS enzymes

Glucose-6-phosphate

6-Phospho- glucono-lactone

6-Phospho- gluconate

D-Ribulose-5-phosphateRNA or

DNA

Function

NADPH production

-Reducing power carrier

# Synthetic pathways

-Role as cellular antioxidants

Ribose synthesis

-Nucleic acids and nucleotides

Karakteristik : distribusi jaringan

Demand for NADPH

Biosynthetic pathways

FA synthesis (liver, adipose, mammary)

Cholesterol synthesis (liver)

Steroid hormone synthesis (adrenal, ovaries, testes)

Detoxification (Cytochrome P-450 System) – liver

Reduced glutathione as an antioxidant (RBC)

Generation of superoxide (neutrophils)