kuliah 8 des

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KULIAH BIOKIMIA8 DESEMBER 2011

1. JELASKAN YANG DIMAKSUD

DENGAN SIKLUS CORI (CORI

CYCLE) ?

The Cori cycle (also known as Lacticacid cycle), named after its discoverers,Carl Cori and Gerty Cori, refers to the

metabolic pathway in which lactateproduced by anaerobic glycolysis in the

muscles moves to the liver and isconverted to glucose, which then returns

to the muscles and is converted back tolactate.

Gerty Cori withher husband andfellow-Nobelist,Carl Cori in 1947

The Cori cycle also operates more efficiently

when the muscular activity has stopped.At this time the oxygen debt can be made upso that the citric cycle and electron transport

chain also begin to function again.

In order for most of the lactic acid to beconverted to glucose, some must be

converted to pyruvic acid and then to acetylCoA.

The citric acid cycle and electron transportchain must provide ATP to "fuel" the

gluconeogenesis of the remainder of the lacticacid to glucose.

2. Jelaskan regulasi-regulasi dari

a. Glikogenesis

b. Glikogenolisis

GLYCOGEN

Glikogenesis

The α-1,6 branches in glucose are producedby amylo-(1,4–1,6)-transglycosylase, alsotermed the branching enzyme.This enzyme transfers a terminal fragment

of 6-7 glucose residues (from a polymer atleast 11 glucose residues long) to aninternal glucose residue at the C-6 hydroxylposition.

Glikogenesis

Action of branching enzyme

Regulation of Glycogen Synthesis(Glycogenesis)

Glycogen synthase is the key enzyme is glycogensynthesis.The activity of glycogen synthase is regulated byphosphorylation of serine residues in the subunitproteins. The effects of these phosphorylations leads to: 1. Decreased affinity of glycogen synthase for

UDP-glucose.

2. Decreased affinity of glycogen synthase forglucose-6-phosphate.

3. Increased affinity of glycogem synthase forATP and Pi.

Glycogenolysis

Degradation of stored glycogen occurs through theaction of glycogen phosphorylase.

Glycogen phosphorylase cannot remove glucoseresidues from the branch points (α-1,6 linkages) in

glycogen.The removal of branch point glucose residues requiresthe action of debranching enzyme, which contains 2activities: glucotransferase and glucosidase.

The transferase activity removes the terminal 3 glucose

residues of one branch and attaches them to a free C-4end of a second branch.

The glucose in α-(1,6)-linkage at the branch is thenremoved by the action of glucosidase.

Glycogenolysis

Debranching enzyme activity

Regulation of Glycogenolysis

Glycogen phosphorylase is an enzyme that existin two distinct conformational states: a T (fortense, less active) and R (for relaxed, moreactive) state.Glycogen Phosphorylase is capable of binding toglycogen when the enzyme is in the R state.This conformation is enhanced by binding of AMPand inhibited by binding ATP or glucose-6-

phosphate.

3. JELASKAN PERSAMAN DANPERBEDAAN PROSES HMP SHUNT DGGLIKOLISIS !!

4. JELASKAN TAHAPAN-TAHAPANREAKSI DLM HMP SHUNT !!

Kesamaan dengan glikolisis :

starting point : Glukosa 6P.Perbedaan dengan glikolisis :

◦Menggunakan NADP bukan NAD.◦Menghasilkan CO2, tidak dihasilkanpada glikolisis-anaerob

◦Tidak menghasilkan ATP.◦Menghasilkan Ribosa fosfat.

Pentose PhosphatePathway (HMP SHUNT)

Generation of NADPHand Pentoses

The pentose phosphate pathway is analternate route for the oxidation of glucose.

Overview

Function◦ NADPH production

Reducing powercarrier◦ Synthetic pathways

Role as cellularantioxidants

◦ Ribose synthesis Nucleic acids andnucleotides

Demand for NADPH

◦ Biosynthetic pathwaysFA synthesis (liver, adipose, mammary)

Cholesterol synthesis (liver)

Steroid hormone synthesis (adrenal,ovaries, testes)

◦ Detoxification (Cytochrome P-450System) – liver

◦ Reduced glutathione as an antioxidant(RBC)

◦ Generation of superoxide (neutrophils)

Characteristics:

Oxidative and Non-oxidative Phases Oxidative phases

◦ Reactions producingNADPH

◦ Irreversible Non-oxidative phases

◦ Produces ribose-5-P◦ Reversible reactions feed

to glycolysis

Oxidative phases

1. Dehydrogenation of glucose 6-phosphateto 6-phosphoglucono-lactone, catalyzedby the enzyme glucose-6-phosphatedehydrogenase.

2. The hydrolysis of 6-phospho-

gluconolactone, catalyzed by thegluconolactone hydrolase.

3. Decarboxylation of 6-phosphogluconateby 6-phosphogluconate dehydrogenase, which

requires NADP+ as hydrogen acceptor toform the ketopentose, ribulose 5-phosphate.

Reaction summaryGlucose 6-phosphate + 2 NADP++ H2O ribose 5-phosphate + CO2 + 2 NADPH + 2 H+

In this phase:ribulose 5-phosphate is converted backto glucose 6 phosphate by a series ofreactions as follows:

(a) Ribulose 5-phosphate 3-epimerase:alters the configuration aboutcarbon 3, forming another ketopentos

xylulose 5-phosphate.

2. Non-oxidative reversible phase

(b) Isomerase:

converts ribulose 5-phosphate to thecorresponding aldopentose, ribose 5phosphate, which is the precursor of

the ribose required for nucleotide andnucleic acid synthesis.

(c) Transketolase:

Catalyzes the transfer of the two-carbon unitfrom xylulose 5-phosphate toribose 5-phosphate, producing the 7- carbonketose sedoheptulose 7-phosphate and thealdose glyceraldehydes 3-phosphate. Thisreaction requires Mg2+ and thiaminpyrophosphate (TPP) as coenzyme.

(d) Transaldolase: Allows the transfer of carbons 1-3 from theketose sedoheptulose 7-phosphate onto the aldoseglyceraldehydes 3-phosphate to form the hexosefructose 6-phosphate and the four-carbon aldoseerythrose 4-phosphate. In a further reaction

catalyzed by transketolase, xylulose 5-phosphatedonates a two-carbon unit to erythrose 4-phosphate to form fructose 6-phosphate andglycerldehyde 3-phosphate.

Summary of Reaction

5. SEBUTKAN DAN JELASKANGANGGUAN LAIN AKIBATKELAINAN METABOLISMEKARBOHIDRAT

Glycogen Storage Diseases:

-- A family of serious,although not necessarily fatal,diseases caused by mutations

in the enzymes involving inglycogen storage andbreakdown.

Glikogenosis

Glikogenosis (Penyakit penimbunan glikogen)adalah sekumpulan penyakit keturunan yangdisebabkan oleh tidak adanya 1 atau beberapa

enzim yang diperlukan untuk mengubah gulamenjadi glikogen atau mengubah glikogenmenjadi glukosa (untuk digunakan sebagaienergi).Pada glikogenosis, sejenis atau sejumlah

glikogen yang Abnormal diendapkan di dalam jaringan tubuh, terutama di hati.

Fruktosuria

Fruktosuria merupakan suatu keadaan yangtidak berbahaya, dimana fruktosa dibuang kedalam air kemih.Fruktosuria disebabkan oleh kekurangan enzim

fruktokinase yang sifatnya diturunkan.1 dari 130.000 penduduk menderita fruktosuria.Fruktosuria tidak menimbulkan gejala, tetapikadar fruktosa yang tinggi di dalam darah dan

air kemih dapat menyebabkan kekeliruandiagnosis dengan diabetes mellitus.Tidak perlu dilakukan pengobatan khusus.

kuliah 8 des

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