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CARBOHYDRATE METABOLISM. Atip Likidlilid. METABOLISM. Living organisms maintain complex order in dynamic steady state by importing food and energy from their surroundings. transformation of matter and energy to create complex molecules from simple ones by enzyme-catalyzed reactions .

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CARBOHYDRATE

METABOLISM

Atip Likidlilid


METABOLISM

  • Living organisms maintain complex order in dynamic steady state by importing food and energy from their surroundings.

  • transformation of matter and energy to create complex molecules from simple ones by enzyme-catalyzed reactions


METABOLIC PATHWAYS

  • series of consecutive enzymatic reactions that produce specific products

  • products of reactions

metabolites

End products

(metabolic intermediates)


Principal characteristics of metabolic pathways


1.Metabolic pathways are irreversible

  • highly exergonic

  • reactions go to completion


A

1

2

Y

X

If cells require metabolite

2

1

2

turn on

Independent control

2

1

turn off


2. Every metabolic pathway has a first committed step

  • irreversible ( exergonic ) reaction commits

    the intermediates down the pathway


3. All metabolic pathways are regulated

  • the first committed step is too slow to permit its substrate and product to equilibrate

  • most of other reactions in a pathway function close to equilibrium

  • committed step = rate-limiting step


4. Metabolic pathways in eukaryotic cells occur in specific cellular locations

  • biological membranes are selectively permeable to metabolites

  • specific transport protein


Metabolic reaction mechanisms

1. group-transfer reactions

2. oxidations and reductions

3. eliminations , isomerization and rearrangements

4. reactions that make or break C-C bonds


Metabolic categories

  • catabolism ( degradation )

  • anabolism ( biosynthesis)


complex metabolites

2-

ADP + HPO

4

+

NADP

degradation

biosynthesis

NADPH

ATP

simple products


CATABOLISM

1. digestion and absorption


starchsucroselactosecellulose

salivary amylase

starch starch dextrin + glucose + maltose


HCl stops action of amylase


Pancreatic amylase

starch dextrins

+ maltose

+ isomaltose


mucosal cells(brush border)

maltase , lactase , invertase , isomaltase , dextrinase

glucose , fructose , galactose

Portal circulation

liver

cellulose


galactose , frutose

from portal circulation

glucose

Glucose in systemic circulation

peripheral tissue


Transport of monosaccherides into tissues

  • 1. Na+ - dependent glucose transport

    Phlorhizin (plant glycoside) - inhibitor

  • 2. Facilitated glucose transport

    Cytochalasin (from mold) – inhibitor

    (GLUT5)


Transporter

Tissue distribution

1. Sodium-dependent unidirectional transporter

SGLT

1

(ใช้พลังงาน)

small intestine,kidney

2. Facilitated bidirectional transporters

GLUT1

red cells,blood brain barrier,kidney,colon

GLUT2

liver,pancreatic B-cells,small intestine

GLUT3

neuron,placenta,testes

GLUT4

fat,skeletal muscle,heart

(ใช้ insulin)

GLUT5

small intestine,testes

(fructose uptake)


Glycolysis (Pasteur effect)

  • anaerobic glycolysis (oxygen debt)

    glucose lactate

  • aerobic glycolysis (oxygen load)

    glucose pyruvate


Pathway of glycolysis (cytosol)

Stage 1 : formation of glucose 6 - P


hexose (fructose,galactose)

hexokinase

glucose

hexose 6-

P

glycogen

ATP

phosphorylase

hexokinase

Pi

isomerase

ADP

glucose 1-

glucose 6-

P

P

phosphoglucomutase

glycolysis


Stage 2 : split G-6- P 2 Triose- P


G-6- P

Phosphohexose isomerase

Fructose-6- P

ATP

*

Phosphofructokinase-1

ADP

Fructose-1,6-bis P

Aldolase

Dihydroxyacetone phosphate (DHAP) (95%)

Glyceraldehyde-

3- P

Triose- P -isomerase


Stage 3:Glyceraldehyde-3- P Pyruvate


Gly-3- P

Pi + NAD

+

Gly-3- P dehydrogenase

NADH+H

+

1,3-bis P - glycerate

aerobic O2

via cytochrome

ADP

Phosphoglycerate kinase

*

ATP

3- P - glycerate

Phosphoglycerate mutase

2- P - glycerate

Enolase

H2O


2- P - enolpyruvate

ADP

Pyruvate kinase

*

ATP

(couple reaction)

2- enolpyruvate

Pyruvate kinase

pyruvate

NADH+H+

Lactate dehydrogenase

NAD+

lactate

(anaerobic)

* substrate level phosphorylation


Energetics of glycolysis

ATP/mole of glucose

glycolysis

anaerobic

aerobic

1. hexokinase

-1

-1

2. phosphofructokinase-1

-1

-1

3. phosphoglycerate kinase

+2

+2

4. pyruvate kinase

+2

+2

-

+4 (+6)

5. 2 (NADH.H+ NAD+)

total

+2

+6(+8)


Inhibitors in glycolysis


1. glyceraldehyde-3- P dehydrogenase

  • 1.1 Iodoacetate (ICH2COO-)

    • SH group of cysteine residue in active site of the enzyme by covalent bond

  • 1.2 Arsenate (AsO43-) (uncoupler)

    • competitve inhibitor of Pi

    • uncouple oxidation and phosphorylation

      2. enolase: required Mg2+ for activity

    • Fluoride (F-) forms tightly bound complex with Mg2+ at the active site


Regulation of glycolysis

  • 3 allosteric enzymes

  • catalyzed non equilibrium reactions


Enzymes

Inhibitors

Activators

-

HK

G-6- P

PFK-1*

ATP,citrate,PEP

ADP,AMP, cAMP (by insulin), FBP (F-2,6- P ) F-6- P , NH4+, Pi

( rate limiting enzyme )

PK

ATP , alanine ,

fatty acid,acetyl CoA

FBP


Oxidation of pyruvate to acetyl Co A

  • pyruvate transporter (mitochondria)

  • pyruvate dehydrogenase complex

    • pyruvate dehydrogenase ( E1) ( TPP )

    • dihydrolipoamide acetyltransferase

      ( E2 ) ( lipoic acid )

    • dihydrolipoamide reductase

      ( E3 ) ( FAD , NAD )


TPP

pyruvate + NAD+ + Co A

Acetyl Co A + NADH.H+ + CO2


Regulation of pyruvate dehydrogenase complex

1. Control by product inhibitor

- NADH , acetyl Co A และ ATP

2. Comtrol by product activator

- pyruvate, ADP, Ca2+


Inhibitors of PDH complex

  • arsenite ( AsO2- ) and Hg2+ (mercuric ion )

    complex -SH of E2

  • lactic acidosis

  • neurologic disturbances


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