CARBOHYDRATES METABOLISM

BY

Dr. WIDODO S., MKes

MEDICAL FACULTY BRAWIJAYA UNIVERSITY MALANG

INTRODUCTION
==> BIOCHEMISTRY IN OUR BODY :

ANABOLISM
CATABOLISM BIOENERGETIC

DIGESTION :
FOOD INTAKE ( CARBOHYDRATES )

DIGESTION

ENZYME : AMILASE, MALTASE, SACHARIDASE

MONOSACHARIDES : HEXOSE : glucose, maltose, fructose PENTOSE : ribose

DIGESTION : FOOD INTAKE : 40-45 % IS CARBOHYDRATE : * Amilopectin ( 60 % ) * Glucose * Fructose ==> fruit * Lactose ==> milk * Sucrose and Sacarose

ENZYMES : SALIVA AMILASE AND PANCREAS AMILASE, OLIGOSACHARIDASE, DISACHARIDASE intestine

GLUCOSE
IN THE LIVER ; ==> Glycogenesis ==> Glycogen ( storage )

==> pentosa pathway( HMP ) ==> Ribose, NADPH

==> Oxidation ==> ENERGY

==> Glukoronic Acid ==> detoxification IN MUSCLE : ==> Glycogenesis ==> Glycogen ==> Oxidation ==> ENERGY
IN ADIPOSE TISSUE : ==> TRIACYL GLYSEROL ( TG ) ==> STORAGE

 IN THE BRAIN : Oxidation ==> ENERGY -Ketoglutarate ==> detoxification of NH3 Neurotransmitter IN RED BLOOD CELL :
==> Oxidation ==> ENERGY ==> Bi-phosphoglycerate( BPG ) HbO2 Dissociations ==> HMP pathway( Pentosa ) ==> NADPH : GS-SG ==> 2G-SH ==> Scavenger ==>Hb H 2 O2 H 2 O + O2

IN THE KIDNEY : Glycogenesis

Glycogen

CARBOHYDRATE METABOLISM
1. GLYCOLISIS 2. PYRUVATE OXIDATION ACETYL- Co A 3. CYTRIC ACID CYCLE ( TCA CYCLE ) 4. GLUCONEOGENESIS 5. GLYCOGENESIS & GLYCOGENOLISIS 6. H M P SHUNT 7. URONIC ACID PATHWAY 8. FRUCTOSE METABOLISM 9. GALACTOSE METAB. & LACTOGENESIS 10. CARBOHYDRATE METAB. REGULATION 11. CH METAB DESEASE= DM

1. GLYCOLYSIS
ENZYMATIC REACTION FOR GLUCOSE OXIDATION AEROB : GLUCOSE PYRUVATE AN AEROB : GLUCOSE PYRUVATE LACTIC ACID PURPOSE : 1. PRODUCE ENERGY 2. SOURCE OF PYRUVATE CYTRIC ACID CYCLE ENERGY

OCCURRED IN CYTOPLASM ( EXTRA MYTOCONDRIA )

G L Y C O L Y S I S

Glycolysis is the cytosolic pathway of all mammalian cells for the metabolism of glucose ( or glycogen ) to pyruvate or lactate. Glycolysis can function anae3robically by regenerating oxidized NAD+ ( required in the glyceraldehyde-3phosphate dehydrogenase reaction ) by reducing pyruvate to lactate. Lactate is the end product of glycolysis under anaerobic conditions ( eq. in exercising muscle ) or when the metabolic machinery is absent for the further oxidation of pyruvate ( eq. In erythrocytes ). Glycolysis is regulated by three enymes catalyzing nonequilibrium reactions ( key enzyme ) : hexokimase, phosphofructokinase, and pyruvate kinase. Inerythrocytes, the first site in glycolysis for generation of ATP may be bypassed, leading to the formation of 2,3-bisphosphoglycerate, which is important in gecreasing the affinity of hemoglobin for O2.

AN AEROB CONDITION: PYRUVATE + NADH + H + LACTATE DEHYDROGENASE ENZYME ACTIVATION LACTATE + NAD +

ATP PRODUCTION FROM GLYCOLYSIS: AEROB: SUBTRATE LEVEL = 2 X 2 = 4 ATP RESPIRATION LEVEL = 2 X 3 = 6 ATP + = 10 ATP FOR ACIVATION NEED = 2 ATP ATP TOTAL= 8 ATP AN AEROB: SUBTRATE LEVEL = 2 X 2 = 4 ATP RESPIRATION LEVEL = .. = 0 ATP + = 4 ATP FOR ACTIVATION NEED = 2 ATP ATP TOTAL = 2 ATP

2. PYRUVATE OXIDATION TO ACETYL-CoA

CONNECTION BETWEEN GLYCOLISIS AND TCA CYCLE ENZYME : PYRUVATE DEHYDROGENASE COMPLEX
(MULTIENZYME COMPLEX IN THE MYTOCHONDRIA), THAT IS DEPENDENT ON THE VITAMIN COFACTOR THIAMIN DIPHOSPHATE )

PYRUVATE SHOULD BE TRANSPORTED INTO MYTOCHONDRIA

ATP PRODUCTION = 2 X 3 = 6 ATP. 1 MOL GLUCOSE METABOLIZE TO 2 MOL. PIRUVAT, 2 MOL. PYRUVATE 1 MOL. ACETYL Co A 2 ACETYL Co A 3 ATP

FIRST STEP OF THE REACTION : REACTION OF PYRUVATE WITH THIAMIN DIFOSFATE COENZYME

PYRUVATE

ACETYL- CoA :

3. CITRIC ACID CYCLE ( CAC ) = KREBS CYCLE = TRICARBOXYLIC ACID CYCLE ( TAC )
FUNCTION : 1. COMMON METABOLISM PATHWAY FOR OKSIDATION OF CARBOHYDRATE, FAT AND PROTEIN.
2. AMPHIBOLIC PATHWAY 3. KETO GLUTARAT ( KG) SOURCE - BRAIN : DETOXICIFICATION OF NH 3 - LIVER : ASPARTIC ACID FOR UREA CYCLE 4. PRODUCE ENERGY ( ATP )

ATP PRODUCTION DURING TCA CYCLE : 1. SUBTRAT E LEVEL .. 2. OXIDATION RESPIRATION : 3 MOL NADH + H+ ... 1 MOL FADH + H... TOTAL 1 MOL. GLUCOSE PRODUCE : GLYCOLISIS : PYRUVATE OXIDATION: TCA CYCLE : TOTAL

= 1 ATP = 9 ATP = 2 ATP + = 12 ATP

= = = =

8 ATP 6 ATP 24 ATP 38 ATP

4 . GLUCONEOGENESIS
SYNTHESIS OF CH (GLUCOSE) FROM OTHER NON-CARBOHYDRATES SOURCE (FATTY ACID; AMINO ACID; GLYCEROL ; Etc.) ENDOGEN GLUCOSE SOURCE FUNCTION: TO SUSTAIN GLUCOSE BLOOD LEVEL DURING GLUCOSE INTAKE IS LOW : STARVATION, STRESS Etc IMPORTANT ROLE OF GLUCOSE : 1. BRAIN ELIMINATION OF TOXIC NH 3 2. RED BLOOD CELL ENERGY & DPG SOURCE FOR HbO 2 DISSOCIATIONS IN MAMMALIA OCCURRED AT LIVER AND KIDNEY

Glukoneogenesis is the process of converting noncarbohydrates ( eq. amino acids, lactate, glycerol, and propionate ) to glucose or glycogen. The pathway of gluconeogenesis in the liver and kidney utilizes those reactions in glycolysis which are reversible plus four additional reactions that circumvent the irreversible nonequilibrium reactions. The liver regulates the blood glucose . Insulin is secreted as a direct response to hyperglycemia; it stimulates the liver to store glucose as glycogen and facilitates uptake of glucose into extrahepatic tissues.

Glucagon is secreted as a response to hypoglycamia and activates both glycogenolysis and gluconeogenesis in the liver, causing release of glucose into the blood.

5.

GLYCOGENESIS & GLYCOGENOLYSIS

GLYCOGENESIS : GLUCOSE GLYCOGEN GLICOGENOLYSIS : GLYCOGEN GLUCOSE GLYCOGENESIS PATHWAY : GLYCOGEN : CH SOURCE FOUND IN THE LIVER 5 6 % OF THE LIVER IS GLYCOGEN FOOD INTAKE CH, GLYCOGEN LIVER : 10 15 % GLYCOGEN STORAGE IN THE LIVER: RUN OUT AFTER 12 18 HOURS PASCA ABSORBTION GLYCOGEN IS ALSO FOUND IN MUSCLE, KIDNEY AND OHER TISSUE

Glycogen storage disease :

Glycogen represents the principal storage form of carbohy drate in the body, mainly in the liver and muscle.
In the liver, its major function is provide glucose for extrahepatic tissues. In muscle, it serves mainly as a ready source of metabolic fuel for use in muscle. Glycogen is synthesized from glucose by the pathway of glycogenesis. It is broken down by glycogenolysis pathway. Glycogenolysis leads to glucose formation in liver and lactate formation in muscle owing to the respective presence or absence of glucose-6-phosphatase. Inherited deficiencies in specific enzyme of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases.

7. HMP SHUNT = HEXOSE MONOPHOSPHATE

SHUNT = PENTOSE PHOSPHATE PATHWAY

FUNCTIONS:
1. NADPH SOURCE ( FOR REDUCTION REACTIONS) : + FATTY ACID SYNTHESIS + AMINO ACID SYNTHESIS + STEROID SYNTHESIS + PHOTOSYNTHESIS REACTION

2. RIBOSE SOURCE FOR NUCLEOTIDE (ATP, GTP ETC) AND NUCLEIC ACID (RNA, DNA) FOR PROTEIN SYNTHESIS 3. RIBULOSE SOURCE FOR CHLOROPLAST ORGANISM , FIXATION OF CO2.

HMP SHUNT present in the cytosol, can account for the complete oxidation of glucose, producing NADPH and CO2, but not ATP. The pathway has an oxidative phase, which is irreversible and generates NADPH; and non oxidative phase , which is reversible and provides Ribose precursors for nucleotide synthesis. The complete pathway is present only in those tissues having a requirement for NADPH for reductive synthesis, eq, lipogenesis or steroidogenesis, whereas the non oxidative phase is present in all cells requiring ribose. In erythrocytes, the pathway has a major function in preventing hemolysis by providing NADPH to mainting glutathione in the reduced state as the substrate for glutathione peroxidase.

8. URONIC ACID PATHWAY

THE URONIC ACID PATHWAY IS THE SOURCE OF GLUCORONIC ACID FOR CONJUGATION OF MANY ENDOGENOUS AND EXOGENOUS SUBSTANCES BEFORE EXCRETION AS GLUCORONIDES IN URINE

AND BILE.

9. THE METABOLISM OF FRUCTOSE :

FRUCTOSE BYPASSES THE MAIN REGULATORY STEP IN GLYCOLYSIS, CATALYZED BY PHOSPHOFROCTOKYNASE AND STIMULATES FATTY ACID SYNTHESIS AND HEPATIC TRIACYLGLYCEROL SECRETION.

CONVERTION GALACTOSE TO GLUCOSE

GALACTOSE IS SYNTHESIZED FROM GLUCOSE IN THE LACTATING MAMMARY GLAND AND IN OTHER TISSUES WHERE IS REQUIRED FOR THE SYNTHESIS OF GLYCOLIPIDS, PROTEOGLYCANS, AND GLYCOPROTEINS.

REFERENCES :
** PETER N. CAMPBELL; ANTHONY D.SMITH : BIOCHEMISTRY
ILLUSTRATED, 3rd ED., 1994 ** DAWN B.MARKS,PhD; ALLAN D. MARKS, MD; COLLEEN M.

SMITH, PhD : BASIC MEDICAL BIOCHEMISTRY A CLINICAL

APPROACH; WILLIAMS & WILKINS BALTIMORE; 1996 ** ROBERT K. MURRAY; DARYL K. GRANNER; PETER A. MAYES; VICTOR W. RODWELL : HARPERS BIOCHEMISTRY, 26th ED, INTERNATIONAL EDITION; 2003 ** PETER N. CAMPBELL; ANTHONY D.SMITH; TIMOTHY J. PETERS : BIOCHEMISTRY ILLUSTRATED BIOCHEMICAL AND MOLECULAR BIOLOGY; 4TH ED., 2005 ** STRYER LUBERT : BIOCHEMISTRY; 2ND ED., STANFORD UNIVER CITY NEW YORK.