CARBOHYDRATE METABOLISM

BIOMOLECULAR BIOCHEMISTRY FACULTY OF MEDICINE BRAWIJAYA UNIVERSITY

ATP

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

GLUCOSE METABOLISM
IN THE LIVER : >Oxidation ENERGY >Glycogenesis Glycogen ( storage ) >fatty acid TG VLDL >pentose pathway( HMP ) Ribose, NADPH >Glukonic Acid detoxification IN MUSCLE : >Oxidation ENERGY >Glycogenesis Glycogen IN ADIPOSE TISSUE : >TRIACYL GLYSEROL ( TG ) STORAGE

IN THE BRAIN : >Oxidation ENERGY >-Ketoglutarate NH3 detoxification >Neurotransmitter

IN THE KIDNEY :

>Glycogenesis Glycogen

IN RED BLOOD CELL : >Oxidation ENERGY >Bisphosphoglycerate( BPG ) HbO2 Dissociations >HMP pathway( Pentosa ) NADPH (Scavenger in RBC):

GS-SG ------- >2G-SH

H2O2 ------- >H2O + O2 (toxic)

CARBOHYDRATE METABOLISM IN GENERAL

LACTATE PYRUVATE ACETYL CoA
RESP. CHAIN

ATP

GLYCOGEN

ATP

TCA
NADH, FADH AA

TG
FRUCTOSE

GLUCOSE HMP PATHWAY RIBOSE NADPH URONIC PATHWAY GALACTOSE RNA DNA

LACTOSE

PROTEIN

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 METABOLISM DISEASE

1. GLYCOLISIS

OCCURRED IN CYTOPLASM ENZYMATIC REACTION FOR GLUCOSE OXIDATION AEROB : GLUCOSE PYRUVATE AN AEROB : GLUCOSE PYRUVATE LACTIC ACID PURPOSE : 1. PRODUCE ENERGY 2. SOURCE OF PYRUVATE ATP

anaerob

Lactate

ATP PRODUCTION FROM GLYCOLYSIS: AEROB: SUBTRATE LEVEL RESPIRATION LEVEL (NADH) FOR ACIVATION NEED ATP TOTAL = 2 X 2 = 2 X 3 = = = 4 ATP = 6 ATP + 10 ATP -2 ATP 8 ATP

AN AEROB:
NADH NAD PYRUVATE ------------------>LACTATE SUBTRATE LEVEL RESPIRATION LEVEL FOR ACTIVATION NEED ATP TOTAL = 2 X 2 = 0 X 3 = = = 4 ATP = 0 ATP 4 ATP - 2 ATP 2 ATP

2. PYRUVATE OXIDATION

PYRUVATE OXIDATION
- CONNECTION BETWEEN GLYCOLYSIS AND TCA CYCLE - ENZYME = PYRUVATE DEHYDROGENASE COMPLEX (ENZYME IN THE MYTOCHONDRIA) - PYRUVATE SHOULD BE TRANSPORTED IN TO MYTOCHONDRIA ATP PRODUCTION = 2 X 3 = 6 ATP. 1 MOL GLUCOSE METABOLIZE TO 2 PYRUVATE, 2 PYRUVATE 2 ACETYL Co A 1 MOL ACETYL Co A = 3 ATP - FIRST STEP OF THE REACTION : REACTION OF PYRUVATE WITH THIAMINE DIPHOSPHATE COENZYME

Pyruvate

Thiamine diphosphate

Thiamine diphosphate

Acetyl-CoA

NADH

3. CYTRIC ACID CYCLE

CYTRIC ACID CYCLE

FUNCTION : 1. COMMON METABOLISM PATHWAY FOR OXIDATION OF CARBOHYDRATE, FAT AND PROTEIN. 2. AMPHIBOLIC PATHWAY (CROSSROAD BETWEEN ANABOLIC AND CATABOLIC PATHWAY) 3. KETO GLUTARATE ( KG) SOURCE BRAIN : DETOXICIFICATION OF NH 3 LIVER : ASPARTIC ACID FOR UREA CYCLE 4. PRODUCE ATP

ACETYL Co A
KoA-SH H2O OXALOASETATE NADH + H+
Citrate synthase

CYTRATE
Akonitase

ISOCYTRATE NAD+
Isocytrate dehydrogenase

Malate dehydrogenase

NAD+ MALATE
Fumarase

NADH + H+ OXALOSUCCINATE

CAC

Isocytrate dehydrogenase

-KG

CO2
NAD+

H2O

KG dehydrogenase kompl
NADH + H+ SUCINNYL C-oA GDP
Succinate tiokinase

FUMARATE
FADH+H+
Succinate dehydrog.

FAD+
MYTOCHONDRIA

SUCCINATE

GTP

ATP PRODUCTION DURING TCA CYCLE :

1. SUBSTRATE LEVEL 2. OXIDATION RESPIRATION : 3 MOL NADH + H+ = 3 X 3 ATP 1 MOL FADH + H = 1 X 2 ATP TOTAL = 1 ATP = 9 ATP = 2 ATP + = 12 ATP

1 MOL GLUCOSE PRODUCE :

GLYCOLISIS : PYRUVATE OXIDATION: TCA CYCLE : TOTAL = 8 ATP = 6 ATP = 24 ATP + = 38 ATP

4 . GLUCONEOGENESIS

GLUCONEOGENESIS

OCCURRED IN LIVER AND KIDNEY SYNTHESIS OF CH (GLUCOSE) FROM OTHER CH SOURCE : FATTY ACID, AMINO ACID, GLYCEROL ENDOGEN GLUCOSE SOURCE FUNCTION: TO SUSTAIN GLUCOSE BLOOD LEVEL DURING GLUCOSE INTAKE IS LOW : STARVATION, STRESS

IMPORTANT ROLE OF GLUCOSE :

1. BRAIN ELIMINATION OF TOXIC NH 3 2. RED BLOOD CELL ENERGY & DPG SOURCE FOR HBO2 DISSOCIATIONS

Fatty acid

TO BE CONTINUED

5. GLYCOGENESIS & GLYCOGENOLISIS

GLYCOGENESIS & GLYCOGENOLISIS

GLYCOGENESIS GLYCOGENOLYSIS : GLUCOSE GLYCOGEN : GLYCOGEN GLUCOSE

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 OTHER TISSUE

GLYCOGEN

INSULIN
GLYCOGEN SYNTHASE GLYCOGEN PHOSPHORILASE

GLUCOSE 1-PHOSPHATE GLUCOSE 6-PHOSPHATE

GLUCOSE 6PHOSPHATASE GLUCOKINASE

GLUCOSE

6. HMP SHUNT

HMP SHUNT
FUNCTIONS: 1. NADPH SOURCE ( FOR REDUCTION REACTIONS) : + ANTIOXIDANT PROCESS + 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.

ANTIOXIDANT PROCESS

toxic

NADPH NADPH

SYNTHESIS OF NUCLEOTIDES, DNA AND RNA

Glucose 6-Phosphate

Glucose 6-Phosphate

Glucose 6-Phosphate

7. URONIC ACID PATHWAY

7. URONIC ACID PATHWAY

- URIDINE DIPHOSPHATE GLUCORONATE, SOURCE FOR : GLUCORONIDES

PROTEOGLICANS (collagen, connective tissue)

- ASCORBATE/ VIT. C SYNTHESIS (IN OTHER THAN PRIMATES AND GUINEA PIGS)

URONIC ACID PATHWAY

(Block in primate And guinea pigs)

8. FRUCTOSE METABOLISM

FRUCTOSE METABOLISM

SOURCE OF FRUCTOSE : - FOOD (EXOGEN SOURCE) - HEKSOSE / MONOSACHARIDE IN THE LIVER CHANGE TO FRUCTOSE (ENDOGEN) THIS PATHWAY IS IMPORTANT FOR DIABETIC PATIENT TO OBTAIN ENERGY, SINCE GLYCOLYSIS PATHWAY IS ATTENUATED IN THIS PATIENT. BUT IF GLUCOSE CONCENTRATION IS HIGH SORBITOL INCREASE (POLLI-OL/ALKOHOL =TOXIC) MEMBRANE CELL DAMAGE, REACT WITH RETINAL COLLAGEN RETINO ANGIOPATHY LENS KATARAK LENTIS DEF. FRUKTOKINASE ESSENSIAL FRUCTOSURIA DEF. ENZ.ALDOLASE B FRUCTOSE INTOLERANCE

FRUCTOSE METABOLISM

SORBITOL

D-fructose

DIET

FATTY ACID ESTERIFICATION

FATTY ACID SYNTHESIS

9. GALACTOSE METABOLISM & LACTOGENESIS

GALACTOSE METABOLISM & LACTOGENESIS

IN HEPAR:
GALACTOSE GLUCOSE
LACTOGENESIS

PHYSIOLOGIC FUNCTION : - LACTOSE ( BREAST FEEDING ) - GLYCOLIPID - PROTEOGLYCAN - GLYCOPROTEIN.

ENZYME IN GALACTOSE METABOLISM : - GALACTOKINASE - GALACTOSE 1 PURIDIN TRANSFERASE - URIDIN DIPHOSPHOGALACTOSE 4 EPIMERASE

GALACTOSE METABOLISM

Glicolipid, proteoglycan, glycoprotein

LACTOGENESIS

10. CARBOHYDRATE METABOLISM DISEASE

CH METABOLISM DYSFUNCTION
LACTOSA INTOLERANCE DIABETES MELLITUS ( DM ) GLICOGENOSIS

PENTOSURIA
FRUCTOSURIA ESSENTIAL HEREDITER FRUCTOSA INTOLERANS GALACTOSEMIA

LACTOSE INTOLERANCE
OFTEN IN BABY CAUSE : LACTASE INSUFISIENSY LACTOSE IS NOT DYGEST LACTOSE IN INTESTINE
OSM. INTESTIN. LUMEN
WATER IN INTESTINE LUMEN FERMENTATION LACTOSE BY INTESTIN. BACTERIAL GAS 2 : CO2, CH4 IRITANT

DIARHEA

FLATULENCE

VOMITE

DIABETES MELLITUS COMPLICATION

DIABETES MELLITUS ( DM )
TYPE I = INSULIN DEPENDENT DM (IDDM) INSULIN SHOULD BE GIVEN, SINCE PANCREAS DOES NOT PRODUCE INSULIN OCCURRED SINCE BABY JUVENILE D.M TIPE II = NON INS. DEPENDENT DM (NIDDM) 90% OF DM PATIENT

DIABETES MELLITUS
ROLE OF INSULIN :
1.
2. 3. 4. 5.

6.

Induce glycolysis key enzyme Inhibit gluconeogenesis key enzyme induce HMP shunt enzyme increase Glut4 Activate phosphodiesterase, Glycogen sinthetase inhibit phosphorilase

1. 2. 3. 4.
5. 6.

CONSEQUENCE IN DM: GLYCOLYSIS GLUCONEOGENESIS HMP SHUNT Glukosa DIFFICULT to enter cell Glycogenesis Glycogenolysis

HYPERGLYCEMIA

D.M PATIENT BECAUSE OF INSULIN DEF: 1. DYSFUNCTION OF CH METAB. 2. DYSFUNCTION OF LIPID METAB. 3. DYSFUNCTION OF PROTEIN METAB.

1. DYSFUNTION OF CH METABOLISM IN DM
GLYCOGEN SYNTHETASE IS NOT ACTIVE >>, PHOSPHORYLASE ENZYME TURN ACTIVE

DECREASE GLYCOGENESIS ; INCREASE GLYCOGENOLYSIS DECREASE GLYCOLYSIS; INCREASE GLUCONEOGENESIS

ADIPOSE TISSUE:

INH IBITION OF GLUCOSE MOBILIZATION IN TO SEL GLYCOLYSIS DECREASE; HMP SHUNT DECREASE

DECREASE LIPOGENESIS ( TG FORMATION )

BLOOD SUGAR >N

HYPERGLYCEMIA HYPERGLYCEMIA

GLUCOSURIA

INSULIN
ADENYLATE SICLASE ATP (+) PHOSPHATASE GLYCOGEN SINTHETASE ( INACTIVE ) cAMP

(+)

PHOSPHO DIESTERASE 5-AMP

PROTEIN KINASE ( INACTIVE )

PROTEIN KINASE ( ACTIVE ) GLYCOGEN SINTHETASE ( ACTIVE ) GLYCOGEN PHOSPHORILASE A GLUCOSE-1P PHOSPHORILASE B

PHOSPHORILASE KINASE ( ACTIVE )

PHOSPHATASE

GLUCOSE

GLUCOSE-6P

1. DYSFUNTION OF CH METABOLISM IN DM
GLYCOGEN SYNTHETASE IS NOT ACTIVE >>, PHOSPHORYLASE ENZYME TURN ACTIVE

DECREASE GLYCOGENESIS ; INCREASE GLYCOGENOLYSIS DECREASE GLYCOLYSIS; INCREASE GLUCONEOGENESIS

ADIPOSE TISSUE:

INH IBITION OF GLUCOSE MOBILIZATION IN TO SEL GLYCOLYSIS DECREASE; HMP SHUNT DECREASE

DECREASE LIPOGENESIS ( TG FORMATION )

BLOOD SUGAR >N

HYPERGLYCEMIA HYPERGLYCEMIA

GLUCOSURIA

GLUCOSE IN URINE INCREASE URINE OSMOLALITY INCREASE URINE VOLUME OSMOTIC DIURESIS DEHYDRATION DEHYDRATIN CONDITION: DM PATIENT ALWAYS THIRSTY

POLIURI

POLIDIPSI

GLUCOSE IN URINE WASTE OF ENERGY STIMULATION OF CENTRAL APETITE DM PATIENT NEED MORE FOOD

POLIFAGIA CHRONIC HYPERGLYCEMIA GLYCOSILATION

COLAGEN GLYCOSILATION BLOOD VESSEL ENDOTEL

ATHEROSCLEROSIS

2. LIPID METABOLISM DYSFUNCTION

INSULIN DEFFICIENCY DECREASE LIPOGENESIS, INCREASE LIPOLISIS DECREASE BODY WEIGHT DECREASE BODY WEIGHT INCREASE FFA MOBILIZATION STIMULATE FFA OXIDATION IN LIVER INCREASE ACETYL CoA
KETOGENESIS KETON BODIES (ACETONE, ACETO ACETATE, HYDROXI BUTIRATE)
KETOACIDOSIS KETONEMIA COMA DIABET

INCREASE KOLESTEROL SYNTHESIS

GLYCOSILATION OF BLOOD VESSEL ENDOTEL

HYPERCHOLESTEROLEMIA

ATHEROSCLEROSIS

3. PROTEIN METABOLISM DYSFUNCTION

INSULIN DEFICIENCY

TRANSMEMBRAN AA TRANSPORTER DECREASE AA MOBILIZATION IN TO CELL PROTEIN SYNTHESIS

DECREASE DECREASE DECREASE DECREASE

TRANSCRIPTION TRANSLATION REPLICATION CELL PROLIF.

INHIBITION OF TISSUE REGENERATION WOUND HEALING impairment

GLUCOSE METABOLISM IN NORMAL CONDITION

VESSEL BRAIN
RED BLOOD CELL

KIDNEY

LIVER

G
PANCREAS
INSULIN

TG

GLUCOSE GLYCOGEN G

G
GLYCOGEN

Glucose

G
INTESTINE

IF

MUSCLE

GLUCOSE METABOLISM IN DIABETIC PATIENT

KIDNEY VESSEL
G> 180 mg/dl

LIVER
CHOLESTEROL

VLDL
FFA GLYS

VLDL TG

GLUCOSURIA

ACETYL Co A KETON BODIES

KB
G G
GLISERAL DEHID 3P FFA

GLYCOGEN

ADIPOSE G
GLIYCOGEN PYRUVATE

AA
G INTESTINE PROTEIN

MUSCLE

STARVATION
NO / DECREASE GLUCOSE INTAKE ALL GLUCOSE METABOLIZE BY THE TISSUE BLOOD GLUCOSE CONCENTRATION DECREASE

PANCREAS : INHIBITION OF INSULIN SECRETION INCREASE OF GLUKAGON SECRETION

GLYCOGENOLYSIS LOW INSULIN GLUCOSE INCREASE GLUCOSE INTO CELL

GLUCONEOGENESIS MUSCLE ENERGY SOURCE DERIVED FROM ADIPOSE FFA MOBILIZATION (INCREASE LIPOLYSIS)

THANK YOU