1. FRUTOSE METABOLISM
DR ROHINI C SANE
PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
DR D Y PATIL MEDICAL COLLEGE
EBENE

2. FRUCTOSE METABOLISM
• Dietary Source ---cane sugar,(equimolar concentration of fructose & glucose )
• Free form ---honey &fruits
• Entry of fructose not controlled by insulin(contrast to glucose regulated for its
entry into majority of tissues
• Metabolic site---liver, intestine, kidney
• Fructose +fructo kinase ---- fructose 1 phosphate
• monosaccharrides + hexokinase •fructose 6 phosphate
• hexokinase • low affinity (high km ) for fructose ----minor pathway
• fructose 1 phosphate+ ALDOSE B-C
• fructose 6 phosphate---FRUCTOSE 1,6 BIPHOSPHATE + ALDOSE A-
•  fructose 1 phosphate+ ALDOSE B

3. FRUTOSE METABOLISM
IN ADIPOSE TISSUE & MUSCLE
FRUCTOSE
HEXOKINASE
FRUCTOSE 6 PHOSPHATE
GLYCOLITIC PATHWAY

4. FRUCTOSE METABOLISM
FRUCTOSE
FRUCTOKINASE
FRUCTOSE 1 PHOSPHATE
ALDOLASE B
DIHYDROXY ACETONE PHOSPHATE + GLYCERALEDEHYDE
TRIOKINASE
GLYCERALEDEHYDE 3 PHOSPHATE
FRUCTOSE 1,6 BIPHOSPHATE
FRUCTOSE 6 PHOSPHATE
ALDOSE REDUCATASE
GLUCOSE 6 PHOSPHATE GLUCOSE SORBITOL
GLYCOGEN
NADPH +H NADP

5. FRUCTOSE METABOLISM
• GLYCERALDEHYDE +TRIOKINASE - GLYCERALDEHYDE -3 PHOSPHATE
• GLYCERALDEHYDE -3 PHOSPHATE--GLYCOLYSIS OR
GLUCONEOGENESIS
• LIVER -- METABOLISM OF FRUCTOSE MORE RAPID THAN GLUCOSE
(AS RETE LIMITING STEP REACTIONS OF GLYCOLYSIS CATALYSED BY
PHOSPHOFRUCTOKINASE BYPASSED )
• INCREASED DIETARY INTAKE OF FRUCTOSE –ELEVATES PRODUCTION
OF ACETYL COA & LIPOGENESIS(FATTY ACIDS ,TRIACYLGLEROL,VERY
LOW DENSITY LIPOPROTEIN SYNTHESIS)
• INGESTION OF LARGE QUANTITIES OF FRUCTOSE OR SUCROSE ---
HEALTH COMPLICATIONS

6. SORBITOL PATHWAY/POLYOL PATHWAY
• SORBITOL– POLYHYDROXY SUGAR
• SORBITOL PATHWAY/POLYOL PATHWAY CONVERSION OF GLUCOSE TO
FRUCTOSE VIA SORBITOL
• ABSENT IN LIVER
• DIRECTLY RELATED WITH GLUCTOSE CONCENTRATION
• HIGHER IN UNCONTROLLED DIEBETIS MELLITUS
• GLUCOSE +NADPH +ALDOSE REDUCTASE  SORBITOL(GLUCITOL)
• SORBITOL+NAD+SORBITOL DEHYDROGENASE FRUCOSE
• SORBITOL DEHYDROGENASE—LENSE &RETINA OF EYE ,KIDNEY ,PLACENTA
,SCHWAN CELLS OF PERIPHERAL NERVES ,ERYTHROCYTES ,SEMINAL VESCICLES
,SPLEEN ,OVARIES
• FULLFILLS ENERGY NEEDS OF SPERM CELLS

7. SORBITOL PATHWAY (POLYOL PATHWAY)
• OCCURS IN LENSE
• GLUCOSE CONVERTED IN SORBITOL & FRUCTOSE
• DIABETIS MELLITUS CONCENTRATION OF GLUCOSE INCREASES
CONCENTRATION OF SORBITOL& FRUCTOSE INCREASES
• GLUCOSE +ALDOSE REDUCTASE +NADPH+H+SORBITOL+NADP+
• SORBITOL +SORBITOL DEHYDROGENASE +NAD+FRUCTOSE +NADH+ H +
• PATHOGENESIS OF DIABETIS MELLITUS –CATARACT (LENSE OPAQUE)

8. SORBITOL PATHWAY/POLYOL PATHWAY—DIABETIS MELLITUS
• HYPERGLYCEMIA - INTRACELLULAR GLUCOSE (LENSE ,RETINA ,KIDNEY ,NERVE
CELLS ----HIGH ACTIVITIES OF ALDOSE REDUCTASE &NADPH )
• THEREFORE RAPID EFFICIENT CONVERSION OF GLUCOSE TO SORBITOL
• LOW ACIVITIES OF /ABSENCE OF SORBITOL DEHYDROGENASE ---SORBITOL NOT
CONVERTED TO FRUCTOSE
• SORBITOL GETS ACCUMULATED IN CELL AT SITE OF PRODUCTION
• SORBITOL HYDROPHILLIC NATURE –CAUSES STRONG OSSMOTIC EFFECTS
LEADING TO SWELLING OF CELLS ‘
• PATHOLOGICAL CHANGES IN DIEBETIS MELLITUS –CATARACT
FORMATION,PERIPHERAL NEUROPATHY ,NEPHROPATHY DUE TO ACCUMULATION
OF SORBITOL (PATHOGENESIS CAUSES DAMAGE TO TISSUE BECAUSE OF POLYOL
PATHWAY)
• FUTURE TREATMENT –OF DM RETINOPATHY –INHIBITORS OF SORBITOL
REDUCTASE

9. DEFECTS OF FRUCTOSE METABOLISM ESSENTIAL FRUCTOSURIA
• ESSENTIAL FRUCTOSURIA –DEFICIENCY OF FRUCTOKINASE
• FRUCTOSE --------FRUCTOSE 1PHOSPHATE
ASYMPTOMATICS –EXCRETION OF FRUCTOSE IN URINE
• TREATMENT----RESTRICTION OF DIETARY FRUCTOSE
• Hereditary fructose intolerance ---deficiency of Aldolase B
• Essential Fructosuria ----fructokinase
•

10. MAJOR DISORDERS OF FRUCTOSE METABOLISM
• I ESSENTIAL FRUCTOSURIA DUE LACK OF FRUCTO KINASE .
• A LOW FRUCTOSE DIET IS RECOMMENDED.

11. II FRUCTOSE 1,6 BIPHOSPHATASE DEFICIENCY
• PREVENTS GLUCONEOGENESIS
• BLOOD SUGAR LEVEL MAINTANANCE IS DEPENDANT ON
EXOGENOUS GLUCOSE
• LACTIC ACIDOSIS
• HYPERVENTILATION
• HYPOGLYCEMIA
• KETOSIS
• COMA

12. III HEREDIATARY FRUCTOSE INTOLERANCE
• AUTOSOMAL RECESSIVE DISORDER DUE TO DEFICIENCY OF FRUCTOSE
1 PHOSPHATE ALDOLASE (ALDOLASE B)
ENZYME BLOCK CAUSES
• ACCUMULATION OF FRUCTOSE 1 PHOSPHATE IN TISSUE
• LIVER DAMAGE & JAUNDICE DUE TO FRUCTOSE 1 PHOSPHATE IN
TISSUE—THAT CAN PROGRESS IN CIRRHOSIS &ASCITES
• RENAL TUBULAR DAMAGE
• HYPOGLYCEMIA DUE TO INHIBITION OF GLYCOGENOLYSIS
• LOW FRUCTOSE DIET RECOMMENDED.

13. Hereditary fructose intolerance ---deficiency of Aldolase B
Essential Fructosuria ----fructokinase

14. •
• Thank you