- Fructose metabolism occurs primarily in the liver, intestine and kidney. Fructose is converted to fructose-1-phosphate by fructokinase and can then enter the glycolysis or gluconeogenesis pathways. - Defects in fructose metabolism can cause disorders like essential fructosuria (deficiency of fructokinase) or hereditary fructose intolerance (deficiency of aldolase B). Patients with these defects need to restrict dietary fructose intake. - The polyol pathway converts glucose to fructose via sorbitol and is related to complications of diabetes like cataracts due to sorbitol accumulation inside cells. Inhibitors

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