FRUTOSE METABOLISMDR ROHINI C SANE

PROFESSOR

DEPARTMENT OF BIOCHEMISTRY

DR D Y PATIL MEDICAL COLLEGE

EBENE

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

FRUTOSE METABOLISM

IN ADIPOSE TISSUE & MUSCLE

FRUCTOSE

HEXOKINASE

FRUCTOSE 6 PHOSPHATE

GLYCOLITIC PATHWAY

FRUCTOSE METABOLISMFRUCTOSE

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

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

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

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)

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

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

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MAJOR DISORDERS OF FRUCTOSE METABOLISM• I ESSENTIAL FRUCTOSURIA DUE LACK OF FRUCTO KINASE .

• A LOW FRUCTOSE DIET IS RECOMMENDED.

II FRUCTOSE 1,6 BIPHOSPHATASE DEFICIENCY• PREVENTS GLUCONEOGENESIS

• BLOOD SUGAR LEVEL MAINTANANCE IS DEPENDANT ON EXOGENOUS GLUCOSE

• LACTIC ACIDOSIS

• HYPERVENTILATION

• HYPOGLYCEMIA

• KETOSIS

• COMA

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.

Hereditary fructose intolerance ---deficiency of Aldolase BEssential Fructosuria ----fructokinase

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• Thank you