Carbohydrate metabolism

The phosphorylation of fructose 6-phosphate to fructose 1,6- bisphosphate is unique in glycolysis • Pyruvate kinase reaction 10 – ATP allosterically inhibits pyruvate kinase to slow gly

Lecture 3 (3 hours)

Metabolism of other important

carbohydrates: fructose, galactose

and mannose

Instructor: Dr Nguyen Thao Trang

School of Biotechnology Semester I 2015-2016

ADVANCED BIOCHEMISTRY

Overview of glycolysis

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Biochemistry by Cambell and Farrell

•  Includes 10 reactions divided into 2 stages:

Stage 1 (Preparation step): reactions 1-5

-  Glucose is phosphorylated, then converted to fructose which is

again phosphorylated and cleaved into 2 molecules of glyceraldehyde-3-phosphate

- In this stage, 2 ATP molecules are used

Stage 2 (Harvesting ATP): reactions 6-10

-  Two molecules of glyceraldehyde-3-phosphate are converted

to 2 pyruvate molecules

-  In this stage, 4 ATP and 2 NADH molecules are produced

ATP production = ATP produced – ATP used = 4 - 2 = 2

Overall: 1 Glucose → 2 Pyruvate + 2 ATP + 2 NADH

Overview of glycolysis

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Biochemistry by Garrett and Grisham

Regulation of glycolysis

•  Phosphofructose kinase (reaction 3)

–  Is the most important control site in the mammalian glycolytic

pathway –  The activity of the enzyme depends on the ATP/AMP ratio

•  Hexosekinase (reaction 1)

–  The inhibition of phosphofructokinase leads to the inhibition of hexokinase

–  It is not the primary control site in glycolysis as glucose

6-phosphate is not solely a glycolytic intermediate In muscle, glucose 6-phosphate can also be converted into glycogen The phosphorylation of fructose 6-phosphate to fructose 1,6-

bisphosphate is unique in glycolysis

•  Pyruvate kinase (reaction 10)

–  ATP allosterically inhibits pyruvate kinase to slow glycolysis

when the energy charge is high

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Other substrates used in glycolysis

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Biochemistry by Garrett and Grisham

Metabolism of fructose

•  Diets containing large amounts of sucrose (a

disaccharide of glucose and fructose) can utilize the

fructose as a major source of energy

•  Fructose is found in foods containing sucrose (fruits),

high-fructose corn syrups, and honey

•  The pathway to utilization of fructose differs in muscle

and liver

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Metabolism of fructose in liver

•  In liver, dietary fructose is converted to Fructose-1-P by fructokinase (also in kidney and intestine)

•  Then, by the action of Fructose-1-P aldolase (aldolase B), Fructose-1-P is converted to dihydroxyacetone

phosphate (DHAP) and glyceraldehyde

•  Glyceraldehyde is converted to glyceraldehyde-3-P by triose kinase which together with DHAP may undergo:

–  Combine together and converted into glucose (main pathway) –  They may be oxidized in glycolysis

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Metabolism of fructose in liver

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Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt

Metabolism of fructose in liver

•  The affinity of fructose-1-phosphate adolase for fructose-1-P is much poorer than that of fructose-1,6-biphosphate, thus fructose-1-P accumulates in fructokinase-expressing tissues

•  Thus, fructose-1-phosphate adolase is the rate-limiting

enzyme for fructose metabolism

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Metabolism of fructose in muscle

•  Muscle which contains only

hexokinase can phosphorylate

fructose to fructose 6-phosphate

which is a direct glycolytic

intermediate

•  However, hexokinase has a very

low affinity to fructose compared

to glucose, So it is not a

significant pathway for fructose

metabolism Unless it is present

in very high concentration in

blood

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Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt

Is excess fructose harmful?

•  Fructose is used as a sweetener in soft drinks and other foods

•  F r u c t o s e c a t a b o l i s m i n l i v e r b y p a s s e s t h e phosphofructokinase-catalyzed step of glycolysis and thereby avoids a major metabolic control point

→ Disrupt fuel metabolism so that glycolytic flux is directed toward lipid synthesis in the absence of a need for ATP

metabolic-syndrome-driven-fructose-sugar-diet

http://www.ucsf.edu/news/2009/06/8187/obesity-and-gkdating.com

Metabolism of galactose

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•  The major source of galactose is lactose (a disaccharide

of glucose and galactose) obtained from milk and milk products

•  Galactose enters glycolysis by its conversion to

glucose-1-phosphate (G1P) This occurs through a

series of steps

Metabolism of galactose

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Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt

Disease related to metabolism of galactose

Disease related to metabolism of galactose

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•  Buildup of galatose in blood results in high concentration

of galactose in the crystalline lens of the eye→ gatactose

is reduced to gatatitol, presence of this sugar alcohol in the lens eventually causes cataract formation

Biochemistry, Tymoczko, Berge, Strayer

Disease related to metabolism of galactose

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•  Galactosemia is treated by a galactose-free diet

•  Elimination of galactose from the diet prevents liver disease and cataract development

•  The majority of patients still suffer from central nervous system malfunction, most commonly a delayed acquisition of language skills Female patients also display ovarian failure

Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt

Metabolism of mannose

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•  Mannose enters the glycolytic pathway after its

conversion to fructose 6-phosphate via a two-reaction

pathway:

Fundamentals of biochemistry-Life at the molecular level, Voet, Voet, Pratt

Artificial sweeteners are compounds that mimic sugars but not metabolized or contribute

a little to energy metabolism due to their low concentration

Oldest artificial sweetener

Sweet’n low

Break down to aspatate ; phenylalanine

Instable to heat or be hydrolyzed in soft drinks over time

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