Metabolism of saccharides - exercise -

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Metabolism of saccharides- exercise -

• Vladimíra Kvasnicová

2
Glucose enter the cells by

1. free diffusion
2. facilitated diffusion
3. active transport
4. secondary active transport

3
Glucose enter the cells by

1. free diffusion
2. facilitated diffusion
3. active transport
4. secondary active transport

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Insulin-dependent transport of glc into the cell
is found in the

1. liver
2. erytrocyte
3. adipose tissue
4. muscle

5
Insulin-dependent transport of glc into the cell
is found in the

1. liver
2. erytrocyte
3. adipose tissue
4. muscle

6
Glucose transport into cells facilitated
diffusion(protein transporter GLUT various
types)
ERYTROCYTES NERVOUS TISSUE -
insulin-independent transport
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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HEPATOCYTES - insulin-independent transport
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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FATTY TISSUE MUSCLES -
insulin-DEPENDENT transport insulin increases
number of glc transporters
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
9
Secondary-active transport of GLC symport with
Na - small intestine, kidneys
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
10
Glucose from a diet can be used

1. as an energy source for cells
2. for glycogen synthesis
3. for formation of fat ( energy store)
4. as a main substrate for production of NADPH

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Glucose from a diet can be used

1. as an energy source for cells
2. for glycogen synthesis
3. for formation of fat ( energy store)
4. as a main substrate for production of NADPH

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Glc-6-P !!!
NADPH
hepatocyte
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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Glycolysis( oxidative cleavage of glucose)

1. is located in a mitochondrion
2. can proceed under anaerobic conditions as well
3. produces 2 moles of pyruvate / 1 mole of Glc
4. generates 2 moles of ATP as a net energy
   acquisition

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Glycolysis( oxidative cleavage of glucose)

1. is located in a mitochondrion
2. can proceed under anaerobic conditions as well
3. produces 2 moles of pyruvate / 1 mole of Glc
4. generates 2 moles of ATP as a net energy
   acquisition

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Products of aerobic glycolysis
2
Products of anaerobic glycolysis
NADHwas consumed in conversion of pyruvate to
lactate
2
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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Enzyme hexokinase

1. catalyzes esterification of glucose
2. has higher affinity to glucose than glucokinase
3. phosphorylates fructose as well
4. is found in a cytoplasm of many cells

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Enzyme hexokinase

1. catalyzes esterification of glucose
2. has higher affinity to glucose than glucokinase
3. phosphorylates fructose as well
4. is found in a cytoplasm of many cells

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IRREVERSIBLE REACTION
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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Km Km
The glucokinase has higher value of Kmthan
hexokinase? glucokinase has lower affinity to
glucose (it needs more glucose to reach the
reaction velocity of Vmax/2)
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
20
Enzyme 6-phosphofructokinase-1 (PFK-1)

1. is a main regulatory enzyme of glycolysis
2. converts fructose-1,6-bisphosphate to
   fructose-6-phosphate
3. is activated by citrate and ? ATP/ADP
4. is regulated by insulin

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Enzyme 6-phosphofructokinase-1 (PFK-1)

1. is a main regulatory enzyme of glycolysis
2. converts fructose-1,6-bisphosphate to
   fructose-6-phosphate
3. is activated by citrate and ? ATP/ADP
4. is regulated by insulin

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IRREVERSIBLE REACTION
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
23
NADHH forming in glycolysis

1. is a coenzyme of oxidoreductases
2. can be reoxidized back to NAD in a conversion of
   pyruvate to lactate
3. can be used in a reduction of malate to
   oxaloacetate
4. is a source of reducing equivalents enteringa
   respiratory chain, but only under aerobic
   conditions

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NADHH forming in glycolysis

1. is a coenzyme of oxidoreductases
2. can be reoxidized back to NAD in a conversion of
   pyruvate to lactate
3. can be used in a reduction of malate to
   oxaloacetate
4. is a source of reducing equivalents enteringa
   respiratory chain, but only under aerobic
   conditions

25
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
26
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
27
Transport of reducing equivalents to mitochondria
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
MALATE-ASPARTATE SHUTTLE
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GLYCEROL PHOSPHATE SHUTTLE
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
29
2,3-bisphosphoglycerate (2,3-BPG)

1. belongs among energy rich compounds
2. is formed from glyceraldehyde-3-phosphate by
   phosphorylation using inorganic phosphate
3. can be transformed to 3-phosphoglycerate, ATP is
   simultaneously formed from ADP
4. is formed only in the liver as a shunt of
   glycolysis

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2,3-bisphosphoglycerate (2,3-BPG)

1. belongs among energy rich compounds
2. is formed from glyceraldehyde-3-phosphate by
   phosphorylation using inorganic phosphate
3. can be transformed to 3-phosphoglycerate, ATP is
   simultaneously formed from ADP
4. is formed only in the liver as a shunt of
   glycolysis

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2,3-BPG shunt
IN ERYTROCYTES 2,3-BPG ? affinity of Hb to O2
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
32
ATP is formed in the reactions of glycolysis

1. phosphoenolpyruvate (PEPA) ? pyruvate
2. glucose ? glucose-6-phosphate
3. fructose-1,6-bisphosphate? fructose-6-phosphate
4. glyceraldehyde-3-phosphate? 1,3-bisphosphoglycera
   te

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ATP is formed in the reactions of glycolysis

1. phosphoenolpyruvate (PEPA) ? pyruvate
2. glucose ? glucose-6-phosphate ATP is consumed
3. fructose-1,6-bisphosphate not energy-rich
   comp.? fructose-6-phosphate
4. glyceraldehyde-3-phosphate? 1,3-bisphosphoglycera
   te

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IRREVERSIBLE REACTION
substrate level phosphorylation (ATP formation
using energy released from cleavage of an energy
rich compound macroergic compound)
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
35
Pi
substrate level phosphorylation
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
36
Pyruvate can be transformed by

1. carboxylation to acetyl-CoA
2. reduction to lactate
3. oxidative decarboxylation to oxaloacetate
4. transamination to aspatate

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Pyruvate can be transformed by

1. carboxylation to acetyl-CoA
2. reduction to lactate
3. oxidative decarboxylation to oxaloacetate
4. transamination to aspatate

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transamination
reduction
carboxylation oxidative decarboxylation
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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Choose correct statements about regulation of
glycolysis

1. it is activated by insulin
2. it is activated by glucagon
3. regulatory enzymes of glycolysis are kinases
4. ? pH inhibits glycolysis

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Choose correct statements about regulation of
glycolysis

1. it is activated by insulin
2. it is activated by glucagon
3. regulatory enzymes of glycolysis are kinases
4. ? pH inhibits glycolysis

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Regulation of glycolysis
regulatory enzyme activation inhibition
hexokinase glucose-6-phosphate
glucokinase insulin (induction) fructose-1-phosphate (liver) fructose-6-phosphate
6-phosphofructo-1-kinase (PFK-1) main regulatory enzyme(key enzyme) ? ATP / AMP fructose-2,6-bisphosphate (? if ? insulin / glucagon) insulin (induction) ? ATP / AMP citrate acidic pH
pyruvate kinase insulin (induction) fructose-1,6-bisphosphate (feed foreward regulation) glukagon (repression, inhibition by phosphorylation) ? ATP / AMP acetyl-CoA
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Enzymes of gluconeogenesis( synthesis of
glucose de novo)

1. are found in a cytoplasm only
2. are active mainly in a brain and erytrocytes
3. are completely the same as enzymes of glycolysis
   (catalyze oposite reactions of glycolysis)
4. are not found in the liver

43
Enzymes of gluconeogenesis( synthesis of
glucose de novo)

1. are found in a cytoplasm only
2. are active mainly in a brain and erytrocytes
3. are completely the same as enzymes of glycolysis
   (they catalyze oposite reactions of glycolysis)
4. are not found in the liver gluconeogenesis
   proceeds only in the liver and the kidneys

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in mitochondria only
The figure is found at http//www.kumc.edu/resear
ch/medicine/biochemistry/bioc800/car02fra.htm
(lJan 2007)
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Gluconeogenesis
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
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Choose substrates of gluconeogenesis

1. acetyl-CoA
2. pyruvate
3. glycerol
4. lactate

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Choose substrates of gluconeogenesis

1. acetyl-CoA it can not be converted to pyruvate
2. pyruvate
3. glycerol
4. lactate

48
Cori cycle
and muscle
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
49
Glucose-alanine cycle
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
50
tuk
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
51
Choose enzymes of gluconeogenesis

1. pyruvate kinase
2. PEP carboxykinase
3. pyruvate carboxylase
4. pyruvate dehydrogenase

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Choose enzymes of gluconeogenesis

1. pyruvate kinase
2. PEP carboxykinase
3. pyruvate carboxylase
4. pyruvate dehydrogenase

53
Pyruvate DeHydrogenase complex is found in
mitochondria
(multienzyme complex, PDH) the reaction is
IRREVERSIBLE
The figure is found at http//faculty.uca.edu/joh
nc/pdhrxns.gif (Jan 2006)
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The reactions participate in gluconeogenesis

1. pyruvate CO2 ? oxaloacetate
2. pyruvate ATP ? phosphoenolypyruvate
3. fructose-1,6-bisphosphate ? fructose-6-phosphate
   ATP
4. glucose-6-phosphate ? glucose ATP

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The reactions participate in gluconeogenesis

1. pyruvate CO2 ? oxaloacetate
2. pyruvate ATP ? phosphoenolypyruvate
3. fructose-1,6-bisphosphate ? fructose-6-phosphate
   ATP
4. glucose-6-phosphate ? glucose ATP

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Gluconeogenesis is

1. activated by insulin
2. inhibited by citrate
3. activated by AMP
4. inhibited by glucagon

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Gluconeogenesis is

• activated by insulin
• inhibited by citrate
• activated by AMP
• inhibited by glucagon
• the opposite answers are correct

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Regulation of gluconeogenesis
regulatory enzyme activation inhibition
pyruvate carboxylase acetyl-Co A cortisol, glucagon (induction) insulin (repression)
phosphoenolpyruvatecarboxykinase cortisol, glucagon (induction) insulin (repression)
fructose-1,6-bisphosphatase cortisol, glucagon (induction) ? AMP / ATP fructose-2,6-bisphosphate (? if ? insulin / glucagon) insulin (repression)
glucose-6-phosphatase cortisol, glucagon (induction) insulin (repression)
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Metabolism of glycogen

1. is regulated by glycogen synthase and glycogen
   phosphorylase
2. is located in a cytoplasm
3. is regulated by insulin
4. proceeds on reducing ends of glycogen molecule

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Metabolism of glycogen

1. is regulated by glycogen synthase and glycogen
   phosphorylase
2. is located in a cytoplasm
3. is regulated by insulin
4. proceeds on reducing ends of glycogen molecule

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Metabolism of glycogen
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
62
During glycogen synthesis( glycogenesis)

1. Glc-6-P is transformed to UDP-6-glc
2. glycogen synthase participates in a formation of
   both ?(1?4) and ?(1?6) glycosidic bonds
3. a macroergic phosphate is consumed
4. is glycogen synthase activated by glucagon

63
During glycogen synthesis( glycogenesis)

1. Glc-6-P is transformed to UDP-6-glc
2. glycogen synthase participates in a formation of
   both ?(1?4) and ?(1?6) glycosidic bonds
3. a macroergic phosphate is consumed
4. is glycogen synthase activated by glucagon

64
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
65
During degradation of glycogen within cells(
glycogenolysis)

1. ?(1?6) glycosidic bonds are split by glycogen
   phosphorylase
2. glucose is transfered to phosphate glc-1-P is
   formed as a product of the degradation
3. ?(1?4) bonds are split hydrolytically
4. 1 ATP is consumed if 1 glc is released

66
During degradation of glycogen within cells(
glycogenolysis)

1. ?(1?6) glycosidic bonds are split by glycogen
   phosphorylase
2. glucose is transfered to phosphate glc-1-P is
   formed as a product of the degradation
3. ?(1?4) bonds are split hydrolytically
4. 1 ATP is consumed if 1 glc is released

67
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
68
If glycogenolysis is followed by glycolysis

1. the net gain of the anaerobic glycolysis is3 ATP
2. the process is called gluconeogenesis
3. both the cytoplasmatic and mitochondrial enzymes
   participate in the reactions
4. oxaloacetate is formed as an intermediate

69
If glycogenolysis is followed by glycolysis

1. the net gain of the anaerobic glycolysis is3 ATP
2. the process is called gluconeogenesis
3. both the cytoplasmatic and mitochondrial enzymes
   participate in the reactions
4. oxaloacetate is formed as an intermediate

70
glycogen
glucose
ATP ADP
Pi
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)
71
Regulation of glycogen metabolism
regulatory enzyme activation inhibition
glykogen phosphorylase (glycogen degradation) glucagon, adrenaline (phosphorylation) ? ATP / AMP Ca2 (muscle) ? ATP / AMP glucose-6-phosphate glucose
glykogen synthase (glycogen synthesis) insulin (induction) glucose-6-phosphate glucagon, adrenaline (phosphorylation)
72
Pentose cycle( Hexose MonoPhosphate Pathway,
HMPP)

1. is located in a cytoplasm
2. includes direct oxidation of glucose
   monophosphate
3. is a shunt of glycolysis (products of HMPP can
   enter glycolysis)
4. produces pentoses

73
Pentose cycle( Hexose MonoPhosphate Pathway,
HMPP)

1. is located in a cytoplasm
2. includes direct oxidation of glucose
   monophosphate
3. is a shunt of glycolysis (products of HMPP can
   enter glycolysis)
4. produces pentoses

74
The figure is found at http//www.richmond.edu/jb
ell2/14F34.JPG (Dec 2006)
75
Choose enzymes of HMPP

1. transketolase
2. transaminase
3. glucose-6-phosphate dyhydrogenase(glc-6-P DH)
4. pyruvate carboxylase

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Choose enzymes of HMPP

1. transketolase
2. transaminase
3. glucose-6-phosphate dyhydrogenase(glc-6-P DH)
   regulatory enzyme
4. pyruvate carboxylase

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Pentose cycle

1. produces NADPH which can be oxidized in a
   respiratory chain ? energy is produced
2. generates saccharides used in a glycoprotein
   synthesis
3. forms ribose-5-phosphate a substrate of nucleic
   acids synthesis
4. forms fru-6-P and glyceraldehyde-3-P which can
   enter glycolysis or gluconeogenesis

78
Pentose cycle

1. produces NADPH which can be oxidized in a
   respiratory chain ? energy is produced
2. generates saccharides used in a glycoprotein
   synthesis
3. forms ribose-5-phosphate a substrate of nucleic
   acids synthesis
4. forms fru-6-P and glyceraldehyde-3-P which can
   enter glycolysis or gluconeogenesis

79
If NADPH accumulates

1. oxidative part of HMPP is inhibited
2. ribose-5-phosphate can not be synhesized
3. glc-6-P dehydrogenase is activated
4. the reversible reactions of the HMPP can only
   proceed

80
If NADPH accumulates

1. oxidative part of HMPP is inhibited
2. ribose-5-phosphate can not be synhesized
3. glc-6-P dehydrogenase is activated
4. the reversible reactions of the HMPP can only
   proceed

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IRREVERSIBLE
The figure is found at http//web.indstate.edu/thc
me/mwking/pentose-phosphate-pathway.html (Dec
2006)
82
synthesis of nucleotides
REVERSIBLE
intermediates of glycolysis
The figure is found at http//web.indstate.edu/thc
me/mwking/pentose-phosphate-pathway.html (Dec
2006)
83
Regulation of HMPP

• on the level of substrates availability and
  products consumption
• ? NADPH / NADP
• reaction using NADP are inhibited by lackof the
  coenzyme

84
Fructose

1. is metabolized mainly in the liver
2. can be transformed to fru-6-P by fructokinase
3. can be formed from sorbitol as well
4. can be transformed to glucose

85
Fructose

1. is metabolized mainly in the liver
2. can be transformed to fru-6-P by fructokinase
3. can be formed from sorbitol as well
4. can be transformed to glucose

86
Metabolism of fructose in the liver
glycolysis or gluconeogenesis
The figure is found at http//web.indstate.edu/thc
me/mwking/glycolysis.html (Jan 2007)
87
The figure was adopted from Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
88
When Fru is converted to Fru-1-P

1. it can be split by an aldolase to glyceraldehyde
   and dihydroxyacetone phosphate
2. is fructose metabolised in glycolysis faster then
   glucose
3. glyceraldehyde made by spliting of fru-1-P can be
   converted to glycerol
4. glucokinase can be activated by fru-1-P

89
When Fru is converted to Fru-1-P

1. it can be split by an aldolase to glyceraldehyde
   and dihydroxyacetone phosphate
2. is fructose metabolised in glycolysis faster then
   glucose
3. glyceraldehyde made by spliting of fru-1-P can be
   converted to glycerol
4. glucokinase can be activated by fru-1-P

90
Glucose can be converted to

1. galactose glc-6-P ? gal-6-P
2. fructose glc ? glucitol ? fru
3. glucuronic acid UDP-glc 2 NAD ?
   UDP-glukuronate 2 NADHH
4. ribose glc-6-P ? ? ribulose-5-P ? rib-5-P

91
Glucose can be converted to

1. galactose glc-6-P ? gal-6-P
2. fructose glc ? glucitol ? fru
3. glucuronic acid UDP-glc 2 NAD ?
   UDP-glukuronate 2 NADHH
4. ribose glc-6-P ? ? ribulose-5-P ? rib-5-P

92
Metabolism of galactose
epimerization proceeds on the level of
UDP-derivatives
The figure is found at http//web.indstate.edu/thc
me/mwking/glycolysis.html (Jan 2007)
93
The figure is found at http//www.kumc.edu/researc
h/medicine/biochemistry/bioc800/car02fra.htm (Jan
2007)