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Basic and metabolism
of Carbohydrate
Donrawee Leelarungrayub (Ph.D. Biochem)
Department of Physical Therapy
Faculty of Associated Medical Sciences
Chiang Mai University, Chiang Mai, Thailand
E-mail; [email protected]
http://web.indstate.edu/thcme/mwking/home.html
Outline
Structure and function
Biochemical pathways and regulation
Overview
Glucose provides a significant portion and
the energy needed by cells in the fed
state.
 Glucose is maintained in the blood as the
sole energy source for the brain in the
nonstarving state and as an available
energy source for all other tissues.
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Monosaccharide = glucose, fructose, ribose
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Disaccharide = lactose, sucrose, maltose
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Oligosaccharide = blood group antigens, membrane
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Polysaccharide = starch, glycogen, glycosaminoglycan
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Monosaccharide derivatives
Sugar acid = ascorbic acid (VitC) = collagen synthesis
 Glucuronic acid + bilirubin = conjugated bilirubin (water soluble)
 Glucuronic acid => glycosaminglycan (GAGs) (extracellular matrix)
 Deoxy sugars = 2-deoxyribose (DNA)
Sugar alcohols
 Glycerol derived from triglycerol
 Sorbitol derived from glucose: cataract, peripheral neuropahty,
retinopathy == DM
Amino sugars = glucosamine (GAGs)
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Polysaccharides
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Sugar polymers
Starch
Glycogen
Cellulose
Hyaluronic acid and other GAGs
http://138.192.68.68/bio/Courses/biochem2/Glycogen/Glycogen.html
Transferase
Oxidoreductase
Hydrolase
Lyase (Synthase)
Isomerase
Ligase
http://fig.cox.miami.edu/~cmallery/255/255enz/ES_complex.jpg
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Glycolysis:
TCA cycle (Krebs cycle)
Glucose > pyruvate > Acetyl CoA
Acetyl CoA, (intermediates,reducing
agent)
Pentose phosphate pathway
Gluconeogenesis
NADPH, ribose
Glycogen degradation
Glycogenesis
G-6-P , TCA cycle
Electron transport chain/
oxidative phosphorylation
ATP
PEP, F-6-P, G-6-P (Lactate, Glycerol,
Amino acid)
Glycogen
Carbohydrate absorption
- Monosaccharide
- Galactose and Glucose (fast absorption) with sodium-dependent glucose
transport (SGLT) : active transport
- Another sugar (facilitation diffusion)
Lastase
Lactose
Galactose
Amylase
Starch
Sucrose
Na+
Maltose
Maltotriose
Dextrin
Sucrase
Glucose
SGLT
Glucose
Galactose
Fructose
Glucose uptake
- Transport proteins (Glucose transporter 1-7)
- Facilitative glucose transport , Na+-dependent glucose transport
Glycogen
Glycogen
phosphorylase
Pi
D- Glucose -1-P
Phosphoglucomutase
D- Glucose -6-P
Glucose-6-phosphorylase
(only Liver)
TCA
Glucose
H 2O
Pi
Pentose Phosphate Pathway
Enzymes are in cytoplasm
- RBC
- Platelet
- Muscle (Fast-twitch fiber)
- 2 mol ATP/1 mole Glucose
Hexose
Anaerobic pathway
Pyruvate DH
All tissue
Liver, pancreatic
Malate aspartate shuttle
Glycerol phosphate shuttle
Pyruvate deghydrogenase
Lactate
Pyruvate deghydrogease ( multienzyme complex)
Active form (nonphosphate) insulin, ADP
Inactive form (phosphate), acetyl CoA, NADH
PPP
insulin
(-) ATP
(+) AMP
(+) F 1,6-biphosphate
Pyruvate deghydrogenase
Lactate
PPP
Amino sugar
triacyleglycerols
2,3,-BPG in RBCs
Pyruvate deghydrogenase
Lactate
Gluconeogenesis

Glucose synthesis by outside source
 Lactate; cori cycle in RBC
 Glycerol from FA degradation
 amino acid; glucogenic amino acid
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Four key enzymes
 Pyruvate
carboxylase
 Phosphoenolpyruvate (PEP) carboxykinase
 Fructose 1,6-biphosphatase
 Glucose 6-phosphatase
Regulation
- acetyl CoA => + pyruvate decarboxylase
- insulin/glucagon ratio  pyruvate kinase
F2,6-biphosphatase
Stimulators; G-6-P, ATP, Insulin
Inhibitors; Ca2+, ADP, Glucagon, Epinephrine,
Norepinephrine, Glucocorticoids
D- Glucose
Glucokinase (liver)
Mg2+
Hexakinase (liver, muscle)
ATP
ADP
D- Glucose -6-P
Phosphoglucomutase
D- Glucose -1-P
Glucose-1-P- uridyltransferase
UDP
Glycogen synthase
(rate-limiting enzyme)
UTP
UDP
UDP-Glucose
(Glucose)n- Glycogenin
(Glucose)n+ Glycogen
(glycogenin – (1-4) -glucose
http://www.scienceinschool.org/2006/issue1/diabetes/
Glycogen metabolism: regulated steps
High insulin : Low glucagon
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Fed state
Promotes glycogen syn.
+ hepatic protein
phosphatase,
dephosphate glycogen
synthase
Low insulin: High glucagon
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Fasting state
+ adenylate cyclase,
+ protein kinase A
+ phosphorylase kinase
=> glycogen degradation
in the liver
Pentose Phosphate Pathway
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Three irreversible reactions:
glucose-6-phosphate > ribulose 5-phosphate and CO2, NADPH
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>> ribose -5- phosphate and intermediates (glycolysis
and gluconeogenesis)
Ribose 5-phosphate >> RNA & DNA synthesis
NADPH biosynthetic pathway
>> maintain GSH and Lipid synthesis
 G6PD deficiency
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D- Glucose
Mg2+
ATP
ADP
D- Glucose -6-P
Fructose-6-P
Fructose-1,6-BP
DHAP
GA-3-P
G-6-PH
6-Phosphogluconolactone
6-Phosphogluconate
NADP+ NADPH
Ribulose 5-P
Xylulose-5-P
Glyceraldehyde 3-P
Erythrose-4-P
Ribose-5-P
Sedoheptulose 7-P
Fructose 6-P
Why is the NADPH importance in the cell?
Precursor of nucleic acid synthesis
 Precursor of lipid synthesis
 Reducing agent of Glutathione
(antioxidant)
 Intermediate of ribose-5-phosphate for
amino acid synthesis
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Kerb Cycle
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TCA cycle;
reducing equivalents production => NADH, FADH2,
 CO2 Production to buffer
 intermediates to protein and lipid synthesis
 precursor of glucose, protein and nucleic acid
synthesis
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Regulation of Krebs Cycle
substrate availability -
mass action
allosteric inhibition - end product
covalent modification - reversible phosphorylation...
(protein kinases & phosphoprotein phosphatases)
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key enzymes
- PDH
- citrate synthetase
- isocitrate dehydrogenase
- alpha-keto gluatarate dehydrogenase
Electron Transport Chain
How NADH is intaken in mitochondria?
Regulation of Pathways
Enzyme regulation: Glycogen synthase
and Glycogen phosphorylase
 Hormone regulation:
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Glucagon (liver) and Epinephrine (adrenaline)
and Norepinephine (muscle)
 Insulin (beta-cell)
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ATP/ADPi or NADH/NAD+ ratio
ATP
&
Muscle Contraction
Glycoprotein and Proteoglycans
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Glycoprotein = short, braned oligosaccharide (blood group
antigen, cell-cell adhesion, coagulation factors)
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Proteoglycan = long, linear polysaccharide
(glycosaminoglycans)
Glycoprotein
Blood-group antigens on RBCs
 Laminin in basement membrane
 Fibronection : cell-surface receptors
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Proteoglycan
Extracellualr matrix, collagen, elastin
 Core protein + glycosaminoglycan (GAGs)
 GAGs
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Hyaluronic acid : synovial fluid
 Haparin: anticoagulant
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 Prevent
excessive fibrin formation during
inflammation
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Released by mast cells and basophils
+ anti-thrombin III activity (Factor XII, XI, X)
Heparan sulfate : plasma membrane
 Chondroitin sulfate: osteoarthritis
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1. Lactase deficiency
2. Insulin-secreting tumors
3. Diabetes mellitus (DM)
http://www.scienceinschool.org/2006/issue1/diabetes/
4.
5.
6.
7.
G-6-PD (glucose 6-phosphate dehydrogenase) deficiency
Mitochondrial DNA mutation
Glycogen storage disease
Glucose metabolism during exercise