Transcript 0495116572_102921

Chapter 3
Carbohydrates
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Structural Features
• Simple carbohydrates
– Monosaccharides
– Disaccharides
• Complex carbohydrates
– Oligosaccharides
– Polysaccharides
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Simple Carbohydrates
• Monosaccharides
– Steroisomerism
• Chiral carbon - have 4 different atoms or
groups attached to them
• Stereoisomers - have 2 or more chiral
carbon atoms with same 4 groups
attached but are not mirror images of
each other
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Simple Carbohydrates
– Ring structures - molecules cyclize &
form another chiral carbon
– Haworth models
– Pentoses
– Reducing sugars
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Simple Carbohydrates
• Disaccharides
– Maltose
– Lactose
– Sucrose
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Complex Carbohydrates
• Oligosaccharides
– Raffinose
– Stachyoses
– Verbascose
• Polysaccharides
– Starch
– Glycogen
– Cellulose
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Digestion
• Polysaccharides
– Salivary -amylase - mouth
– Pacreatic -amylase - small intestine
– Resistant starches
• Digestion of disaccharides
– Disaccharidases - active in microvilli
of enterocytes
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Absorption, Transport, &
Distribution
• Absorption of glucose & galactose
– Into cell: active transport - SGLT1
– Into blood: diffusion, GLUT2
• Absorption of fructose
– Into cell: facilitated transport - GLUT5
– Into blood: GLUT2
– Limited in 60% of adults
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Absorption, Transport, &
Distribution
• Monosaccharide transport &
cellular uptake
• Glucose transporters
– GLUT isoforms
• Integral proteins
• Each has specific combining site
• Undergoes a conformational change upon
binding the molecule
• Can reverse this change when unbound
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Absorption, Transport, &
Distribution
– Specificity of GLUTs
• GLUT1 - basic supply of glucose to cells
• GLUT2 - low infinity transporter; glucose
from enterocyte to blood
• GLUT3 - high-affinity for brain & other
glucose-dependent tissues
• GLUT4 - insulin sensitive, in muscle &
adipose tissues
• GLUT5 - for fructose
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Absorption, Transport, &
Distribution
• Insulin
– Role in cellular glucose absorption
• Binds to membrane receptor
• Stimulates GLUT4 to move to membrane
• Maintenance of blood glucose
levels
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Glycemic Response to
Carbohydrates
• Glycemic index
– Increase in blood glucose during 2hour period after consumption of a
certain amount of CHO compared
with equal CHO from reference food
• Glycemic load
– GI x g of CHO in 1 serving of food
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Integrated Metabolism in
Tissues
• Glycogenesis
– Conversion of glucose to glycogen
• Glycogenolysis
– Breakdown of glycogen to glucose
– Phosphorolysis process
– Regulation of phosphorylase
• Covalent - glucagon, epinephrine
• Allosteric - AMP
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Integrated Metabolism in
Tissues
• Glycolysis - degradation of glucose
to pyruvate
– Hexokinase/glucokinase reaction
– Glucose phosphate isomerase
– Phosphofructokinase reaction
– Aldolase reaction
– Glyceraldehyde 3-phosphate &
dihydroxyacetone phosphate
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Integrated Metabolism in
Tissues
– Oxidation of glyceraldehyde 3-phosphate to
carboxylic acid, incorporation of inorganic
phosphate into high-energy anhydride bond
– Substrate-level phosphorylation of ADP
– Phosphoglyceromutase
– Dehydration of 2-phosphoglycerate
– Phophoenolpyruvate (PEP) donates
phosphate group to ADP
– Lacate dehydrogenase reaction
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Integrated Metabolism in
Tissues
– Fructose enters pathway
– Galactose is phophorylated
– Galactose 1-phosphate converted to
glucose 1-phosphate
– Glucose 6-phosphate enters
hexosemonophophate shunt
– Glucose 1-phosphate enteres
glycogenesis
– Glucose can enter glycolysis
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Integrated Metabolism in
Tissues
• Substrate-level phosphorylation
• The tricarboxylic acid cycle
– TCA pathway
• Formation of citrate from oxaloacetate & acetyl
CoA
• Isomerization of citrate to isocitrate
• Dehydrogenation catalyzed by isocitrate
dehydrogenase
• Decarboxylation & dehydrogenation of ketoglutarate
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Integrated Metabolism in
Tissues
• Hydrolysis of thioester bond of acetyl CoA drives
phosphorylation of guanosine diphosphate (GDP)
• Succinate dehydrogenase reaction
• Fumerase incorporates H2O across double bond of
fumarate to form malate
• Malate converted to oxaloacetate
– ATPs produced by complete glucose
oxidation
• C6H12O6 + 6O2  6CO2 + 6H2O + energy
• Yields 12 ATPs + 2 mol acetyl CoA per 1 mol
glucose = 24 ATPs
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Integrated Metabolism in
Tissues
– Acetyl CoA oxidation and tricarboxylic
acid cycle intermediates
– NADH in anaerobic & aerobic
glycolysis: the shuttle systems
• Glycerol 3-phosphate shuttle system
• Malate-aspartate shuttle system
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Integrated Metabolism in
Tissues
• Formation of ATP
– Biological oxidation & the electron
transport chain
• Electron transport chain = sequential
reduction-oxidation
• Oxidative phosphorylation = oxidation of
a metabolite by O2 through electron
transport + phosphorylation of ADP
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Integrated Metabolism in
Tissues
– Anatomical site for oxidative
phosphorylation
– Components of the oxidative
phosphorylation chain
• Complex I NADH-coenzyme Q
oxidoreductase
• Complex II
• Complex III coenzyme Q-cytochrome c
oxidoreductase
• Complex IV
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Integrated Metabolism in
Tissues
– Phosphorylation of ADP to form ATP
– Translocation of H+
– ATP synthase
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Integrated Metabolism in
Tissues
• The hexosemonophosphate shunt
(pentose phosphate pathway)
– Pentose phosphates
– Reduced cosubstrate NADPH
• Gluconeogenesis
–
–
–
–
Synthesis of glucose from non-CHO
Reversal of glycolytic pathway
Lactate utilization
Efficient glycogenesis
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Regulation of Metabolism
• 4 mechanisms:
– Negative or positive modulation of
allosteric enzymes
– Hormonal activation by covalent
modification/induction
– Directional shifts in reactions
– Translocation of enzymes within cells
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Regulation of Metabolism
• Allosteric enzyme modulation
– AMP, ADP, & ATP as allosteric
modulators
– AMP’s positive modulation
• Causes shift from inactive to active form
of phosphorylase b
• Stimulates phosphofructokinase
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Regulation of Metabolism
• Regulatory effect of NADH:NAD+
ratio
• Hormonal regulation
– Glycolytic enzymes
– Bifunctional enzymes
– Gluconeogenic enzymes
• Directional shifts in reversible
reactions
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Perspective 3
Hypoglycemia:
Fact or Fall Guy?
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Hypoglycemia
• Preprandial vs. postprandial serum
glucose levels
• Types:
– Fasting hypoglycemia
• Usually caused by insulin, sulfonylureas
– Fed (reactive) hypoglycemia
• Impaired glucose tolerance, idiopathic
postprandial syndrome
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