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Dangers of Sugar Consumption |
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-above 25%=decrease in Calcium, magnesium, zinc and iron -added fructose increases BP and insulin resistance |
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-3-9 carbon atoms -hydroxyl groups (bind other groups) -carbonyl group (aldehyde or ketone); carbonyl carbon most active -contain chiral centers |
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-farther from carbonyl/anomeric carbon -four different atoms attached -determines L (opposite) vs. D (same) |
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alpha: OH below plane of ring beta: OH above plane of ring |
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-found naturally in few foods -product of starch digestion (starch->amylopectin->glucose) |
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not found in foods, by product of digestion |
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-2-10 monosaccharides -disaccharide most abundant -contain glycosidic bonds (alpha=digestible, beta=non-digestible) |
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-beta 1,2 linkage; non-digestible -lowers pH in gut by production of SCFA; kills pathogenic bacteria -low pH keeps ammonia in gut instead of blood stream; important in advanced liver disease -bulks stool |
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butyrate, acetate and proprionate |
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-Olestra -sucrose with 6-8 SCFA -not recognized by lipase or amylase -can cause anal leakage |
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-Splenda -3 OH replaced with Cl -becomes 600x sweeter |
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-55-65% fructose to glucose -metabolized in liver and enters below first key step in glycolysis (glucose->glucose-6-fructose) -causes build up of glyceraldehyde-3-P which contributes to TG and FA -lowers HDL and disrupts uric acid synthesis which increases BP |
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-glucose hydrolyzed from corn starch -used in IV |
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-over 10 mono -can be digestible or not -has reducing (can donate e-) or non-reducing ends (can't donate e-) |
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-70% amylopectin (branched) and 30% amalose -used to thicken liquids |
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-alpha 1,4 and 1,6 linkages -digestible |
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-non-digestible -beta 1,4 -bulks up stool and exercises colonic muscles |
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-alpha 1,2 and 1,4; somewhat fermentable -releases SCFA which decreases pH; energy source for colonisides and maintain healthy colon wall -SCFA also shut down enzymes in cholesterol synthesis |
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-salivary amylase: alpha 1,4, operates in pH=7 -inactivated in stomach (too acidic) -continues in neonates b/c pancreatic amylase doesn't develop until 6 mths. |
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-chyme enters deodenum->secretin and CCK release -Secretin causes pancreas to release bi-carbonate and CCK, amylase |
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-digests 90% oligo into dextrins, maltriose and maltose -binds to 5 glucose molecules and breaks between 2nd and 3rd molecule -alpha 1,4 specific -cannot digest alpha 1,6 |
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Principle Substrate: sucrose, malto-oligo (alpha 1,4 only) Km=18 (S) and 3 (M) |
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Principle Substrate: alpha dextrins (alpha 1,4 and 1,6) Km=2-4 |
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Principe Substrates: malto-oligosaccharides, alpha dextrins (alpha 1,4 only) Km=1-4(M) and 1 (D) |
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Principle Substrate: Trehalose Km=3 |
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Beta-Galactosidase Lactase |
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Definition
Principle Substrate: Lactose Km=2 |
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-transfers glucose (or galactose) and Na (cotransport) -on apical membrane -Na is removed from enterocyte via Na/K Pump (2 come out, 3 K come in) -against concentration gradient |
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-found in liver, pancreatic beta cells, basal lateral surface of SI, kidney -promotes absorption from enterocyte into portal circulation -low affinity for mono, so need very high concentration for activation -when levels are low, liver doesn't need, so goes to brain and RBC instead -uses facilitated diffusion and doesn't discriminate between mono |
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-found in SI, testes and kidney -transports fructose from lumen into enterocyte -uses passive diffusion (no energy use); moves downstream |
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-found on RBC, brain and low levels on all cells |
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-found on brain and low levels on all cells |
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-found on heart, muscle, adipose tissue and brain -dependent on insulin -transported via vesicles stimulated by insulin -translocation of genes into vesicles which are released in the presence of insulin |
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-taken in via GLUT4 which is activated by insulin -hexokinase catalyzes transformation from glucose to glucose-6-phosphate -glucose trapped in muscle because glucose-6-phosphate can't be dephos |
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-enters via GLUT2 which requires very high concentrations to be active -Glucokinase catalyzes transformation of glucose to glucose-6-phosphate; positively effected by insulin -glucose can move back out via glucose-6-phosphotase |
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1. Availability of substrate 2. Activity of key enzymes |
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Mechanisms of Enzyme Control |
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Definition
1. Allosteric Modification 2. Covalent Modification 3. Gene Expression |
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-pathway intermediates that either aid or inhibit enzyme activity -positive (T->R) or negative (R->T) effectors -catalyze non-reversible rxns -moderated by ATP and NAD) |
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-reversible phosphorylation -phosphate binding increases or decreases activity -occurs b/c of hormonal changes -mediated by kinase and phosphatases -reversible |
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-slow acting through transcription or translation -induction: increase mRNA transcription or translation at ribosome |
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Key Control Point for Blood Sugar |
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-High insulin -Low glucagon -Liver: decreases glycogenolysis decreases gluconeogenesis decreases glycogen synthesis -decreases glucose output by liver and decreases plasma glucose |
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conversion of glycogen polymers to glucose monomers |
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produces glucose from non carbohydrate sources such as lactate and AA |
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storage form of glucose in liver and muscles |
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-low insulin levels -high glucagon levels -Liver: increase glycogenolysis, gluconeogenesis; decreases glycogen synthesis -Leads to increase in hepatic glucose output and increased plasma glucose |
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hormone secreted from pancreas that raises blood glucose levels; opposite function of insulin |
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Glucose Metabolism in Liver |
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-stores excess glucose as glycogen -converts glucose to pyruvate -releases glucose to other tissues via gluconeogenesis and glycogenolysis |
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RBC and Glucose Metabolism |
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-no mitochondria -rely on glycolytic pathway for energy -requires oxygen |
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Brain and Glucose Metabolism |
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-can completely oxidize glucose under aerobic conditions |
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Muscle and Glucose Metabolism |
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-oxidize glucose and store for its own use |
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Adipose and Glucose Metabolism |
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can completely oxidize glucose at low levels; uses glucose |
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-10 sequential steps that yields 38 possible ATP -Pyruvate: 24 ATP -2 ATP -NADH: 6 ATP -Glucose (if oxidized): 6 ATP -generates glucose-6-phosphate for glycolysis, glycogen synthesis and pentose phosphate pathway |
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Glucose->glucose-6-phosphate->fructose-6-phosphate->fructose-1-6-phosphate->glyceraldehyde-3-phosphate->1,3-bisphosphoglycerate->3-phosphoglycerate->2-phosphoglycerate->phosphoenolpyruvate->pyruvate->lactate and ATP |
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-catalyzes transformation of glucose to glucose-6-phosphate -high Km for glucose (needs lots of substrate) -inactive when bound to regulatory protein (GKRP) -high fructose-1-phosphate and low fructose-6-phosphate causes GKRP to dissociate and GK to become active -fructose-1-phosphate only exists when fructose is high -induced by insulin |
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-high Km for glucose-6-phosphate (need lots of substrate) -clips phosphate so glucogen can be used as glucose -repressed by insulin and induced by cortisol (genetic) |
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-requires ATP and magnesium -catalyzes transformation of fructose-6-phosphate to fructose-1-6-diphosphate (F16P2) -first committed step of glycolysis -induced by insulin and repressed by glucagon -Positive Effectors: AMP/ADP, Fructose 2,6 diphosphate -Negative Effectors: ATP, citrate |
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Fructose 1,6 Diphosphatase |
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Definition
-catalyzes conversion of fructose-1-6-diphosphate to fructose-6-phosphate -induced by glucagon and repressed by insulin -Negative Effector: AMP/ADP, fructose 2,6 diphosphate |
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-synthesis and degredation determined by 6PF-2K or F2,6Pase respectfully -modified covalently |
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-occurs during fasting -glucagon binds to receptor and causes dissociation of G alpha complex from G protein via GDP->GTP -G alpha complex binds to adenylate cyclase which increases cAMP -cAMP activates protein kinase A by binding to regulatory units -Protein Kinase A phosphorylates bifunctional enzyme which inhibits 6PF-2K and activates F2,6Pase -favors gluconeogenesis over glycolysis |
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-occurs during fed state -Insulin binds to receptors and activates secondary messengers that phosphorylate many proteins including phosphodiesterase (decreases cAMP) and protein phosphatase -binding of insulin causes change in beta transmembrane protein -activates tyrosine residues which autophosphorylate and serve as docking points for relay proteins that phosphorylate phosphodiesterase and protein phosphatase -protein phosphatase dephosphorylates bifunctional enzyme and activates 6PF-2K and inhibits F2-6Pase -favors glycolysis over gluconeogenesis |
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-need ADP -catalyzes transformation of phosphoenolpyruvate to pyruvate -only found in mitochondria -Positive effectors: F-1-6P2 -Negative effectors: ATP, acetyl coA, alanine -Induced by insulin |
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Pyruvate Carboxylase and Phosphoenolpyruvate carboxykinase |
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Definition
-catalyze rxn of pyruvate to phosphoenolpyruvate and OAA -needs ATP, CO2, biotin and GTP -products are needed in more than one pathway -Positive Effector: Acetyl CoA (PC) -PEPCK induced by glucagon and repressed by insulin (use similar mechanism as 6FP-2K/F2-6Pase (PEPCK uses G protein and PK uses second messenger) |
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-changed to OAA in mitochondria using PC -OAA converted to aspartate, malate and PEP -crosses into cytosol through the use of ADH, MDH and PEPCK -ADH and MDH release NADH to keep gluconeogenesis going |
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Structural and Metabolic Differences between HFCS and sucrose |
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Definition
-HFCS contains glucose and fructose monomers vs. sucrose is a dissacharide -HFCS monomers don't need to be broken down vs. sucrose that must be cleaved |
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Metabolic Effects Associated with High HFCS Intake |
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Definition
1. Dyslipidemia 2. Hyperuricemia 3. Insulin Resistance 4. Appetite changes associated with weight gain |
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Uric Acid Formation from Fructose |
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Definition
-when fructose is changed to F-1-P it releases ADP, AMP and uric acid |
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Definition
AMP->IMP->Inosine->hypoxanthine->xanthine->urate |
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-acts as primer for growing chain on glycogen -has glucosyl transferase: catalyzes bond between glucose and glycogen -glucose linked via alpha 1,4 and 1,6 bonds at branched points |
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Glycogen Synthesis in Liver |
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Definition
Glucose->G-6-P->G-1-P->glycogen primer->elongation using 2 UDP=glycogen |
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-UDP-glucose gives up glucose to non-reducing end -forms alpha 1,4 glycosidic bond -branching enzyme takes over and cleaves a bond 4-6 units from branch point -forms alpha 1,6 bond which provides new site for elongation |
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Milk: 12 Bread/Cereal: 15 Vegetables: 5 Fruit: 15 Deserts: 15 |
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Guidelines for Sugar Consumption |
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Dietary Guidelines for Americans: 6% Institute of Medicine: no more than 25% World Health Organization: no more than 10% Average teen: 16% |
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Formed by rxn of hydroxyl group of C-5 with anomeric carbon on C-1 |
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specific for alpha 1,4 bonds |
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Amylase Digestion Products |
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dextrins, maltriose and maltose |
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as we get older we consume less lactose and lactase decreases as a result |
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Range of Normal Blood Sugar |
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Eventually turns into triglyceride backbone via glycerol-3-phosphatase |
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Uses of Glucose-6-Phosphate |
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Definition
-glycolysis -glycogen synthesis -pentose phosphate pathway (ribose 5 phosphate synthesis) |
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