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34 Cards in this Set
- Front
- Back
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Glycolysis
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uses central fuel = glucose
-central to carb metabolism, all tissue utilize to generate ATP from glucose -can be either: 1. anaerobic (lactate) 2. aerobic (pyruvate) |
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Importance of Anaerobic Glycolysis?
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-conversion of NADH into NAD+
-lactate hydrogenase -creates more NAD+ to keep step 4 of glycolysis running |
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Glycolysis Production:
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Invest: 2 ATP
Generate: 4 ATP * ATP drives cytosolic metabolic rxns -generate: 2 NADH: donates e- for ETC |
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Aerobic Glycolysis product?
Where does it go? |
Pyruvate
-converted into Acetyl-CoA->TCA Cycle -enzyme: pyruvate dehydrogenase complex (PDHC) -enters mitochondria (converted to Acetyl CoA)-->NADH, FADH2, GTP |
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3 main regulation sites of glycolysis
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1. glucokinase/hexokinase: glucose -> glucose-6-P
2. PFK: fructose-6-P -> fructose(1,6)bisP 3. Pyruvate Kinase: Phosphoenolpyruvate -> pyruvate |
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1st Regulated Step
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P of Glucose
Hexokinase: found in most tissues -low Km (high affinity for glucose) -low Vmax for glucose (high [glucose] = enzyme max out quickly) Glucokinase: liver & pancrease -high Km: P glucose at high [glucose], doesn't work well for low [glucose] -high Vmax |
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Which enzyme at the 1st regulated step is activated during low blood glucose?
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-don't want to store glucose
-glucokinase: inactive (liver & pancreas) -hexokinase: continues bc high affinity |
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2nd Regulated Step
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fructose-6-P --> fructose(1,6)BP
Phosphofructokinase-1 (PFK): MOST IMPORTANT -negative regulators: ATP, citrate (high energy state compounds) -Positive regulators: AMP, Fructose2,6BP (low energy) |
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Most Important Regulator of PFK-1
In the well-fed state what is the insulin:glucagon ratio |
*Fructose 2,6 BP*
-most potent activator of glycolysis increase insulin decrease glucagon -ratio high in fed state (storing) -ratio low in fasted state |
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Explain main regulation mxn of PFK-1.
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FASTED STATE
glucagon->binds receptor->Gs protein->adenylate cyclase (ATP->cAMP)->activate PKA(ATP->ADP)->bifxnal enzyme:FBP-2(active) phosphorylated FED STATE decreased PKA activity->dephosphorylates bifxnal enzyme-> PFX-2(active)->formation of fructose2,6BP->stim. glycolysis |
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3rd Regulated Step
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convert phospho-enolpyruvate->pyruvate
-catalyzed by pyruvate kinase -final step of glycolysis (ATP generating) -pyruvate kinase stim. by fructose1,6BP |
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Negative Regulation of PK
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pyruvate kinase shut off by phosphorylation
-want to turn off when blood glucose levels are low (want gluconeogenesis) |
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Hormonal Control of Glycolysis
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-insulin & glucagon
-each regulated steps of Glycolysis: stimulated by insulin & inhibited by glucagon -insulin: storage of energy when food abundant (fed) -gluagon: mobalize energy when food minimal (fast) |
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Maintain Blood Glucose
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-some tissues require continous supply of glucose
-BRAIN -3 main sources maintain blood glucose for these tissues: 1. dietary glucose 2. glycogenolysis 3. gluconeogenesis |
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Source of Blood Glucose
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-glycogen breakdown 1st mxn to maintain blood glucose during fasting
-Glycogen stored in liver & some kidney -after glycogen depleted, gluconeogenesis takes over |
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Epinephrine
Where do hormones most affect? |
-supporting role in glucagon
-apposes insulin -liver, adipose, muscle, & brain |
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Insulin
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-polypeptide hormone
-produced by beta-cells of islets of Langerhans (pancreas) -these cells make up 1-2% of pancreas -half-life=6minutes -very rapid degradation: transition to fed/fast state quickly |
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Insulin Structure
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-2 polypeptide chains (A chain & B chain)
-51 aa -A & B chain linked by 2 disulfide bridges -A chain has an intramolecular disulfide bridge -only cysteine aa can bind disulfide bonds |
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Insulin Synthesis
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-begins in cytosol
1. signal sequence aids in mvmt of ribosome to rough ER 2. Protein synth. pause until ribosome binds RER then continues 3. full length protein synth into RER (preproinsulin) 4. RER: the signal sequence is cleaved making: proinsulin 5. proinsulin moves to golgi where pro-portion cleaved->makes: insulin & C-peptide 6. both move to secretory granules await exocytosis |
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Regulation of Insulin Secretion
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-3 stimuli can increase beta-cell exocytosis of insulin:
1. glucose 2. aa (arginine) 3. GI hormones |
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True or False, and why?
Administration of 50g of glucose orally will induce a higher insulin release than 50g of glucose intravenously. |
true
intravenous: doesn't go thru GI tract (no GI hormone stim) orally: stimulates GI hormones (stimulates insuline release) |
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What hormone acts to inhibit insulin secretion?
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epinephrine
-NOT glucagon (released by pancreas but DOESNT act on pancreas) -both epi & glucagon signal thru G-protein linked receptors -insulin works thru diff type of receptor (tyrosine kinase) |
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What stimulates insulin secretion?
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-glucose & aa
-if consume exclusively protein: potential form of energy, insulin stim in response to all forms of energy |
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Metabolic Effects on Insulin
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Carb Metabolism:
-increase glycogen synth -increase GLUT-4 (glucose transport to muscle/adipose) -decrease glycogenolysis & gluconeogenesis (liver) Lipid Metabolism: -increase triacylglycerol synth (adipose/liver) -decrease hormone sens. lipase (adipose) Protein Metabolism: -incrase aa entry & protein synth (most tissues) |
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Insulin receptor
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-insulin binds w/ tyrosine kinase acitivity
-consists of 4 subunits held together by disulfide bonds in extracellular region -receptor tyrosine kinase of insulin is always dimerized |
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Insulin Signaling
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-insulin binds triggers receptor autophosphorylation
-leads to P of other proteins including other kinases & phosphatases (dephosphorylates proteins) |
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Glucagon
What stimulates? What inhibits? |
-secreted by alpha-cells of pancreas
-low glucose -plasma aa -epinephrine -high glucose -insulin |
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Inhibit Glucagon
Stimulate Glucagon Inhibit Insulin Stimulate Insulin |
GLUCAGON
+: epi & aa -: glucose & insulin INSULIN +: glucose & aa -: epi |
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Glucagon Signaling
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-binds to a receptor that stim. Gs signaling
-leads to increase in cAMP and PKA activity -most effects of glucagon are on liver cells (hepacytes) |
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Metabolic Effects of Glucagon
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Carb Metabolism:
-increase glycogen (only liver) -increase gluconeogenesis Lipid Metabolism: -incrase lipolysis (adipose) Protein metabolism: -increase aa uptake by liver |
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Overall what does insulin do?
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-increase: glucose uptake, glycogen synthesis, protein synthesis, fat sythesis
-decrease: gluconeogenesis, glycogenolysis, lipolysis *altered gene expression |
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Overall what does glucagon do?
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-increase: glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, uptake aa
-decrease: glycogenesis (glycolysis) |
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Epinephrine
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-2nd important counter-regulatory hormone in addition to glucagon
-effects primarily on peripheral tissues -synth predom from adrenal medulla: -inhibit insulin release (pancreas) & skeletal muscle glucose uptake -stimulate lipolysis (adipose) & glucagon release (pancreas) |
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Why epinephrine inhibits skeletal muscle glucose uptake?
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because primary goal for glucose during a fast is to get glucose to the brain, skeletal muscle secondary
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