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104 Cards in this Set
- Front
- Back
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Why is glycolysis important?
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It gives you the ability to acquire energy from glucose
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What is the brain's only (essentially) source of energy?
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Glucose (75-80% of glucose in body)
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What is the liver's most important role in metabolism?
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To deliver glucose to the blood or to regulate glucose homeostasis
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What are glucose transporters called?
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GLUT (GLUT1-GLUT5)
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Glucose transporter for intestine, kidney, LIVER, BETA-CELLS; mediates increase in glucose uptake, therefore called "glucose sensor"
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GLUT2
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Glucose transporter in insulin sensitive tissures, ADIPOSE, SKELETAL MUSCLE; mobilization to surface induced by insulin
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GLUT4
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Glucose transporter in neurons, which has lowest Km, therefore allowing neurons to have first choice of blood glucose
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GLUT3
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Diffusion
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Molecules moving down their concentration gradient; no regulation
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Facilitated Diffusion
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Molecules moving down their concentration gradient using transport proteins
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uniporters
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transport proteins which move one molecule at a time
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symporters
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transport protein which transports two molecules at a time, both in the same direction
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antiporter
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transport protein which transports two molecules at a time, in opposite directions (only for active transport)
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active transport
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energy (either primary from ATP, or secondary from electrochemical gradient) is used to transport molecules against their concentration gradient
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Priming Stage of Glycolysis
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Phosphorylation of glucose to glucose-6-phosphate
Phosphorylation of F6P to F16BP |
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Hydrolysis Stage of Glycolysis
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Cleavage of F16BP to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (DHAP)
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Oxidoreduction-Phosphorylation
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"Payoff Phase"
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Hexokinase
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An enzyme which can phosphorylate 6-carbon sugars
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Glucokinase
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A type of hexokinase which is specific for glucose only
Only present in Beta-Cells |
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PFK-1
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Rate limiting enzyme in glycolysis
Phosphorylates F6P to F16BP, using 1 ATP |
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Km
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Concentration of substrate when an enzyme is at 1/2 of maximum velocity
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How does glucose get back into blood from skeletal muscle?
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It can't
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Why is Glucokinase better for liver cells than hexokinase?
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hexokinase is quickly saturated (low Km), which means that it will quickly phosphorylate as much glucose as it can get ahold of. SInce phosphorylated glucose cannot leave the cell through the transporter, little glucose would get to the rest of the body.
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AVERAGE Resting Blood Glucose
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5mmol/L=100mg/dL
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Steady State Assumptions (3)
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1. ES complex remains constant during the initial phase of a reaction
2. Under saturating conditions, all E is in ES complex 3. If all enzyme in ES, the rate of product formation is maximal |
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What does low Km mean?
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more efficient conversion of substrate to product
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Competitive Inhibition
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Inhibitor binds at substrate site
Vmax unchanged, Km increased |
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Non-competitive Inhibition
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Inhibitor binds at site other than substrate site
Vmax decreased, Km unchanged |
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Un-competitive Inhibition
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Inhibitor only binds to ES complex, because binding site only becomes available when substrate is bound
Km and Vmax decreased |
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Lineweaver-Burk Plots
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plot of inverse of michaelis menten equation
x=0 ------>1/Vmax y=0 ------>-1/Km |
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What type of process is glycolysis?
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Oxidation process
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Where in the cell do the reactions of glycolysis occur?
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In the cytosol
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What is the rate-limiting enzyme of glycolysis?
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Phosphofructokinase-1 (PFK1)
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What is NADH?
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a reduced electron carrier
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In glycerol phosphate shuttle, how is the energy transported into the mitochondrion?
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NADH reduces DHAP to Glycerol-3-P, which then reduces FAD across inner mitochondrial membrane
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Why is the glycerol phosphate shuttle so important in adipose tissue?
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adipose tissue doesn't have the enzyme to convert glycerol-3-Phosphate into DHAP
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What are the Liver function test enzymes?
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AST
(aka aspartate transaminase; aka serum glutamic oxaloacetic transaminase; aka SGOT) ALT (aka alanine transaminase; aka serum glutamic pyruvic transaminase; aka SGPT) |
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Mass Action Principle
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The faster you get rid of product, the faster the reaction runs
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What difference is there between the glycerol phosphate pathway and the malate-aspartate shuttle
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GPP - FADH2 as final reduced electron carrier
MAS - NADH as final reduced electron carrier |
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to what is glucose metabolized in the brain?
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complete to carbon dioxide
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to what is glucose metabolized in the liver?
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complete to carbon dioxide
lactic acid diverted to fat deliver glucose to blood |
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to what is glucose metabolized in adipose tissue?
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to acetyl-CoA and then to fat
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to what is glucose metabolized in muscle?
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complete to carbon dioxide
lactic acid |
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to what is glucose metabolized in erythrocytes?
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lactic acid
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what is the most important role of the liver in metabolism?
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regulates glucose homeostasis
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what are the three stages of glycolysis?
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priming (activation via phosphorylation)
hydrolysis (into two 3-carbon molecules) oxidoreduction-phosphorylation (energy output) |
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what is the difference between glucokinase and hexokinase?
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glucokinase phosphorylates ONLY glucose and is found only in beta-cells of the pancreas (also has a higher Km than other hexokinases)
hexokinase phosphorylates any 6-carbon sugar and is ubiquitously expressed |
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what is DHAP?
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dihydroxyacetone phosphate
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what enzyme hydrolyzes fructose-1,6-bisphosphate?
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aldolase
(aldolase A) |
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what is important about the glycerol phosphate shuttle in adipose tissue?
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it doesn't happen in adipose tissue because adipocytes lack glycerol kinase so they cannot metabolize the glycerol produced during triacyl glycerol degradation; it is instead shuttled to the liver via the blood
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what is OAA?
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oxaloacetic acid
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what regulates the malate-aspartate shuttle and the glycerol phosphate shuttle?
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as [ATP] increases, [NADH] increases, so the process is slowed down
as [ATP] decreases, [NADH] decreases, so the process speeds up |
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at what three enzymes is glycolysis regulated?
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hexokinase
phosphofructokinase-1 (PFK-1) pyruvate kinase |
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how is the regulation of glucokinase different from that of hexokinase?
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hexokinase is product inhibited by glucose-6-phosphate, whereas glucokinase is unregulated
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what are the allosteric activators of PFK-1? the allosteric inhibitors?
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activators: AMP, F2,6BP
inhibitors: ATP, citrate |
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where is citrate produced? how does it inhibit PFK-1?
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produced in the mitochondria via the TCA cycle, citrate must be transported to the cytosol (only if the citrate concentration is high) by a TCA transporter on the inner mitochondrial membrane; the citrate then allosterically inhibits PFK-1
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what reaction is catalyzed by PFK-1?
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phosphorylation of F6P to F1,6BP
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what reaction is catalyzed by PFK-2?
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when PFK-2 is unphosphorylated, it catalyzes the phosphorylation of F6P to F2,6BP
when PFK-2 is phosphorylated, it catalyzes the dephosphorylation of F2,6BP to F6P |
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explain the phosphatase activity of PFK-2
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when phosphorylated by PKA, PFK-2 acts as a phosphatase (removing phosphate from F2,6BP)
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explain the kinase activity of PFK-2
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when dephosphorylated, PFK-2 acts as a kinase (adding a phosphate to F6P, producing F2,6BP)
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what is the most potent allosteric activator of PFK-1?
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F2,6BP
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what are the allosteric activators of pyruvate kinase? what are the allosteric inhibitors?
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activators: F1,6BP
inhibitors: ATP, ACoA, Alanine |
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what is the enzymatic inhibition of pyruvate kinase (PK)?
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phosphorylation by PKA
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by what means is PKA regulated?
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glucagon binds to its GPCR
GPCR activates adenylate cyclase adenylate cyclase converts ATP to cAMP cAMP removes the regulatory subunits from PKA, making it active the process is inhibited when insulin binds its receptor, activating phosphodiesterase, which cleaves cAMP |
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what is the Kori cycle?
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glucose(m) -> pyruvate(m) -> lactate(m) ->lactate(h) -> pyruvate(h) -> glucose(h)
m=muscular; h=hepatic |
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by what enzymes is alcohol metabolized to acetate?
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ADH (cytosolic) converts EtOH to acetaldehyde
AcDH (mitochondrial) converts acetaldehyde to acetate both steps generate NADH |
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what is ADH?
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alcohol dehydrogenase
a cytosolic enzyme which converts ethanol to acetaldehyde, generating NADH |
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what is AcDH?
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acetaldehyde dehydrogenase
mitochondrial enzyme which converts acetaldehyde to acetate, generating NADH (important in the process of alcohol metabolism) |
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what determines the capacity to metabolize ethanol?
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the ability to shuttle NADH into the mitochondria
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why is less energy produced via glycolysis during ethanol metabolism?
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reduced oxidation of NADH impairs NAD+ levels and thereby reduces glycolytic flux at glyceraldehyde-3-phosphate dehydrogenase reaction
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why is gluconeogenesis inhibited during ethanol metabolism?
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increased NADH increases pyruvate conversion to lactate via lactate dehydrogenase (inhibits pyruvate conversion to glucose)
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where does ethanol metabolism occur?
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in the liver
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into what is acetate (from ethanol metabolism) converted?
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converted to acetyl-CoA, which would usually be oxidized in the TCA cycle, however NADH is maxed out, so acetyl-CoA is diverted to fat, leading to fatty liver
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why does ethanol metabolism drive triglyceride synthesis?
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acetyl-CoA can't be used via TCA cycle (fatty acids)
inhibition of glycerol-3-phosphate DH leads to increased glycerol-3-phosphate (backbone for triglycerides) combining the two in the liver leads to production of triglycerides |
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what leads to the acute toxic effects (hangover) from alcohol metabolism?
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acetaldehyde forms adducts with proteins and nucleic acids
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what effect does ethanol have on the CNS?
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inserts into membranes, altering action potentials, depressing function of the CNS
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what is cirrhosis? how does ethanol cause this?
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death of hepatocytes (liver becomes hard)
excess fat buildup in liver causes hepatocyte death |
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what is lactose?
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dissacharide of glucose and galactose
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what is maltose?
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dissacharide of glucose
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what is sucrose?
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dissacharide of glucose and fructose
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where is fructose primarily metabolized?
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liver
kidney small intestine |
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by what is fructose phosphorylated?
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in liver, fructokinase converts fructose to fructose-1-phosphate
in other tissues, hexokinase converts fructose to fructose-6-phosphate |
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what is the typical origin of a disorder in fructose metabolism?
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liver, because the liver sees most of the fructose that enters the body
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what is aldolase B?
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fructose-1-phosphate aldolase
cytosolic enzyme which hydrolyzes fructose-1-phosphate into glyceraldehyde and DHAP |
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what are the three disorders of fructose metabolism?
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essential fructosuria (fructokinase in liver)
hereditary fructose intolerance (fructose-1-P aldolase of liver, kidney cortex, and small intestine) F1,6BPase deficiency |
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essential fructosuria
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deficiency of fructokinase in the liver
autosomal-recessive inheritance asymptomatic with hyperfructosemia and fructosuria |
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why is essential fructosuria asymptomatic?
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deficiency of fructokinase
asymptomatic because fructose is not trapped within the cells |
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hereditary fructose intolerance
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fructose-1-phosphate aldolase deficiency
autosomal recessive inheritance treated by eliminating dietary fructose intake |
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what are the symptoms of hereditary fructose intolerance?
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severe hypoglycemia
vomiting on fructose intake prolonged intake in infants leads to poor feeding, vomiting, hepatomegaly, jaundice, proximal renal tubular syndrome failure to restrict fructose leads to liver failure and death |
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what is the treatment for hereditary fructose intolerance?
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restrict fructose, sucrose, and sorbitol intake (disorder becomes asymptomatic)
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what is sorbitol?
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sugar alcohol that is converted to fructose by succinate dehydrogenase
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why is hereditary fructose intolerance more of a problem than essential fructosuria?
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energy is trapped in liver cells as F1P; nothing can be done with it, so it builds up and eventually kills the cells
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F1,6BPase deficiency
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autosomal recessive inheritance
severe impairment of gluconeogenesis lethal in newborn if fructose isn't restricted past childhood, patients develop normally |
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what are the symptoms of F1,6BPase deficiency?
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episodic hyperventilation due to acidosis
hypoglycemia apnea ketosis lactic acidosis |
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what is GALK?
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galactokinase
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what is GALE?
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UDP-galactose epimerase
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what is GALT?
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UDP-glucose:galactose-1-P uridylyltransferase
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where does most galactose metabolism take place?
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in liver
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what are the three inherited disorders of galactose metabolism?
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classic galactosemia due to loss of GALT**
galactosemia due to loss of GALK** epimerase deficiency **lactose intolerant, can lead to blindness and fatal liver damage |
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what are the symptoms of GALT deficiency?
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aka classic galactosemia due to loss of uridylyltransferase
poor feeding, weight loss, vomiting, diarrhea, lethargy, jaundice, hepatomegaly in first weeks after birth also bleeding disorders and renal tubular disease |
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why are bleeding disorders common in GALT deficiency?
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liver dysfunction disrupts clotting factor production
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how is GALT deficiency treated?
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restriction of galactose intake
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what are the forms of epimerase deficiency?
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major defect is in erythrocyte enzyme (GALE) and is benign
rare defect is in liver enzyme (GALE) and is similar to GALT deficiency |
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what is the consistent finding in patients with GALK deficiency?
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cataracts (galactose in blood leads to buildup of galactitol in lens of eye)
most symptoms resolve upon galactose restriction not as severe as GALT deficiency |
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what is the most important defect in galactose metabolism, clinically?
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classic galactosemia due to deficiency of uridylyltransferase
(GALT deficiency) |
