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298 Cards in this Set
- Front
- Back
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Define Enzymes
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Enzymes are protein catalysts that increase the rate of reactions, but are not changed in the process.
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Six classes of enzymes
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Oxidoreductase
Transferase Hydrolase Lyase Isomerase Ligase |
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Fn: Oxidoreductase
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Oxidoreductase – catalyzes redox reactions e.g. lactate dehydrogenase
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Fn: Hydrolase
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Hydrolase – cleavage of bonds by addition of water e.g. urease
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Fn: Ligase
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Ligase – formation of new bonds between C and O,S or N
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Fn: Transferase
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Transferase – transfers C,N or P containing groups e.g. serine hydroxymethyl transferase
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Fn: Isomerase
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Isomerase – racemisation of optical or geometric isomers e.g. methylmalonyl CoA mutase
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Fn: Lyase
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Lyase – cleavage of C-C C-S or N-C bonds e.g.pyruvate decarboxylase
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How many S -> P per second?
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Each enzyme can transform 100 – 1000 S molecules into P every second.
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What does turnover number mean?
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The number of S → P transformations per E molecule per second is called the turnover number.
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Holoenzyme
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An enzyme with its cofactor is called a holoenzyme
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Apoenzyme
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An enzyme without its cofactor is called an apoenzyme
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Composition of cofactors?
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Non-protein
Organic molecules Metal Ions |
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________________ allows substrates and products to be at different concentrations in different parts of the cell
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compartmentalization
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Effect of enzymes on activation energy?
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Lower energy of activation.
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Which type of chemical conformation lowers the energy of activation the most?
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Chair conformation
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What is the only factor changed by a catalyst?
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The rate of rxn.
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Two models of enzyme binding?
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Lock and Key
Induced Fit |
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At what point is Vmax reached?
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When the enzyme is saturated.
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What type of enzymes show sigmoidal profiles?
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Allosteric enzymes
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Increase T, what happens to V?
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Increase V
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What happens to enzymes at high temp?
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Enzymes are denatured at high temperatures
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Michaelis-Menten Equation
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Michaelis-Menten Equation
Vo = Vmax[S]/(KM + [S]) Vo = initial velocity KM = Michaelis constant = (k-1 +k2)/k1 |
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When is KM numerically equal to [S]?
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KM is numerically equal to [S] at ½ the maximal velocity
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T or F: KM does not vary with enzyme concentration
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True
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If KM is small the affinity of E for S is ____.
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High
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A ___ [S] is able to half-saturate the enzyme
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Low
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If KM is _____, the affinity is small
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Large.
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Rate is ________________ to [E] at all S concentrations
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Directly proportional
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This is first order kinetics
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If [S] << KM the velocity will be proportional to [S]
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This is zero order kinetics
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If [S]>> KM the velocity will be Vmax and independent of [S]
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___________ inhibition may be competitive, noncompetitive or uncompetitive.
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Reversible inhibition may be competitive, noncompetitive or uncompetitive.
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What does competitive inhibition look like on a graph?
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Crosses at the Y axis.
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What statin drug is a good example of a competitive inhibitor? What do they inhibit?
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Lovastatin
HMG-CoA Reductase Inhibitors |
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Competitive Inhibitor vs Noncompetitive inhibitor...binding site.
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Competitive competes for the smae binding site whereas the inhibitor and substrate bind at different sites in noncompetitive inhibition.
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Non-competitive inhibition: Effect on Vmax
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Vmax decreases
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Non-competitive inhibition: Effect on Km
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Unchanged
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Non-competitive inhibition: what does the graph look like?
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The lines do NOT intersect. The two line have the same Km (x intercept), but have different Vmax (y-intercept) values.
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Effects of uncompetitive inhibition on Vmax, Km & Lineweaver-Burke plot.
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Vmax => lowered.
Km => stimulates formation of ES and increases binding of substrate to enzyme so Km is reduced. Plot => parallel lines. |
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What is an allosteric site?
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allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the protein's allosteric site (that is, a site other than the protein's active site).
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Enzymes that are involved with Glycogen syn. are _________ by phosphorylation.
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Deactivated
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Enzymes that are involved with Glycogen degradation are _______ by phosphorylation.
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Activated
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The presence and concentration of this may be used to diagnose heart disease.
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Creatine Kinase
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This Creatine Kinase isoenzyme is only produced by the myocardium, plasma levels peaking around 24 h after infarction.
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CK2
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A tightly bound coenzyme that doesn’t dissociate is called a _______________.
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Prosthetic group
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Cmpds that have the same chemical formula but have different structures are called?
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Isomers
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Isomers that differ in configuration around only one specific C atom are called?
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epimers
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The majority of sugars foudn in humans are L-sugars...T or F?
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False. D-sugars are the most abundant
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Principal sites of carbohydrate digestion (2).
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Mouth & Intestinal lumen
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What enzymes (2) are needed fot degredation of most dietary carbs?
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disaccharidases and endoglycosidases
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Where does digestion of carbs begin? What enzyme is used?
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Digestion begins in the mouth by salivary amylase.
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Fn. of salivary amylase?
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Randomly breaks the alpha(1=>4)bonds.
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Where do the final digestive processes take place?
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At the mucosal lining of the upper jejunum, declinnig as they proceed down the small intestine.
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______ and _______ absorb the bulk of the dietary sugars.
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duodenum & upper jejunum
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Insulin is not req'd for the uptake of glucose by intestinal cells...T or F?
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True
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What type of bonds link the monosacharides in disaccharides, oligosaccharides and polysaccharides?
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glycosidic bonds
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When is a sugar considered a reducing sugar?
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If the oxygen on the anomeric carbon is not attached to any other structure, the sugar is considered a reducing sugar.
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Salivary a-amylase acts on dietary starch producing ________.
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oligosaccharides
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Undigested carbohydrate, due to a carb degradation deficiency, passes into the large intestine. This will cause?
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Osmotic diarrhea.
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Lactose intolerance is caused by a deficiency in what enzyme?
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Lactase
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Catabolism
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Catabolism –degradation => cell constituents & nutrients are broken down
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Anabolism
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Anabolism –biosynthesis => biomolecules are synthesized from simpler molecules
Metabolic pathways are a series of connected |
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T or F: Catabolism consumes ATP and other high energy phosphates.
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False: Catabolism releases ATP and other high energy phosphates.
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The first irreversible step.
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The Committed Step
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The committed step in glycolysis
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PFK-1
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The committed step in F.A. Syn.
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Acteyl CoA Carboxylase
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The rates of synthesis and degradation of many regulatory enzymes are altered by ________.
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The rates of synthesis and degradation of many regulatory enzymes are altered by HORMONES.
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What type of cascade controls the effect of hormones on enzyme presence or lack thereof?
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Signal Transduction cascades
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Signalling pathways are regulated by _______.
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Feedback pathways.
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2 classes of hormones are?
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Group I - Hormones that bind to intracellular receptors.
Group II - Hormones that bind to cell surface receptors. |
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Steroid hormones: What type of signal molecules are estrogens?
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Estrogens: nonpolar cholesterol-derived signalling molecules
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Steroid receptors have Receptors have two highly conserved domains. What are they?
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A DNA-binding domain (with Zinc finger motifs) and
A ligand-binding domain |
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At what site do hormone bound receptors bind to DNA?
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The Hormone bound receptors bind to DNA at specific sequences called Hormone Responsive Elements (HRE), e.g. Estrogen at ERE.
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Structure of G-protein?
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heterotrimeric - consisting of a, b and gamma subunits.
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What happens to a G-Protein when GTP is bound?
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The α subunit simultaneously dissociates from the βγ dimer
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Ligand binds to Receptor => Activated Receptor => Activates G protein => Activates (a.)_______ => Leading to increased (b.)______ and => Activated effectors.
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(a.) Adenylate Cyclase
(b.) cAMP |
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Draw glycolysis/gluconeogenesis & include the enzymes.
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DRAWING.
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Three classic examples of RTKs.
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1. Insulin
2. PDGF (platelet-derived GF) 3. EGF (epidermal GF) |
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EGF signalling pathway
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EGF binds to its receptor => leads to cross-phosphorylation of the receptor => phosphorylated receptor binds Grb-2 => binds Sos => Sos stimulates the exchange of GTP for GDP in Ras => Activated Ras binds to and stimulates protein kinases.
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Fn of GLUT1 and GLUT3
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Responsible for basal glucose uptake.
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Where can you find GLUT2?
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GLUT2 - present in liver and pancreatic β cells,
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GLUT2 has a characteristic Km for glucose...high or low?
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Very high KM value for glucose
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GLUT 4 - FN.
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GLUT4 - transports glucose into muscle and fat cells.
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Effect of increased insulin on GLUT4?
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insulin => signals the fed state, => rapid increase in the number of GLUT4 transporters in the plasma membrane. Hence, insulin promotes the uptake of glucose by muscle and fat.
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Where would you find GLUT5?
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small intestine
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Fn - GLUT5?
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functions primarily as a fructose transporter.
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Under aerobic conditions, the dominant product in most tissues is ______ and the pathway is known as ______ glycolysis.
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Pyruvate
Aerobic |
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During prolonged vigorous exercise, the dominant glycolytic product in many tissues is _____ and the process is known as ______ glycolysis.
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Lactate
Anaerobic |
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What intermediate is req'd by hexokinase to catalyze Glucose --> G6P?
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Mg2+
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The fate of pyruvate depends on what?
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The fate of pyruvate depends on the oxidation state of the cell.
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Under what conditions is ethanol a product of pyruvate?
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In yeast and other microorganisms
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What enzyme is responsible for pyruvate --> ethanol?
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pyruvate decarboxylase and alcohol dehydrogenase
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Under what conditions does pyruvate get converted to lactate?
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Anaeorbic (low O2) conditions
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Glycolysis under anaerobic conditions. How is this sustained?
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The regeneration of NAD+ in the reduction of pyruvate to lactate or ethanol sustains the continued operation of glycolysis under anaerobic conditions .
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Pyruvate => Lactate. Enzyme?
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Lactate Dehydrogenase
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In Glycolysis, the irreversible reactions (3) are catalyzed by?
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Hexokinase,
Phosphofructokinase (PFK1) Pyruvate kinase |
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Effect of ATP on PFK-1?
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Inhibitory
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Effect of pH on PFK-1?
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Decreased pH = inhibitory
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Effect of citrate on PFK-1?
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Inhibits by acting to increase effects of ATP.
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Fructose 2,6-bisphosphate is an allosteric _______ that shifts the conformational equilibrium of PFK (tetrameric enzyme) from a __ state to an __ state.
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Activator
T R |
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What is the bifunctional enzyme?
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PFK-2/FBPase-2
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When glucose is low, phosphorylation (a.)________ FBPase2 and (b.)__________ PFK2, & (c.)________ the level of F-2,6-BP.
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(a.) activates
(b.) inhibits (c.) lowers |
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When glucose is scarce,
Hormone glucagon is produced. Glucagon stimulates production of _______. |
cAMP
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When glucose is scarce
Hormone glucagon is produced. Glucagon stimulates production of cAMP. cAMP activates ____________. |
cAMP activates protein kinase A (PKA)
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When glucose is scarce
Hormone glucagon is produced. Glucagon stimulates production of cAMP. cAMP activates PKA, and PKA ___________ PFK2/FBPase2. |
PKA phosphorylates PFK2/FBPase2
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When glucose is abundant, the bifunctional enzyme is dephosphorylated. This ______ PFK2 and ______ FBPase2
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activates PFK2
inhibits FBPase2 |
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PFK is activated by _____ & ______. While it is inhibited by ______ & _____.
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Activated by: F-2,6-BP & AMP
Inhibited by: ATP & Citrate |
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In what form is glucose stored?
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Glycogen
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What inhibits Hexokinase?
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Glucose-6-Phosphate
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Type IV isozyme of hexokinase is...
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Glucokinase
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Glucokinase is inhibited by?
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Nothing, thus allowing glucose accumulation in the liver.
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Fn. & location of:
Hexokinases vs Glucokinases? |
Hexokinases: Peripheral use of glucose; All tissues
Glucokinases: Glycogen stores & release of insulin; Liver & Pancreas |
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Both ____ & _____ inhibit Pyruvate kinase.
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ATP & Alanine
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What is the importance of 2,3-BPG?
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an important regulator of hemoglobin affinity for oxygen.
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How is 2,3-BPG synthesized, from what substrate and uses what enzyme?
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1,3-BPG --Bisphosphoglycerate mutase--> 2,3-BPG.
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2,3-BPG ==> 3-phosphoglycerate via what enzyme?
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2,3-Bisphosphoglycerate phosphatase
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2,3-BPG ==> 3-phosphoglycerate via what enzyme?
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2,3-Bisphosphoglycerate phosphatase
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Patients with glycolytic defects present with _________?
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Patients present with a congenital nonspherocytic hemolytic anemia of variable severity.
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________ deficiency and _______ deficiency are localized to the RBC with no apparent metabolic abnormality in other cells.
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Pyruvate kinase (PK) deficiency and hexokinase deficiency are localized to the RBC with no apparent metabolic abnormality in other cells.
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_____ deficiency most common cause for hemolytic anemia after G6PD deficiency.
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PK
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In what fashion is PK deficiency inherited?
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PK deficiency is inherited in an autosomal recessive pattern.
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During short term starvation, which tissue is performing gluconeogenesis?
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Liver
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During long term starvation, which tissue is performing gluconeogenesis?
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Kidney
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Gluconeogenesis is the reverse of glycolysis, except for three steps. What are they?
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The three kinase steps in glycolysis (Hexokinase/Glucokinase, PFK & pyruvate kinase).
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Gluconeogenesis takes place in the ________.
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Unlike glycolysis, part of gluconeogenesis takes place in the mitochondrion.
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Under fasting conditions the body can manufacture glucose from (a.)_________, (b.)________, (c.)__________ or (d.)____________.
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(a.)lactate,
(b.)pyruvate, (c.)glycerol or (d.)α-keto acids |
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Glycerol ==> DHAP
(a.) Where does Glycerol come from? (b.) What enzyme catalyzes this rxn? |
(a.) Hydrolysis of TAG in Adipose Tissue.
(b.)Glycerol Kinase phosphorylates => DHAP. |
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Gluconeogenesis: Most important source under non-fasting conditions?
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Lactate
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Lactate can be released by RBCs that lack what?
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mitochondria
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Lactate ==> Pyruvate, via what enzyme? In what tissues?
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Lactate Dehydrogenase
Liver NOTE: Lactate ==> Pyruvate is referred to as the Cori cycle. |
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Gluconeogenesis: Most important source under fasting conditions?
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Amino Acids
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Why can't Acetyl CoA enter gluconeogenesis?
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AcetylCoA and amino acids that produce it (are ketogenic), cannot enter gluconeogenesis because the decarboxylation of pyruvate is irreversible.
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Classic e.g. of an amino acid that can be used in gluconeogenesis?
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Alanine
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Gluconeogenesis: Carboxylation of Pyruvate ==> OAA via what enzyme?
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Pyruvate Carboxylase
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OAA => PEP; what enzyme?
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PEP Carboxykinase
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What effect does ethanol metabolism have on gluconeogenesis?
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Inhibitory
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Alcoholics, if fallen asleep in the cold, can die because of what enzyme?
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Malate Dehydrogenase.
The NADH also favors reduction of oxaloacetate to malate in the reaction catalyzed by malate dehydrogenase, making less oxaloacetate available for gluconeogenesis. The resulting hypoglycemia can affect the part of the brain concerned with temperature regulation and the body temperature can fall by as much as 2 oC. |
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Gluconeogenesis: Dephosphorylation of fructose 1,6-bisphosphate by what enzyme?
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fructose-1,6-bisphosphatase
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F-1,6-bisphosphatase is inhibited by ___ and promoted by ___.
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F-1,6-bisphosphatase is inhibited by AMP and promoted by ATP
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fructose-1,6-bisphosphatase (gluconeogenic enzyme) is inhibited by what?
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Fructose-2,6-Bisphosphate.
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Gluconeogenesis: _________ bypasses the hexokinase reaction.
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Glucose-6-phosphatase
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G-6-Phosphatase is cannot be found in what type of tissue?
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Muscle
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NOTE
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Gluconeogenesis: memorize slide #29.
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Location of TCA?
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Mitochondria
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TCA: Aerobic, anaerobic or both?
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Aerobic only.
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Pyruvate ==> Acetyl CoA by the pyruvate decarboxylase complex. Whta are the three enzymes involved in this process?
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E1: Pyruvate decarboxylase/dehydrogenase
E2: Dihydrolipoyl transacetylase E3: dihydrolipoyl dehydrogenase |
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What are the coenzymes req'd by each of the three enzymes in the pyruvate dehydrogenase complex?
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E1: TPP
E2: Lipoic acid & CoA E3: FAD & NAD+ |
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What two regulatory enzymes are included in the pyruvate dehydrogenase complex?
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Complex also contains regulatory protein kinase and phosphoprotein phosphatase
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Congential lactic acidosis is caused by what deficiency?
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Deficiency in PDH, therefore cannot process Pyruvate ==> Acetyl CoA
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Arsenic inhibits what enzyme?
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Pyruvate Dehydrogenase
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Acteyl CoA + OAA ==> Citrate.
Enzyme? |
Citrate synthase
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Citrate inhibits what glycolytic enzyme?
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PFK
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What cycle does Citrate activate?
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F.A. Synthesis.
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Citrate ==> Isocitrate
Enzyme. |
Aconitase
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Isocitrae ==> a-ketogluterate
Enzyme? |
Isocitrate dehydrogenase
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What is the RLS of the TCA?
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Isocitrae ==> a-ketogluterate
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α-ketoglutarate ==> succinyl CoA.
Enzyme? |
α-ketoglutarate dehydrogenase complex
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Succinate thiokinase (Succinyl CoA synthetase) catalyzes what TCA step?
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Succinyl CoA ==> Succinate
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The 6th step of the TCA, succinate ==> fumarate, by succinate dehydrogenase requires what prosthetic group?
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FAD.
FAD is reduced to FADH2 |
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Fumarate ==> Malate.
Enzyme? |
Fumarase
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Malate ==> OAA
Enzyme? Prosthetic group? |
Malate Dehydrogenase
NAD+ is reduced to NADH. |
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TCA: __ acetyl group enters, __ CO2 molecules leave, so no net carbon consumption
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1 acetyl group enters, 2 CO2 molecules leave, so no net carbon consumption
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TCA:
Each NADH yields __ ATP Each FADH2 yields __ ATP |
Each NADH yields 3 ATP
Each FADH2 yields 2 ATP |
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TCA produces __ GTP directly
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One.
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Roughly __ ATP from 1 glucose molecule due to TCA.
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24
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TCA: These three enzymes are affected allosterically most often.
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Citrate synthase
Isocitrate dehydrogenase α-ketoglutarate dehydrogenase complex |
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Energy Metabolism:
Glycolysis (Net) _ NADH _ ATP Pyruvate Dehydrogenase (Two pyruvates per glucose) _ NADH TCA (two AcetylCoA per glucose) _ NADH _ FADH2 _ ATP (as GTP) |
Glycolysis (Net)
2NADH 2ATP Pyruvate Dehydrogenase (Two pyruvates per glucose) 2NADH TCA (two AcetylCoA per glucose) 6NADH 2FADH2 2ATP (as GTP) |
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Glycolysis (Net)
_ NADH _ ATP |
Glycolysis (Net)
2NADH 2ATP |
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Pyruvate Dehydrogenase (Two pyruvates per glucose)
_ NADH |
Pyruvate Dehydrogenase (Two pyruvates per glucose)
2 NADH |
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TCA (two AcetylCoA per glucose)
_ NADH _ FADH2 _ ATP (as GTP) |
TCA (two AcetylCoA per glucose)
6NADH 2FADH2 2ATP (as GTP) |
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Total approximately __ ATP per glucose
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Total approximately 38 ATP per glucose
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Oxidative Phosphorylation (ETC) occurs in what location?
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Inner mitochondrial membrane
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The ultimate product of the ETC is what?
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Oxygen
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ETC: Name of complex I?
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NADH Dehydrogenase
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These compnents of complex I aid in the transport of H+ and e- to the next carrier, CoQ.
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Fe-S centers.
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CoQ Complex in ETC can accept H+ and e- from three sources. What are they?
|
Can accept H+ and electrons from FMNH2 (in complex I) and FADH2 (in complex II) and also from acylCoA dehydrogenase (in FA oxidation)
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ETC: Name complex II
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Succinate Dehydrogenase
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ETC: What is unique about the protons in complex II?
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No protons are pumped out in this step.
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ETC: Complex III -
Sometimes called _________. |
coenzyme Q : cytochrome C oxidoreductase
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Complex IV
Cytochrome C oxidase...contains two centers. What are they and what do they contain? |
a & a3 which contain Fe and Cu
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Inhibitors of ETC: What are they are what complexe(s) do they inhibit?
|
Amytal (a barbiturate drug) and rotenone (an insecticide) block the transfer of electrons from NADH to CoQ in complex I
Antimycin A (streptomyces antibiotic) blocks electron flow from b to c1 in complex III Carbon monoxide blocks the reduced form of complex IV, cyanide (CN-)and azide (N3-) block the oxidized form. |
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Defects of OxPhos will cause what type of inherited diseases?
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Diseases with mt inheritance, ex. LHON.
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Most of the glucose residues in glycogen are linked by ___________ bonds.
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Most of the glucose residues are linked by α-1,4-glycosidic bonds.
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Glycogen branches are located at about every ____ residue by _____________ bonds.
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Branches at about every 8-14 residue by α -1,6-glycosidic bonds
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From which end are glucose units mobilized from glycogen?
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the nonreducing ends
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The two main functions of branching in glycogen.
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1. Branching increases the rate of glycogen synthesis and degradation.
2. Increases the solubility of glycogen. |
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Glycogen has two major storage sites
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liver and skeletal muscle.
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In what form is glycogen present in the cytosol?
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In granules
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What are the three steps in glycogen degradation?
|
Glycogen degradation consists of three steps:
1. the release of glucose 1-phosphate from glycogen, 2. the remodeling of the glycogen substrate to permit further degradation, and 3. the conversion of glucose 1-phosphate into glucose 6-phosphate for further metabolism. |
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Glycogen synthesis: Adds glucose to what end?
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Nonreducing ends
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What type of glucose is req'd. for glycogen synthesis?
|
UDP-Glucose (activated glucose)
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Glycogenolysis: Fn. of Glycogen phosphorylase?
|
Cleaves (from the nonreducing end) by the addition of orthophosphate (Pi) to yield glucose 1-phosphate.
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Glycogen phyophorylase automatically stops clevage of glucose units at what point?
|
When there are only 4 residues left until a branch point.
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Because glycogen phosphorylase cannot be used to cleave glycogen when down to four glucose units from a branch point, what key enzyme(s) aid in this process?
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transferase and
α-1,6-glucosidase |
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Type I Glycogen Storage Disease. What is the defective enzyme?
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Glucose 6-phosphatase
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Type II Storage Disease, what organs are affected?
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All organs
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Type I storage disease, what organs are affected
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Liver and Kidney
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What Type of storage disease is Pompe's?
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Type II
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What type of storage disease is VonGierke disease?
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Type I
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What enzyme is affected in Type II storage disease?
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α-1,4-Glucosidase (lysosomal) =>Acid Maltase
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Massive enlargement of the liver. Failure to thrive. Severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia. Normal Glycogen structure. What storage disease am I?
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Type I - VonGierke
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Cardio respiratory failure causes death, usually before age 2; Characterized by accumulation of glycogen in heart muscle. What storage disease am I?
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Type II - Pompe's
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Type III - Cori disease. What organs are affected?
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Muscle and liver
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Type III - Cori disease. What enzyme is affected?
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Amylo-1,6-glucosidase (debranching enzyme)
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This GSD presents Like type I, but milder course.
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Type III - Cori & VI - Hers disease
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GSD Type IV - Andersen disease. What enzyme is defective?
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Branching enzyme (a-1,4 ==> a-1,6).
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Progressive cirrhosis of the liver. Liver failure causes death, usually before age 2. Progressive cirrhosis of the liver. What GSD am I?
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GSD Type IV - Andersen disease.
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GSD Type IV - Andersen disease. What organs are affected?
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Liver and Spleen
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Phosphorylase is the defective enzyme in this type of GSD?
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V - McArdle disease & VI - Hers disease.
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The only affected organ is the muscle...what two GSDs does this correspond to?
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Type V (McArdle) & VII
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Limited ability to perform strenuous exercise because of painful muscle cramps. Otherwise patient is normal and well developed. What GSD?
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Type V (McArdle)
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GSD Type VII - presents like Type V, however, this enzyme is defective?
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PFK
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Structure of glycogen in Type I GSD.
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Normal Structure, increased amount of glycogen.
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______ is the most widely used monosaccharide
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glucose is the most widely used monosaccharide
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Hexokinase vs Glucokinase. Present in what organ?
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Hexokinase = Muscle
Glucokinase = Liver |
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Lack of Fructo kinase (which is normally present in the liver, pancreatic islets and kidney cortex), is indicative of what disease?
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Fructosuria
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Hereditary fructose intolerance is potentially lethal. Lack of this enzyme ________, leads to an accumulation of Fructose-1- Phosphate.
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Aldolase B
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Unlike patients with fructosuria, patients with hereditary fructose intolerance present with the following symptoms?
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vomiting, poor feeding, jaundice, hepatomegaly, lactic acidosis, hyperuricemia, hemorrhage and eventually hepatic failure and death
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Acute loading of liver with fructose => sequestration of Pi in F 1-P => Decreased ATP synthesis => decreased inhibition of purine synthesis => Increased uric acid formation. What disease?
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Hyperuricemia
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Galactose is converted into glucose 6-phosphate in four steps. What are they?
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1. Galactose is phosphorylated by galactokinase => galactose-1-phosphate
2. transfer of UDP from UDP-glucose, catalyzed by galactose-1-phosphate uridyl transferase => UDP-galactose and G1P 3. UDP-galactose epimerized to UDP-glucose by UDP-galactose-4 epimerase. 4. The UDP portion is exchanged for phosphate generating glucose-1-phosphate which then is converted to G6P by phosphoglucose mutase. |
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Required for biosynthesis of Lactose, glycoproteins, Glycolipids and Glycosaminoglycans
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UDP-Galactose
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Classic Galactosemia is a major symptom of two enzyme defects.
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galactose-1-phosphate uridyl transferase or
galactokinase |
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**Galactosemia diagnostic triad.
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mental retardation, cirrhosis, cataract
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What are the two enzymes required for the conversion of glucose to fructose?
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Aldose reductase D - glucose reduced to sorbitol & Sorbitol dehydrogenase - sorbitol is oxidized to fructose.
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The sorbitol pathway is useful in seminal vesicles as ______ is the major source of energy for sperm.
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fructose
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Mannose ==> Mannose-6-Phosphate. What enzyme?
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Hexokinase
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Mannose ==> Mannose-6-P ==> Fructose-6-P. vs
Mannose ==> Mannose-6-P ==> F6P==> Glucose-6-Phosphate. What pathways use these products? |
F6P => Glycolysis
G6P => Gluconeogenesis |
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Phosphomannose isomerase, catalyzes what rxn?
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Mannose-6-P ==> F6P
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How many glucose are req'd to syn Lactose?
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two
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Glut __ is responsible for Glucose passing across the Golgi apparatus membrane into the Golgi apparatus lumen.
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GLUT 1
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Lactose synthesis after birth: galactosyltransferase associates with a-lactalbumin and changes its specificity in mammary glands to _____________.
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lactose synthase
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What are the two primary functions of the Pentose Phosphate Pathway (HMP Shunt)?
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The primary functions of this pathway are:
1. generate reducing equivalents, in the form of NADPH and, 2. provide ribose-5-phosphate (R5P). |
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Pentose Phosphate Pathways & the corresponding tissues include (4):
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- Steroid Synthesis (adrenal, Testis, Ovary)
- F.A. Synthesis (Liver, Adipose, Mammary) - Cholesterol Synthesis (Liver) - Maintenance of reduced glutathione (RBC) |
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HMP: Oxidative vs Non-oxidative steps.
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Oxidative steps generate NADPH and are irreversible whereas, Non-oxidative are reversible, syntheize R5P and convert 5 carbon sugars into 6 & 3-C sugars.
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NADPH vs NADH
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NADPH - reductive biosyntheses
NADH - generation of ATP. |
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NADPH uses the reduction of _____. This is part of the ROS family.
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H2O2
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Define ROS.
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ROS has one or more unpaired electrons in their valence shell.
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Fn. of an antioxidant?
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a molecule capable of slowing or preventing the oxidation of other molecules, thus preventing the potentially harmful effects on cells.
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Antioxidant: an oxidizing or reducing agent? Give an example.
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Reducing agent, e.g. Thiol & polyphenols.
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Fn of Glutathione.
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Degredation of hydroperoxides.
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2 GSH + ROOH ==> GSSG + ROH + H2O
This rxn is catalyzed by what enzyme? |
Glutathione Peroxidase
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Glutathione Peroxidase uses the trace element __________ as functional group.
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selenium
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GSSG + NADPH + H+ ==> 2 GSH + NADP+
What enzyme catalyst? |
Glutathione Reductase
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Genetic deficiency of Glucose-6-P Dehydrogenase can lead to ______________, due to inadequate _________ within red blood cells.
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Genetic deficiency of Glucose-6-P Dehydrogenase can lead to hemolytic anemia, due to inadequate [NADPH] within red blood cells.
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Due to its high concentration and its central role in maintaining the cell's redox state, ____________ is one of the most important cellular antioxidants
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Glutathione
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Cytochrome P450 monooxygenase system: Mitochondrial vs microsomal
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Mt: Endogenous synthesis of cholesterol ,steroid hormones and bile salts, vitamin D
Microsomal: detoxification of foreign substances (xenobiotic compounds) by oxidative metabolism, e.g. metabolize ibuprofen, caffiene. |
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The active site of cytochrome P450 contains a ________ center
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The active site of cytochrome P450 contains a heme iron center.
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NOTE - The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction:
RH + O2 + 2H+ + 2e– → ROH + H2O |
NOTE - The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction:
RH + O2 + 2H+ + 2e– → ROH + H2O |
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Negative Impact of CYP?
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Creates harmful carcinogens from harmless carcinogens.
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Phagocytosis utilizes ______ to perform a variety of functions. List the 4 stimulatory effects of Phagocytosis by WBC?
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1. burst in oxygen consumption,
2. glycogenolysis, 3. Increase glucose oxidation via the HMP shunt, and 4. production of ROS |
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Deficiency of NADPH oxidase causes?
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Deficiency of NADPH oxidase ==> chronic granulomatous disease
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Role of superoxide dismutase?
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Superoxide ==> H2O2
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1. NOS catalyzes what reaction?
2. What is enzyme cofactors are required? 3. What other cofactors are req'd? |
1. Arginine ==> NO + Citrulline
2. NADPH, CO2 3. FMN, FAD, Heme and Tetrahydrobiopterin are coenzymes |
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There are three types of NOS, which are constitutive and which inducibe?
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nNOS (neuronal) & eNOS (endothelial) are constitutive, while iNOS is inducible.
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Effects of NO syntesis on the following:
-vascular smooth muscle tissue -microbes -NOTE: NO can also be used as a NT. |
-potential vasodilator & decrease platelet aggregation which can occur in diabetes, athlersclerosis, and hypertension
-NO and its derivatives are microbicidal, limit microbial growth. |
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Characteristic causes of G6PD deficiency (4)?
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=>Antimalarial drugs (primaquine)
=>Infections -- e.g. viral hep, pneumonia =>Too many fava beans (favism) =>Neonatal jaundice (uncommon) |
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Under what condition are Heinz Bodies observed?
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During hemolysis RBC lacking G6PD are denatured and form precipitants, aka Heinz Bodies.
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Acute intravascular hemolysis marked by anemia, hemoglobinemia, and hemoglobinuria; begins 2 to 3 days following exposure to oxidants.
What disorder? |
G6PD Deficiency
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Long unbranched polysaccharides containing a repeating disaccharide unit.
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GAG
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What are the 2 components of the disaccharide unit in a GAG?
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One of two modified sugars (GalNAc or GlcNAc) & a uronic acid (ex. Glucuronate).
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Primary location of a GAG?
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On the surface of cells or in the extra cellular matrix (ECM).
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Hyaluronic acid,
Dermatan sulfate, Chondroitin sulfate, Heparin, Heparan sulfate, and Keratan sulfate These are all examples of ____. |
GAGs
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Which GAG is non sulfated & not covalently linked to proteins?
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Hyaluronic Acid
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In what tissue/location would Hyaluronic acid be found & why?
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Synovial fluid, vitreous humor, ECM of loose connective tissue; because it is a lubricant and shock absorber.
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This GAG is found in skin, blood vessels, heart valves.
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Dermatan Sulfate
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Where can Chondroitin 4- and 6-sulfates be found?
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Cartilage, tendon, ligament & aorta
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Chondroitin 4- and 6-sulfates form PG aggregates by assembling with what other GAG?
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Hyaluronic acid.
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Most abundant GAG
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Chondroitin 4- and 6-sulfates.
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______ only intracellular GAG => found in mast cells lining arteries in liver, lungs and skin
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Heparin
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Function of Heparin?
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Anticoagulant
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Location of Heparan sulfate?
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Heparan sulfate => basement membrane and cell surfaces
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This GAG has Galactose as a primary structural component & does NOT have uronic acid.
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Keratan sulfate.
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Location of Keratan sulfate.
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cornea, bone, & cartilage aggregated with Chondroitin sulfates.
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What does a PG look like?
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A brush
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GAGs linked to core proteins => _____________
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Proteoglycan (PG)
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PG - a ____________ linker is coupled to the protein core through an O-glycosidic bond to a Serine residue in the protein.
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Trisaccharide
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The protein cores of PGs are rich in ______ and _______ residues, which allows multiple GAG attachments.
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Serine and Threonine
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What are the three primary functions of PGs?
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1. Structural support to tissues,
2. Ability to withstand torsion and shock, and 3. Binding of proteins and enzymes to vascular walls. |
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Fructose 6 phosphate is the precursor to ______.
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GAGs
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Degradation of GAGs occurs in __________.
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Lysosomes.
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_____________________ result from defects in enzymes responsible for Degradation of GAGs.
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lysosomal storage diseases
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lysosomal storage diseases are termed what?
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MPS -- mucopolysaccharidoses
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All of the MPS are inherited in an __________ manner, except Hunters which is X-Linked.
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AR
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oligosaccharides covalently attached to proteins are
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glycoproteins
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Location and function of glycoproteins.
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Location: cell surfaces
Functions: -communication between cells, -maintaining cell structure and -self-recognition by the immune system. |
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Glycoproteins: carbohydrates linked to protein through two different linkages...
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N-glycosidic bonds
O-glycosidic bonds |
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N-linked glycoproteins all contain a common core of ____________ attached to the polypeptide.
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N-linked glycoproteins all contain a common core of carbohydrate attached to the polypeptide.
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How is a O-glycosidic bonded (what a.a)?
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to the hydroxyl of serine, threonine or hydroxylysine
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N-linked glycoprotein synthesis requires a lipid intermediate: __________________.
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N-linked glycoprotein synthesis requires a lipid intermediate: dolichol phosphate
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N-linked sugars: Carbohydrate core consists of ________, __________ and ________ residues attached to dolicholpyrophosphate; this is know as the lipid-linked oligosaccharide (LLO).
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glucose
mannose GlcNAc |
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|
Characterized by severe psychomotor retardation, skeletal abnormalities, coarse facial features, painful restricted joint movement, and early mortality
|
I-cell disease (Mucolipidoses II): High concentrations of lysosomal enzymes in plasma
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Degradation of glycoproteins within lysosomes occurs via what enzyme?
|
glycosidases
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Defects in the genes encoding specific glycosidases, => incomplete degradation and subsequent over-accumulation of partially degraded glycoproteins => leads to what type of diesases?
|
lysosomal storage diseases
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N-linked glycoproteins vs O-linked glycoproteins -- post-translationally or cotranslationally?
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N-linked glycoproteins => cotranslationally vs
O-linked glycoproteins => post-translationally |
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Glycoproteins: Where are the sugar groups processed?
|
Lumen of the ER
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How are N-glycosidic bonds formed (a.a.)?
|
Through the amide group of asparagine
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How are O-glycosidic bonds formed (a.a.)?
|
To the hydroxyl of serine, threonine or hydroxylysine
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Enzyme Defect in the following MPS:
Hurlers Scheie's |
α-L-iduronidase
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