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143 Cards in this Set
- Front
- Back
Where are the 3 main glycogen stores of the body? What is the caveat about muscle storage?
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Liver
Proximal tubule of the kidney Muscle Cannot be used to give rise to blood glucose. G6P cannot be dephosphoylated because of lack of G-6Pase. Instead, G6P is used for muscle contraction. |
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What is the reaction catalyzed by glycogen phosphorylase? When does it stop?
|
(Glycogen)n glu + Pi =
(Glycogen)n-1 glu + Glu 1-P It stops within 4 glycosyl units before the branch point (limit dextrin). |
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What does the debranching enzyme do to the 4 glycosyl unts not cleaved by glycogen phosphorylase?
|
Removes three of the four glucosyl residues from a branch point and transplants the short chain to a neighboring branch.
The last glycosyl unit is left to alpha 1,6-Glucosidase |
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What does alpha 1,6-Glucosidase do? What else is on the same tandem enzyme?
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After debranching enzyme moves 3 of the 4 glycosyl units left by phosphorylase, aslpha 1-6 glucosidase removes the last glycosyl subunit.
Debranching |
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What does phosphoglucomutase do?
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G1P --> G6P
|
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What does Glucose6-phosphatase do?
Where is it present? |
G6P +H2O --> G + Pi
In liver and proximal tubule of kidney. Therefore it is absent in muscles and muscle glycogen cannot produce glucose. |
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What inhibits phosphorylase?
What activates phosphorylase? Just for repetition, what does phosphoylase do? |
ATP
5'AMP (Glycogen)n glu + Pi --> (Glycogen)n-1 glu + Glu 1-P |
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When the serine residue on phosphorylase is phosphorylated, is phosphorylase more active or inactive?
Describe the glucagon cascade. |
ACTIVE
Glucagon --> Adenylyl Cyclase --> cAMP --> Phosphoryloase Kinase --> ACTIVE phosphorylase |
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What are G-proteins? Glucagon and epinephrine typically bind to ________ and activate a ___________.
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membrane proteins that relay hormonal signals to the interior of a cell.
Typically glucagon and epinephrine bind to a cell surface receptor and activate a G protein. |
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What is the substrate for glycolysis in muscle cells? How many ATP does each glycosyl unit yield as opposed to glucose? Why?
|
Glycogen
3 as opposed to 2 that the glucosyl unit is converted by phosphorylase to G 1-P, so we don’t need to spend an ATP to phosphorylate glucose. |
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What enzyme deficiency would increase outer branch length in glycogen? Decrease? What would happen to glycogen amount in these two cases?
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branching, debranching
normal, increased |
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What deficiency causes a massive increase in glycogen?
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alpha1,4 glucosidase
|
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What does glycogen synthase do?
(Glycogen)n glu + UDPG = (Glycogen)n+1 glu + UDP Where does it the residues it requires? |
It adds glycosyl residues to the non-reducing end of glycogen.
|
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What is the protein core of glycogen? What is the first glycosyl residue added to on the protein core?
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Glycogenin, tyr
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What does branching enzyme introduce?
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1-4 glycoside bonds
|
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What is Type I diabetes? How?
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Type I (Juvenile-Onset) diabetics lack insulin and therefore have elevated blood glucose levels as a result.
One way by which insulin lowers blood glucose levels is by stimulating glycogen synthase in the liver and in muscle. |
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What is the purpose of insulin?
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Insulin is a hormone that lowers blood glucose levels.
|
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How do Epinephrine and Glucagon raise blood glucose?
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Stimulating glycogen breakdown.
Stimulating gluconeogenesis. These hormones, through the G-protein system, lower the intracellular level of fructose 2,6 bisphosphate. This inhibits glycolysis at the PFK-1 step stimulates gluconeogenesis at the FBPtase step. |
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What is sucrose made of?
Maltose? Lactose? |
Fructose and Glucose
Glucose and Glucose Galactose and Glucose |
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Where can you find disaccharide splitting enzymes?
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covalently attached to the brush border of cells lining the small intestine
|
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What are symptoms of a lactase deficiency?
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Nausea
Abdominal fullness Diarrhea – Results from the fact that intestinal flora proliferate, and that water is retained in the colon as an osmotic consequence of unabsorbed lactose |
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What kind of people are typically lactose intolerant?
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Asians and blacks. So David and Sam. Except, I'm not lactose intolerant. I don't know about Sam.
|
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How is sucralose (Splenda) different from sucrose?
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Three –OH groups of sucrose are replaced by –Cl atoms.
Pure sucralose is 600 times sweeter than sucrose. |
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Summarize the step of galactose metabolism. What are the 4 steps? What is the net gain?
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Galactose + ATP = Gal 1-Phos + ADP
catalyzed by a kinase Gal 1-P + UDPGlu = UDP Gal + Glu 1-P catalyzed by a transferase UDP Gal = UDP Glu catalyzed by an epimerase Glu 1-P = Glu 6-P catalyzed by a mutase Net: Galactose + ATP = Glu 6-P + ADP ATP net yield: 2, from conv of gal to 2 pyr |
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What is galactosemia?
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A serious heritable disease resulting from a deficiency of the transferase
Gal 1-P + UDPGlu = UDP Gal + Glu 1-P catalyzed by transferase Gal 1-P and its metabolites accumulate, resulting in neural disease Effective treatment may be given if condition is diagnosed early enough |
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What are the 3 steps of fructose metabolism? How heavily regulated is the metabolism of fructose in the liver? What is the net yield?
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Fructose + ATP = Fructose 1-Phos + ADP
catalyzed by fructokinase Fructose 1-Phos = Glycerald. + DHAP catalyzed by aldolase B Glyceraldehyde + ATP = G 3-P + ADP catalyzed by a kinase Note that the PFK-1 step is bypassed. Hence the metabolism of fructose in the liver is essentially unregulated. ATP net yield: 2 from conversion of fructose to 2 pyr |
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What is fructosuria?
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Due to a deficiency of hepatic fructokinase
Result is that fructose is not phosphorylated and is excreted into the urine Not a serious disorder Fructose + ATP = Fructose 1-Phos + ADP catalyzed by fructokinase |
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What is Hereditary Fructose Intolerance (fructosemia)?
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A serious heritable disorder in which the aldolase B cleaving F 1-P into DHAP and glyceraldehyde is deficient
The result is that F 1-P and its toxic biproducts accumulate. This is a serious disorder. Fructose 1-Phos = Glycerald. + DHAP catalyzed by aldolase B |
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Where does fatty acid synthesis happen?
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liver and lactating mammary gland
|
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What are FA derived from? What supplies the energy for FA synthesis?
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Acetyl CoA
ATP and NADPH |
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Where does FA synthesis occur? What is shuttled prior to synthesis? Where does it comes from?
What are the 2 triggers of FA synthesis? |
cytosol
Acetyl CoA mitochondria high concentration of citrate and ATP |
|
What reaction is catalyzed by Acetyl acid carboxylase?
What is the coenzyme for carboxylase? |
The first step in FA synthesis: conversion of acetyl Coa to malonyl CoA
biotin |
|
How is Acetyl CoA carboxylase affected by phosphorylation/dephosphorylation?
How does citrate affect it? |
Phosphorylation deactivates the enzyme (in response to epinephrine, c-AMP, protein kinase cascade)
Dephosphorylation (due to insulin) activates the enzyme activate it |
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What catalyzes FA synthesis after the formation of malonyl CoA?
What are the general steps of the FA synthesis? |
Fatty acid synthase
Attach a malonyl group to ACP, then reduce to alkene. Then do it 7 times. |
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Where does elongation and desaturation of FA after palmitate?
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mitochondria and ER
|
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Where does the carbon for fatty acid synthesis come from? What is the reducing agent used?
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Acetyl CoA --> Malonyl CoA
NADPH |
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What are the 2 sources of NADPH for FA synthesis?
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hexose monophosphate pathway and the malic enzyme reaction that converts malate to pyruvate + NADPH in the cytosol
|
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Where does B-fatty acid oxidation occur?
How does the fatty acid get there? What inhibits this transfer? What is hurt by carnitine deficiency |
cytoplasm --> mitochondia
carnitine replaces CoA in Acyl CoA by acylcarnitine transferase I malonyl CoA muscle and cardiac |
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What is the first step of B-fatty acid oxidation? Where does this happen?
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FA are converted to acyl CoA by Fatty acyl CoA synthetase
cytoplasm |
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What happens in B-fatty acid oxidation after Acyl CoA is in the mitochondria?
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The acyl CoA is oxidized and eventually splits into a smaller acyl CoA and acetyl CoA. This continues until there is only acetyl CoA.
|
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What happens in beta oxidation of odd-chain fatty acids?
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Odd-chain FA degradation yields several acetyl CoAs and one propionyl CoA
Propionyl CoA is metabolized by carboxylation to methylmalonyl CoA (carboxylase is a biotin enzyme) Methyl carbon is moved within the molecule by methylmalonyl CoA mutase (one of only two Vitamin B12 cofactor enzymes) to form succinyl CoA |
|
What reaction requires vitamin B12?
What reaction is this? |
Formation of succinyl CoA from methylmalonyl CoA by methylmalonyl CoA mutase
Oxidation of odd numbered fatty acids |
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What happens to fatty acid chains longer than 20 carbons? What does this require? How do you regenerate the required material?
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Oxidized in peroxisomes and then shuttled to mitochondria
FAD Oxidation by molecular oxygen, forming H2O2 |
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What is a deficiency in peroxisomes? What is a defect in import of VLCFA into peroxisomes? What does this lead to?
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Zellweger syndrome
X-linked adrenoleukodystrophy Lead to accumulation of VLCFA Cause adrenal failure & loss of myelin in CNS & peripheral nerves |
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What cannot be oxidized by Beta oxidation? What happens in its place? What disease is associated?
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Branched-chain FA like phytanic acid cannot be oxidized by beta-oxidation
(Phytanic acid is in chlorophyl & some animal fats) These FA are hydroxylated on alpha carbon Genetic deficiency (Refsum disease) due to mutations in this pathway; leads to accumulation of this FA, causing neurologic & ophthalmologic problems |
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Are fatty acids generally glucogenic?
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Fatty acids are not glucogenic in animals
|
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What are ketone bodies? What are they used for?
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Excess acetyl CoA (from FA or carbohydrate degradation) is converted in liver to ketone bodies: acetoacetate, acetone, and β-hydroxybutyrate
To regenerate Acetyl CoA |
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How are excessive ketone bodies produced? What happens then?
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Excessive ketone bodies can be produced in diabetes mellitus or starvation (a lot of acetyl CoA in liver)
When rate of production exceeds utilization, ketonemia, ketonuria, and acidemia can result |
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Which ketone body is unstable? Which ketone body is not metabolized?
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acetoacetate
acetate |
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What are the 2 principle products of the pentose phosphate shunt?
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riboser-phosphate and NAPDH
|
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What is the starting point for the pentose phosphate pathway? What is the enzyme associated? What is produced?
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Glucose 6-P is converted to 6-phosphoglucono-lactone
Glucose 6-phosphate dehydrogenase (G6PD) NADPH |
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What is the cofactor for transketolase?
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TPP from thiamine Vitamin B1
|
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What do cells use NADPH for?
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Reductive biosynthesis
Maintenance of reduced glutathione Reduction of hydrogen peroxide Cytochrome P450 monooxygenase system Phagocytosis by white blood cells Synthesis of NO |
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How does NADPH keep glutathione reduced?
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breaks disulfide bond and puts Hs on the suflurs.
It maintains membrane stability |
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What are the basic properties and functions of the p450?
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Superfamily of hemoproteins that catalyze a variety of oxidation reactions
Some P450s are involved in biosynthesis of steroid hormones, bile acids & other molecules Some P450s detoxify foreign compounds |
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What does NADPH oxidase convert oxygen into? What is the product of this reaction used for? Which
cell types use this reaction? |
superoxide radical
killing microorganisms phagocytes |
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What role does NADPH play in No synthesis?
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NO is synthesized by NO synthase (NOS) from arginine, O2 and NADPH
|
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How many types of NO synthase are known? What are the names of the enzymes? What are their
properties/uses? |
eNOS (endothelium – constitutive) relaxes smooth muscle
nNOS (neural tissue – constitutive) iNOS (inducible in hepatocytes, monocytes/macrophages & neutrophils) makes ROS |
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What does NO do to cells?
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NO relaxes vascular smooth muscle (vasodilator) by stimulating cGMP production
This in turn activates cGMP-dependent protein kinase (leads to myosin light chain dephosphorylation) |
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How does NO participate in bactericidal activity?
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makes ROS with superoxide
|
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What cell type is chiefly affected in patients with glucose 6-P dehydrogenase deficiency? What can
happen to those cells because of this enzyme deficiency? What can precipitate pathologic episodes in this disease? 6 |
RBC
lyse Oxidant drugs Favism (from oxidizing agents in food, such as fava beans) Infection (from oxidants produced during inflammation) |
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How do the structure of GAGs and glycoproteins differ?
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GAGs are long, unbranched heteropolysaccharides with repeating amino and acidic sugars
glycoproteins- Glycoproteins have covalently attached carbohydrate chains (2-15 residues each; making up 2-60% of total molecular weight of protein). Either O or N linked |
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How do the properties of GAGs and glycoproteins differ?
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GAGs are Strongly negatively charged; therefore, they are extended, highly hydrated, compressible, and slippery
Constitute the body's ground substance and extracellular matrix; interact with fibrous proteins Abundant in skin, tendons, cartilage, ligaments, basement membranes, matrix of bone, etc. Glycoproteins- Integral membrane glycoproteins have various functions, including: cell surface recognition (receptors); antigenicity; adhesive proteins; receptors for viruses. In circulating glycoproteins, carbohydrate may provide protection from proteolysis. Lysomsomal acid hydrolases are also glycoproteins. |
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Which ones are mostly protein and which ones are mostly carbohydrate?
|
glycoproteins
GAGs |
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Which ones have linear carbohydrate chains and which ones have branched carbohydrates?
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GAGs
glycoproteins |
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In very general terms, how do the modes of synthesis for GAGs and glycoproteins differ? Where in the cell are they made?
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GAGs- Activated UDP-sugars are used by specific transferases (recall glycogen)
Reactions occur in the ER and Golgi because GAGs and proteoglycans are exported from cells Basically, core protein enters ER and is glycosylated As with GAGs, O-linked glycosides are added one sugar at a time in the ER and Golgi to protein by specific glycosyltransferases. N-Linked glycoside synthesis involves a lipid intermediate (dolichol pyrophosphate). Glycosyltransferases add N-acetylglucosamine, mannose, and glucose to the dolichol pyrophosphate. The oligosaccharide is then transferred to the protein asparagine group by a protein-oligosaccharide transferase, in the ER. The N-linked oligosaccharide is further processed by removal of specific glucose and mannose residues and addition of other specific sugars, usually capped by N-acetylneuraminic acid (sialic acid) residues. Fate of N-linked glycoproteins is secretion, exposure on cell surfaces; also delivery to lysosomes. |
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What basic building blocks of GAGs and glycoproteins and what are they made from?
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Glycosaminoglycans consist of repeating disaccharide units,
sialic acid found in gangliosides and glycoproteins target for some pathogenic organisms UDP-glucuronic acid is formed by oxidation of UDP-glucose using NAD and H2O. + Glucuronic acid is also used in detoxification reactions, e.g., bilirubin excretion. D-Glucuronate also is the precursor for L-Ascorbate (vitamin C). Primates and guinea pigs lack the enzyme necessary for this reaction; hence, ascorbate is a vitamin in humans. Glycoprotein precursors are activated sugar nucleotides UDP-sugars (UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine) GDP-sugars (GDP-mannose, GDP-L-fucose) CMP-N-acetylneuraminic acid |
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What basic functions do they fulfill?
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GAGs
Heparin- anticoagulant Sialic acids- target for pathogens |
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How and where are GAGs and glycoproteins degraded?
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Glycosaminoglycans turn over (half-lives: 3-120 days).
Phagocytosis lysosomes; digested by acid hydrolases (pH ~5) Degradation involves many enzymes, starting with endoglycosidases, followed by sequential degradation of oligosaccharides, by removal of sulfate groups and individual monosaccharides from non-reducing end. Degradation of glycoprotein is similar to that of proteoglycans. It occurs in lysosomes by acid glycosidases. As with GAGs, degradation is generally the reverse of synthesis. Circulating glycoproteins trimmed of sialic acid residues are recognized and removed by asialoglycoprotein receptors in the liver. |
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What type of diseases result from inability to degrade GAGs and glycoproteins?
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Numerous defects in lysosomal enzymes lead to mucopolysaccharidoses = accumulation of GAGs in tissues, and excretion of oligosaccharides in urine. Pathology depends on enzyme defect and severity.
Lipidosis and glycoprotein oligosaccharidosis may also occur because lysosomal enzymes also degrade glycolipid and glycoprotein carbohydrate components. I-cell disease is a defect in this specific phospho-transferase. This results in deficiency of all lysosomal enzymes (acid hydrolases) in the lysosomes. |
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What is the structure of triglycerides and FA like?
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Triglycerides have a glycerol backbone and have 3 FA chains attached. FA are acids that have alkane/alkene chaines attached.
|
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What is the structure of phospholipids like?
|
Phospholipids are amphipathic molecules
Head group = alcohol attached via phosphodiester linkage to either: diacylglycerol (glycerophospholipid) or sphingosine (sphingophospholipid = sphingomyelin). |
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What is the structure of cholesterol like?
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The structure of cholesterol consists of 4 fused rings, a hydrocarbon “tail”, -OH group on C-3 and double bond at C-5 to C-6
These are reactive sites for esterification and oxidation-reduction reactions |
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How do the intestines digest FA?
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Biles emulsify fats and form micelles.
Cholestrin signals for the creation of more bile and pancreatic enzymes. If the pH is too low, secretin signals for the release of bicarbonate. Pancreatic lipase takes care of TGs. PLs and CEs are also hydrolyzed. Micelles take up the hydrolysis products then release them through the brush border. Then they are packed with ap48 (reesterification?) and sent off in chylomicrons |
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How are dietary lipids packaged and transported through blood?
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in chylomicrons --> lymph --> blood
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How are fatty acids from triacylglycerols absorbed when the chylomicrons get to the capillaries in tissues?
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hydrolyzed by lipoprotein lipase
fatty acids absorbed by cells or transported in blood bound to albumin glycerol is released to liver |
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Where does the glycerol go?
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metabolized by the liver into Glycerol-3-P
|
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What are the precursors for formation of triacylglycerols in the liver/adipose tissue?
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Glycerol-3-P from glycolysis
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What is the precursor for arachidonate?
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Linoleate
|
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Linoleic acid and linolenic acid are essential fatty acids – why?
|
we cannot add double bonds past carbon 9
|
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Where does de novo synthesis of fatty acids occur (i.e., in which cellular compartment)?
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cytosol (there's a transfer involved)
|
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What is the key first step of de novo fatty acid synthesis, and how is it regulated?
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Acetyl CoA carboxylase
acetyl CoA --> malonyl CoA enzyme activated by citrate and deactivated by fatty acyl CoA |
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What is the acyl carrier protein and what is its general role in fatty acid synthesis?
|
the ACP holds onto the growing FA chain and then releases it after it becomes palmitate
|
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In which cellular compartment does beta-oxidation of fatty acids occur?
|
MATRIX
|
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What is carnitine’s role in fatty acid catabolism?
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Carries Acyl CoA (minus CoA) into the mitochondria)
|
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What is the general outline of fatty acid synthesis, and how does it compare to the process of beta-oxidation
of fatty acids? |
They are opposites.
FA synthesis: The FA is reduced and carbons are added Beta oxidation: the beta carbon is oxidized and broken off the FA |
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Why can’t most of the carbon atoms from fatty acids be used to make glucose?
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You can't go from acetyl CoA to pyruvate
|
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What organ produces ketone bodies? From what starting material?
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Excess acetyl CoA (from FA or carbohydrate degradation) is converted in liver to ketone bodies: acetoacetate, acetone, and β-hydroxybutyrate
|
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What are the 3 keton bodies?
|
acetoacetate, acetone, and β-hydroxybutyrate
|
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What are ketone bodies used for?
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to regenerate acetyl CoA for use in the TCA cycle
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Which ketone body is non-metabolizable?
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acetone
|
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When are ketone bodies used?
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When carbohydrate concentration is love
|
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Can ketone bodies be used to make glucose?
|
No
|
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How do sphingolipids differ from glycerophospholipids?
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They are attached to either: sphingosine (sphingophospholipid = sphingomyelin) or diacylglycerol (glycerophospholipid)
|
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what are the roles of phospholipids & glycolipids?
|
Phospholipids are major constituents of all cell membranes, components of bile, anchors of some proteins
in membranes, signal mediators, components of lung surfactant, and components of lipoproteins. Glycolipids have important roles in cell interactions, growth, and development. They are very antigenic (e.g., blood group antigens); act as surface receptors for some toxins and viruses; and undergo major changes during cell transformation |
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How are phospholipids and glycolipids degraded? In which cellular compartment does this take place?
|
Glycerophospholipid degradation occurs by phospholipases present in tissues (membrane bound or free), pancreatic juice, and venoms
Sphingomyelin is degraded in lysosomes by sphingomyelinase to give ceramide, and ceramidase to give sphingosine Niemann-Pick disease is due to sphingomyelinase deficiency Degradation of glycosphingolipids occurs in lysosomes after endocytosis of membrane portions A series of acid hydrolases participate in the degradation Degradation is sequential in the order: last on, first off |
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What causes lipidoses such as Niemann-Pick disease?
|
Niemann-Pick disease is due to sphingomyelinase deficiency
Sphingomyelin is degraded in lysosomes by sphingomyelinase to give ceramide, and ceramidase to give sphingosine |
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How are eicosanoids derived?
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linoleic acid --> Arachidonate
|
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What are eicosanoids and what do they do?
|
specialized FAs that have strong hormone-like actions in the tissues where they are produced.
They cause: vasodilation, constriction, platelet aggregation, inhibition of platelet aggregation, contraction of smooth muscle, chemotaxis of leukocytes, release of lysosomal enzymes |
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Which classes of eicosanoids are formed by the action of cyclooxygenase, and which by lipoxygenase?
|
prostaglandins
leukotrienes |
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What classes of drugs inhibit cyclooxygenase? How do their mechanisms differ?
|
Corticosteroids (e.g., cortisol) inhibit at the level of phospholipase A2
Antiinflammatory drugs (NSAIDS) like indomethacin & ibuprofen reversibly inhibit COX Aspirin irreversibly inactivates COX |
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Where is cholesterol synthesized?
|
Cholesterol is a lipid synthesized by virtually all cells, but especially liver, intestine, adrenal cortex, and reproductive tissues
|
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What is the source of the carbon atoms in cholesterol?
|
acetyl CoA
|
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What is the key regulatory enzyme in cholesterol synthesis? What class of drugs inhibit this enzyme?
|
HMG CoA reductase
statins |
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Describe the flow of lipoproteins from HDL to CM to VLDL to IDL back to HDL.
|
Chylomicrons (CM) are synthesized in the intestine, enter lymph and then blood. Nascent CM pick up apoE and apoCs from HDL.
In the capillaries of adipose tissue, lipoprotein lipase (LPL) degrades triacylglycerol (TG) of chylomicrons to fatty acids (FA) and glycerol which enter tissues by diffusion After most of the TG is removed, chylomicrons become chylomicron remnants Chylomicron remnants bind to specific receptors on the surface of liver cells through apo E component; the complex is endocytosed Chylomicron remnants deliver dietary cholesterol and some cellular cholesterol (via HDL) to the liver. Chylomicrons and remnants are cleared from circulation in over 9 hrs Liver synthesizes TG and cholesterol and packages them into VLDL for export Nascent VLDL pick up apoE and apoCs from HDL In the capillaries of various tissues, lipoprotein lipase (LPL) degrades TG to FA and glycerol, which enter the tissues by diffusion. (ApoC-II activates lipoprotein lipase.) VLDL remnants are called IDL Further lipoprotein lipase action converts IDL into LDL LDL receptors exist in the liver (50%) and in most peripheral tissues (50%) (apoB-100/apoE receptors) The complexes of LDL and receptor are taken into the cells by endocytosis, where LDL is degraded but the receptors are recycled HDL protein components are synthesized in the liver and intestine Small nascent HDL can diffuse close to peripheral cell membranes where HDL picks up cholesterol Back in circulation lecithin cholesterol acyltransferase (LCAT) converts cholesterol to CE on HDL Some of the CE is transferred from HDL to other lipoproteins by cholesterol ester transfer protein Part of this CE ends up in the liver HDL particles bind to SRB1 receptors on adrenal cells, gonads, and the liver, and deliver cholesterol esters for synthesis of steroid hormones and bile salts for excretion |
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What are they 5 classes of lipoproteins? What lipids do they transport?
|
Chylomicrons and VLDL mainly transport TG
IDL, LDL, and HDL mainly transport CE |
|
What is the role of LDL (especially oxidized LDL) in atherosclerosis?
|
LDL is taken up by macrophages to become foam cells which form plaques
|
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What does HDL do and why are high HDL levels protective against atherosclerosis?
|
Small nascent HDL can diffuse close to peripheral cell membranes where HDL picks up cholesterol, preventing plaque formation
HDL cholesterol levels are inversely related to risk of cardiovascular disease |
|
What are “good cholesterol” and “bad cholesterol”?
|
HDL, LDL
|
|
How is cholesterol degraded?
|
Humans cannot degrade cholesterol to CO2 and H2O
Rather, the ring system is eliminated in the feces as unmodified cholesterol, bile acids, or reduced cholesterol by bacteria (cholestanol and coprostanol) |
|
How are bile salts recycled?
|
Bile salts and bacterial products are efficiently reabsorbed in the intestine and returned via the portal vein to the liver for resynthesis
Of 15-30 g of bile salts secreted/day, only 0.5 g are lost in feces (i.e., 0.5 g of cholesterol is excreted) |
|
What are the general classes of steroid hormones, and what are their overall precursors?
|
glucocorticoids
mineralocorticoids androgens estrogens progestins cholesterol |
|
In what part of the body does FA synthesis occur?
|
Synthesis of Fatty Acids (FA) occurs primarily in the liver and lactating mammary gland, less so in adipose tissue
|
|
What is the carbon source in FAs?
|
acetyl CoA
|
|
Why does a decrease in PFK-1 cause a decrease in lactate production?
|
PFK-1 allows F6P --> F2,6BP
this produces NAD+ from NADH indirectly. Lactate production restores NADH. There is less of a need for lactate production. |
|
Why does a PFK-1 deficiency have different reactions under aerobic and anaerobic conditions?
|
Under aerobic conditions, one can use oxidation of fatty acids.
Under anaerobic conditions, they use glycolysis. |
|
Why did the PFK-1 patient also have hemolysis?
|
The rbcs did not have energy.
|
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Why did glycogen accumulate with PFK-1 deficiency in the muscles?
|
no glycolysis.
|
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What does DNOC do?
|
Uncouples mitochondrial respiration so etc is unproductive.
|
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What is an uncoupler of oxidative phosphorylation? How do uncouplers function, in molecular terms?
|
ncouplers of oxidative phosphorylation in mitochondria inhibit the coupling between ETC and phosphorylation reactions and thus inhibit ATP synthesis without affecting the respiratory chain and ATP synthase .
|
|
How do uncouplers function, in molecular terms?
|
DNOC dissipates the H+ electrochemical gradient
|
|
why KCN blocked oxygen consumption after DNOC, while oligomycin did not
|
KCN blocks terminal step in ETC
Oligomycin interferes with the ability of the ATP synthase to utilize the H+ electrochemical gradient. |
|
Why was the respiration rate and body temperature elevated in these patients?
|
-DNOC causes mitochondria to work harder but unproductively . Large amounts of metabolic fuel are consumed with the released energy being wasted as heat = fever
-The extra energy demand for the uncontrolled respiration are fatty acids that are taken from triglyceride stores. The accompanying excessive oxygen consumption leads to tissue hypoxia, which the body attempts to alleviate by increased pulmonary respiration. |
|
Are there physiologic equivalents to DNOC?
|
Aromatic weak acids are thought to pass readily across the mitochondrial inner membrane in their undissociated form thus dissipating the electrochemical gradient
|
|
Could DNOC work as a reducing aid?
|
Yes
|
|
Understand how changes in the blood levels of LDH and CK isozymes aid in diagnosing MI
|
- Lactate Dehydrogenase has 5 isoenzymes that tissue specific and depending on which isoenzyme we find we will know what cells have been damaged and creatine kinase has two subunits that are also tissue specific. These two cytosolic proteins are normally efficiently retained inside cells but tissue damage may compromise membrane integrity and they may flow out. They can then be measured and an MI may be diagnosed if the appropriate isoenzyme is found in the blood stream.
|
|
How does the immuno-inhibition test of CK isozymes work?
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The antibody binds to and inhibits the activity of M subunits leaving the activity of B subunits unaffected. Remaining CK activity is assumed to be due only to CK-MB since significant amounts of CK-BB are rarely found in serum. This allows you to isolate that the CK that we are interested in to Diagnose for an MI. CK-MB is from the myocardium.
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How does tPA work, and when must it be given?
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tPA is tissue type plasminogen activator, it forms plasmin from plasminogen. Plasmin is important because it dissolves blood clots. tPA must be given very shortly after the onset of ischemic symptoms (aprox 3hrs) to prevent blood clots from forming.
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Understand the biochemical basis for oral rehydration therapy
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secondary Na glucose transport system is unaffected by cholera toxin
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How does cholera toxin act, in molecular terms?
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Stops GTPase activity. AC increases. Secretion of water and salt --> diarrhea
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What is the protein target of cholera?
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alpha unit of G protein
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How does cholera toxin modulate its activity?
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infected cells are eventually killed and expelled in feces
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Why is starch better than glucose?
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In can be broken down into two molecules which speeds up rehydration without pulling out more water through osmosis.
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Where are acid hydrolases?
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Lysosomes
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How are acid hydrolases targeted to lysosomes?
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Mannose 6 phosphate tag
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What happens when acid hydrolases lack mannose 6 phosphate tag?
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I cell disease
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Understand how the cytochrome P450 enzyme system functions.
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– Hydroxylation involves a specialized electron transport system bound to the membranes of the smooth endoplasmic reticulum. NADPH provides the reducing power via a specialized cytochrome system, cytochrome p450.
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What do C450 do to xenobiotics and toxins?
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Make them soluble and excretable
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What are the cosubstrates for cytochrome P450?
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NADPH & oxygen
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Why are drugs or xenobiotics sometimes glucuronidated?
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Because they become more water soluble after the processes.
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What natural substance in our bodies is processed by glucuronidation?
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2- Napthylamine
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Know the steps by which 2-napthylamine is converted into a carcinogen.
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2- napthylamine + NADPH+ UDP- glucuronic acideà NHNGP (In the liver)
2- naphthylamine + Bladder tissueà N-acetyl-2- naphthylamine When the pH was dropped to 5.5-6.5 N-glycosidic bond in NHNGP was readily hydrolysed. One of the products was strongly reactive with DNA. |
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Why does 2-napthylamine cause bladder and not liver cancer?
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pH is necessary for the production of the carcinogen
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