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87 Cards in this Set
- Front
- Back
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Vitamin A (retinol)
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Fat soluble. Deficiency leads to night blindness, dry skin. Forms part of visual pigments. Found in leafy vegetables.
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Vitamin B1 (thiamine)
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Water soluble. Deficiency causes Beriberi (wet- dilated cardiomyopathy, edema; dry- polyneuritis, muscle wasting) and Wernicke-Korsakoff syndrome (encephalopathy and psychosis) Seen in alcoholism and malnutrition. Acts as cofactor in oxidative decarboxylation of a-ketoacids (pyruvate, a-ketoglutarate, important in maple syrup urine disease) and as a cofactor for transketolase in the pentose phosphate (HMP) shunt.
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Vitamin B2 (riboflavin)
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Water soluble. Deficiency causes angular stomatitis, cheilosis, corneal vascularization. Acts as a cofactor in oxidation and reduction (the F in FADH2)
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Vitamin B3 (niacin)
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Water soluble. Deficiency leads to pellegra (glossitis, dermatitis, diarrhea, dementia, death). Can be caused by Hartnup's disease (decreased tryptophan absorption, which can be converted into niacin with vitamin B6), carcinoid syndrome (increased tryptophan metabolism), INH (related to decreased B6), poor diet ("corn based" is classic). Cofactor of Redox reactions (the N in NAD, NADPH)
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Vitamin B5 (pantothenate)
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Water soluble. Deficiency causes dermatitis, enteritis, alopecia, adrenal insufficiency. It is part of CoA and a component of fatty acid synthesis.
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Vitamin B6 (pyridoxine)
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water soluble. Deficiency leads to convulsions, hyperirritability, peripheral neuropathy. Acts as a cofactor in transamination (eg ALT and AST), decarboxylation, and heme synthesis. Used in conversion of tryptophan to niacin. Decreased absorption due to INH or oral contraceptives.
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Vitamin B12 (cobalamin)
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Taken up in conjunction with intrinsic factor in the terminal ileum. Large reserve stored in the liver. Deficiency leads to macrocytic, megaloblastic anemia, neurological symptoms (abnormal myelin), glossitis. Synthesized by microorganisms. Acts as cofactor for homocysteine methylation (--> methionine + THF) and methylmalonyl-CoA handling (--> Succinyl CoA). Deficiency caused by malabsorption (sprue, enteritis, fish tapeworm D. latum), lack of intrinsic factor (pernicious anemia), absence of terminal ileum (as in Crohn's disease).
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Folic acid (folate)
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Water soluble. Deficiency leads to macrocytic, megaloblastic anemia, and neural tube defects in pregnancy--no neurological symptoms as in B12 deficiency, however. Acts as coenzyme (tetrahydrofolate) for 1-carbon transfers. Important for synthesis of bases in DNA and RNA. Not stored by body, obtained from leafy greens, fortified grain products. Sulfa drugs target the folate precursor in bacteria (ie they are PABA analogs)
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Biotin
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water soluble. Deficiency causes dermatitis, enteritis; it can be caused by antibiotic use or ingestion of raw eggs (avidin protein binds biotin). Acts as cofactor for carboxylations.
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Vitamin C (ascorbic acid)
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Water soluble. Deficiency causes scurvey. Necessary for hydroxylation of proline and lysine in collagen synthesis/cross-linking. Facilitates iron absorption. Necessary cofactor for DA-->NE conversion.
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Vitamin D
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Fat soluble. D2 consumed in fortified dairy, D3 produced during sun exposure, 25-OH D3 storage form, 1,25(OH)2 D3 is the active form. Acts to regulate calcium ion metabolism (absorption, in conjunction with PTH for bone, kidney calcium homeostasis). Converted to active form in the kidney stimulated by PTH. Deficiency causes rickets (in children), osteomalacia (in adults). Excess can lead to hypercalcemia, calcification of soft tissue, bone demineralization, hypercalciuria which can lead to kidney stones.
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Vitamin E
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Fat soluble. Antioxidant important for protecting erythrocytes from hemolysis. Found in leafy greens, seed grains.
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Vitamin K
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Fat soluble. Produced by gut bacteria so deficiency generally seen in neonates or those treated with oral antibiotics and have a poor diet (esp. no green vegetables). Required for synthesis of clotting factors (II, VII, IX, X, proteins C and S); deficiency leads to increased PT and PTT but normal bleeding time (platelets unaffected); impared clotting with bruising and hemorrhage. Several important drugs interfere with Vit. K metabolism (Warfarin, for example).
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Zinc
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Deficiency leads to delayed wound healing, hypogonadism, decreased axillary/pubic/facial hair, may predispose alcoholics to cirrhosis. Important component of many metalloenzymes. Inhalation of fumes can lead to neurological damage, excessive ingestion can lead to vomiting/diarrhea.
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Calcium
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Essential for bones and teeth, normal nerve and muscle function, blood clotting. Deficiency can cause parasthesias, bone fractures/pain/loss of height, osteomalacia.
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Vitamin A (retinol)
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Fat soluble. Deficiency leads to night blindness, dry skin. Forms part of visual pigments. Found in leafy vegetables.
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Vitamin B1 (thiamine)
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Water soluble. Deficiency causes Beriberi (wet- dilated cardiomyopathy, edema; dry- polyneuritis, muscle wasting) and Wernicke-Korsakoff syndrome (encephalopathy and psychosis) Seen in alcoholism and malnutrition. Acts as cofactor in oxidative decarboxylation of a-ketoacids (pyruvate, a-ketoglutarate) and as a cofactor for transketolase in the pentose phosphate (HMP) shunt.
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Vitamin B2 (riboflavin)
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Water soluble. Deficiency causes angular stomatitis, cheilosis, corneal vascularization. Acts as a cofactor in oxidation and reduction (the F in FADH2)
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Vitamin B3 (niacin)
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Water soluble. Deficiency leads to pellegra (glossitis, dermatitis, diarrhea, dementia, death). Can be caused by Hartnup's disease (decreased tryptophan absorption, which can be converted into niacin with vitamin B6), carcinoid syndrome (increased tryptophan metabolism), INH (related to decreased B6), poor diet ("corn based" is classic). Cofactor of Redox reactions (the N in NAD, NADPH)
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Vitamin B5 (pantothenate)
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Water soluble. Deficiency causes dermatitis, enteritis, alopecia, adrenal insufficiency. It is part of CoA and a component of fatty acid synthesis.
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Vitamin B6 (pyridoxine)
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water soluble. Deficiency leads to convulsions, hyperirritability, peripheral neuropathy. Acts as a cofactor in transamination (eg ALT and AST), decarboxylation, and heme synthesis. Used in conversion of tryptophan to niacin. Decreased absorption due to INH or oral contraceptives.
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Vitamin B12 (cobalamin)
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Taken up in conjunction with intrinsic factor in the terminal ileum. Large reserve stored in the liver. Deficiency leads to macrocytic, megaloblastic anemia, neurological symptoms (abnormal myelin), glossitis. Synthesized by microorganisms. Acts as cofactor for homocysteine methylation (--> methionine + THF) and methylmalonyl-CoA handling (--> Succinyl CoA). Deficiency caused by malabsorption (sprue, enteritis, fish tapeworm D. latum), lack of intrinsic factor (pernicious anemia), absence of terminal ileum (as in Crohn's disease).
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Folic acid (folate)
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Water soluble. Deficiency leads to macrocytic, megaloblastic anemia, and neural tube defects in pregnancy--no neurological symptoms as in B12 deficiency, however. Acts as coenzyme (tetrahydrofolate) for 1-carbon transfers. Important for synthesis of bases in DNA and RNA. Not stored by body, obtained from leafy greens, fortified grain products. Sulfa drugs target the folate precursor in bacteria (ie they are PABA analogs)
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Biotin
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water soluble. Deficiency causes dermatitis, enteritis; it can be caused by antibiotic use or ingestion of raw eggs (avidin protein binds biotin). Acts as cofactor for carboxylations.
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Vitamin C (ascorbic acid)
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Water soluble. Deficiency causes scurvey. Necessary for hydroxylation of proline and lysine in collagen synthesis/cross-linking. Facilitates iron absorption. Necessary cofactor for DA-->NE conversion.
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Vitamin D
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Fat soluble. D2 consumed in fortified dairy, D3 produced during sun exposure, 25-OH D3 storage form, 1,25(OH)2 D3 is the active form. Acts to regulate calcium ion metabolism (absorption, in conjunction with PTH for bone, kidney calcium homeostasis). Converted to active form in the kidney stimulated by PTH. Deficiency causes rickets (in children), osteomalacia (in adults). Excess can lead to hypercalcemia, calcification of soft tissue, bone demineralization, hypercalciuria which can lead to kidney stones.
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Vitamin E
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Fat soluble. Antioxidant important for protecting erythrocytes from hemolysis. Found in leafy greens, seed grains.
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Vitamin K
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Fat soluble. Produced by gut bacteria so deficiency generally seen in neonates or those treated with oral antibiotics and have a poor diet (esp. no green vegetables). Required for synthesis of clotting factors (II, VII, IX, X, proteins C and S); deficiency leads to increased PT and PTT but normal bleeding time (platelets unaffected); impared clotting with bruising and hemorrhage. Several important drugs interfere with Vit. K metabolism (Warfarin, for example).
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Zinc
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Deficiency leads to delayed wound healing, hypogonadism, decreased axillary/pubic/facial hair, may predispose alcoholics to cirrhosis. Important component of many metalloenzymes. Inhalation of fumes can lead to neurological damage, excessive ingestion can lead to vomiting/diarrhea.
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Calcium
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Essential for bones and teeth, normal nerve and muscle function, blood clotting. Deficiency can cause parasthesias, bone fractures/pain/loss of height, osteomalacia.
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Iodine
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Incorporated in thyroid hormones. Deficiency leads to goiter, cretinism (retarded growth and development). Excessive iodine can also cause goiter by blocking organification (incorporation in to thyroid hormones).
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Iron
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Important for oxygen transport (hemoglobin/myoglobin), electron transport (cytochromes), activation of oxygen (oxidases/oxygenases). Absorbed more efficiently as heme iron. Absorption enhanced by Vit C; antacids and certain plant products reduce absorption. Deficiency leads to hypochromic, microcytic anemia, fatigue, pallor, shortness of breath on exertion. Excess leads to hemochromatosis (seen with repeat transfusions, hereditary iron storage issues).
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Magnesium
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Involved in enzyme activity, particularly in most ATP-linked reactions. Deficiency seen most often in alcoholics, those with fat or other malabsorption syndromes. Leads to increased neuromuscular excitability (muscle spasms, parasthesias, if prolonged tetany, seizures, coma), if severe can also lead to depression of PTH release leading to hypocalcemia.
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Phosphorus
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Used in bone mineralization, as a blood buffer, constituent of nucleic acids, phospholipids, etc. Deficiency very rare.
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Kwashiorkor vs Marasmus
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Kwashiorkor - protein calorie malnutrition. Edema, skin and hair changes, enlarged liver w/fatty changes, intestinal mucosal atrophy (malabsorption etc), increased abdominal girth.
Marasmus - complete malnutrition (both calories and protein), loss of subQ fat, muscle wasting, frequent infection, low body temp, extremely slowed growth, death |
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Alcohol metabolism
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EtOH (via alcohol dehydrogenase, NAD+)--> Acetaldehyde (via Acetaldehyde dehydrogenase, NAD+)--> acetate
NAD+ limiting reagent. Disulfram inhibits acetaldehyde dehydrogenase, leads to acetaldehyde accumulation and awful hangover symptoms (metronidazole, anti-fungal griseofulvin, other drugs have same effect) |
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Ethanol hypoglycemia mechanism
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ethanol metabolism increases NADH to NAD+ ratio in the liver (EtOH + 2NAD+-->acetate + 2NADH) causing diversion of pyruvate to lactate and OAA to malate, inhibiting gluconeogenesis. Altered NADH/NAD+ ratio responsible for liver fatty change in chronic alcoholics (shunts from glycolysis to fatty acid synthesis)
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Topoisomerases (gyrases)
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relieve supercoil tension by nicking helix
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Primase
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creates RNA primer on with DNA polymerase III can initiate replication
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DNA polymerase III
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Elongates DNA chain by adding deoxynucleotides to the 3' end until it reaches the next RNA primer. Has 3'->5' exonuclease proofreading activity, not 5'->3' exonuclease activity.
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DNA polymerase I
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Degrades RNA primer (5'->3' exonuclease activity) and fills in the gap with DNA.
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DNA ligase
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seals DNA fragments
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Nucleotide excision repair - mechanism and one related disease
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endonucleases cut out the nucleotides with damaged bases; gaps filled by DNA polymerase I, sealed by ligase. Defective in xeroderma pigmentosa (leads to inability to repair UV damage i.e. pyrimidine damage, multiple skin cancers)
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Base excision repair - what is the mechanism?
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Specific removal of damaged nitrogenous bases by glycosylases; AP endonuclease removes empty sugar, gap filled and resealed.
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mismatch repair
what is the process? What is a disease related to defective mismatch repair? |
New strand is unmethylated and therefore recognized. Mismatched nucleotides removed, gap filled and resealed. Process is defective in HNPCC (early colon cancer, elevated risk of other GI and reproductive cancers, esp endometrial cancer)
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DNA, RNA, protein synthesis directions
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DNA, RNA: 5' --> 3'
proteins: N --> C (5->3 on mRNA) 5' is the triphosphate (energy for bond formation), 3' is the hydroxyl target for bond formation |
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RNA polymerases
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I --> rRNA
II --> mRNA III --> tRNA this is also the order each RNA is used in translation to proteins. There is no proofreading function (no 3'->5' exonuclease activity) but can initiate chains (does not need primer) RNA polymerase II is able to open DNA at promoter site to begin transcription; inhibited by a-amanitin (found in death cap mushrooms) Prokaryotes only have 1 RNA polymerase complex that makes all types of RNA (inhibited by rifampicin) |
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mRNA start codon
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AUG (or rarely GUG) --> Codes for methionine. (AUG inAUGurates protein synthesis)
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mRNA stop codons
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UGA, UAA, UAG
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Promotor
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Site where RNA polymerase (II in eukaryotes) and other transcription factors bind to DNA 25-70 bp upstream from gene locus. TATA box, CAAT box are examples. Mutation in promoter generally leads to significant decrease in transcription of gene
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Enhancer
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Stretch of DNA that alters expression of gene by binding transcription factors. Can be practically anywhere in the genome.
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Operator
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Sight where negative regulators bind. Mutation here can prevent downregulation of gene transcription by preventing repressor binding
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Introns vs exons
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exons --> expressed segments
introns --> intervening segments splicing connects exons, can sometimes be combined in different combinations to form different proteins in various tissues (alternative splicing) |
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mRNA splicing
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(exon1)GU----A----AG(exon2)
transcript combines with snRNPs to form spiceosome, forms lariat -shaped intermediate, released to remove intron and connect to exons. |
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Eukaryote RNA processing
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Occurs in the nucleus post-transcription.
1) 5' capping with 7-methylguanine to prevent digestion by nucleases and help align mRNA during translation 2) polyadenylation on 3' end (around 200 A's) 3) splicing out of introns (all begin with GU and end with AG and have an A in the center on which the lariat is formed) Before processing, hnRNA; After processing, mRNA |
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tRNA structure
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75-90 nucleotides; cloverleaf form; anticodon end opposite 3' aminoacyl end. All have CCA at 3' end to which the AA is covalently bound and a high percentage of modified bases.
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tRNA charging
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Aminoacyl-tRNA sythetase (1 per AA) attaches AA to tRNA using ATP. Proofreads attachment; if incorrect hydrolyze the bond. AA-tRNA bond contains the energy for formation of peptide bond.
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Initiation of protein synthesis
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Initiation factors help assemble small ribosomal subunit, initiator tRNA-Methionine, mRNA, and GTP (ATP hydrolysis in this step). Large subunit binds the initiation complex and methionine-tRNA positioned at P site; GTP hydrolized and IFs released.
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Protein elongation
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1. AA-tRNA bind to the A site of the protein synthesis complex (large ribosomal subunit)
2. Peptidyl transferase catalyzes peptide bond formation and transfers the growing polypeptide to the AA in the A site 3. ribosome advances 3 nucleotides (1 codon) toward the 3' end of the mRNA, moving the peptidyl-tRNA to the P site. A site->P site->E site (empty tRNA exits) |
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Termination of protein synthesis
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ribosome encounters a nonsense (stop) codon; Protein releasing factor and GTP bind to the site. Peptidyl transferase hydrolyzes peptidyl-tRNA releasing the completed polypeptide (GTP hydrolysis occurs). Ribosomal subunits dissociate.
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Nissl bodies
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RER of neurons that synthesize enzymes and peptide neurotransmitters.
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Drugs acting on microtubules (aB dimers form cylinders that slowly polymerize/rapidly depolymerize, part of flagella, cilia, mitotic spindles)
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Mebendazole/thiabendazole (antihelminth)
Taxol (breast cancer chemotherapy) Griseofulvin (antifungal) Vincristine/Vinblastine (cancer chemo) Colchicine (anti-gout) |
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Chediak-Higashi syndrome
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Microtubule polymerization defect resulting in decreased phagocytosis. Prone to infection (esp. Staph aureus)
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Kartagener's syndrome
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Immotile cilia due to a defect in dynein arm. Results in infertility (both M and F), bronchiectasis, recurrent sinusitis. Associated with situs inversus (flipped organ location)
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dynein vs kinesin
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dynein - ATPase minus-end directed motors. In cilium, link peripheral microtubule doublets and causes bending by differential sliding of doublets.
kinesin - plus-end directed ATPase motors (move opposite direction of dynein along microtubules). |
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Ouabain
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inhibitor of Na/K pump (binds K+ site)
Cardiac glycosides (ie digoxin) also inhibit the Na/K pump |
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Collagen type I
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90% of collagen in body
Make up bone, skin, tendon, dentin, fascia, cornea |
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Collagen type II
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Cartilage, vitreous, nucleus pulposus (in vertabrae)
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Collagen type III
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also known as Reticulin. Skin, blood vessels, uterus, fetal tissue, granulation tissue
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Collagen IV
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basement membrane/basal lamina (Goodpasture's syndrome is an autoimmune process directed against type IV collagen)
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Steps of collagen production
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1. translation of preprocollagen in the RER (every 3rd amino acid is Gly, others are usually proline, hydroxyproline, or hydroxylysine)
2. hydroxylation of specific proline and lysine residues in the ER (requires vitamin C). Scurvy inhibits. 3. Glycosylation of pro-a-chain lysine residues and formation of procollagen (triple helix of 3 collagen a chains) in the Golgi. Defective in osteogenesis imperfecta. 4. Exocytosis of procollagen into ECM 5. Proteolytic cleaving of terminal regions transforming procollagen into tropocollagen. Defective in Ehlers-Danlos syndrome. 6. crosslinking of many staggered tropocollagen molecules with covalent lysine-hydroxylysine cross linkages (by lysyl oxidase) to make collagen fibrils. |
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Ehlers-Danlos syndrome
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Hyperextensible skin, tendency to bleed/easy bruising, hypermobile joints. Associated with berry aneurysms. 10 types with varying inheritance. Type III collagen most affected (resulting in blood vessel instability)
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Osteogenesis imperfecta
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variety of gene defects all resulting in abnormal collagen synthesis. Most common form is autosomal dominant affecting type I collagen. Causes:
1. Multiple fractures with minimal trauma (brittle bone disease) which may occur during birth process 2. Blue sclerae due to translucency of connective tissue over choroid 3. hearing loss (abnormal middle ear bones) 4. dental imperfections Type II is fatal in utero. Incidence is 1:10,000 May be confused with child abuse |
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Elastin
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Stretchy protein in lungs, large arteries, elastic ligaments. Rich in proline and lysine. Tropoelastin with fibrillin scaffolding. Has relaxed and stretched confirmations. Elastase degrades, inhibited by a-antitrypsin. Excess elastase activity can cause emphysema (lungs lose recoil)
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Marfan's syndrome
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Caused by defect in fibrillin.
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Metabolism occurring only in the mitochondria
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Fatty acid B-oxidation, acetyl Co-A production, Krebs cycle
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Metabolism occurring only in the cytoplasm
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Glycolysis, fatty acid synthesis, HMP (pentose phosphate) shunt, protein synthesis (RER), steroid sythesis (SER)
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Metabolism occurring in both the mitochondria and the cytoplasm
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Gluconeogenesis, urea cycle, heme synthesis
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Hexokinase vs Glucokinase
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Hexokinase- all tissues. high affinity, low capacity. Feedback inhibition by glucose-6-phosphate
Glucokinase - liver only. Low affinity, high capacity. No feedback inhibition. Phosphorylates excess glucose (such as after a meal) to sequester it in the liver. |
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What is the rate limiting step in glycolysis? What is the enzyme involved, and what factors regulate its activity?
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Fructose-6-P --> Fructose-1,6-BP (irreversible)
Phosphofructokinase-1 is the enzyme involved. ATP and citrate inhibit, while AMP and Fructose-2,6-BP activate. Fructose-2,6-BP activation is the most potent of these regulators (overrides inhibition by ATP, citrate) |
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Why do glycolytic enzyme deficiencies lead to hemolytic anemia? What enzyme is the most common deficiency?
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RBC have no mitochondria (no aerobic glucose metabolism) and hence depend solely on glycolysis. Pyruvate kinase deficiency is implicated in 95% of cases.
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What is the reaction catalyzed by pyruvate kinase? What factors regulate its action?
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phosphoenolpyruvate --> pyruvate (irreversible). ATP and alanine are inhibitory, fructose-1,6-BP is activating.
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What enzyme catalyzes pyruvate-->Acetyl CoA (irreversible) and what regulates its actions?
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Pyruvate dehydrogenase, which is inhibited by ATP, NADH, and acetyl-CoA
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What cofactors are part of the pyruvate dehydrogenase complex? What other enzyme complex is it similar to?
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Vitamins B1, B2, B3, B5, and lipoic acid.
The complex is similar to a-ketoglutarate dehydrogenase complex which uses the same cofactors and has a similar substrate and action. |
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What is the overall reaction catalyzed by the pyruvate dehydrogenase complex? How does exercise active it? What poison inhibits it and how?
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pyruvate + NAD(+) + CoA --> acetyl-CoA + CO2 + NADH
exercise activates by increasing the NAD+/NADH ratio, increasing ADP, and increasing Ca++ in the cytoplasm. Arsenic inhibits lipoic acid, leading to vomiting, rice water stools, and garlic breath |
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What happens if there is a deficiency of pyruvate dehydrogenase?
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There is a backup of substrate (pyruvate and alanine) leading to lactic acidosis. The deficiency can be congenital or acquired (as in B1 deficiency). The primary finding is neurological defects.
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What is the treatment for pyruvate dehydrogenase deficiency?
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To increase the intake of ketogenic nutrients (ie high fat or high lysine and leucine -- only purely ketogenic AAs)
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