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168 Cards in this Set
- Front
- Back
Which histones form the nucleosome octamers that DNA loops around?
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H2A, H2B, H3, H4
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H1 ties nucleosomes together in a ___-nm string.
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30 nm
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Heterochromatin is ___ and transcriptionally ___.
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condensed, inactive
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Euchromatin is ___ and transcriptionally ___.
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loose, active
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Purines consist of ___ & ___, and have ___ ring(s)
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Adenine & Guanine; 2 rings
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Pyridimidines consist of ___, ___, & ___ and have ___ ring(s).
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Cytosine, Uracil, Thymine; 1 ring
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Guanine has a ___ group.
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ketone
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Thymine has a ___ group.
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methyl
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Nucleotides are linked by ___'-___' ___ bonds.
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3'-5' phosphodiesterase bond
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Silent mutation =
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same AA, often base change in 3rd position of codon
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Missense mutation =
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changed AA (new AA is similar in chemical structure)
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Nonsense mutation =
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early STOP codon
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Frame shift mutation =
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misreading of all downstream nucleotides, result in truncated protein (WORST damage!)
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DNA topoisomerases =
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create nick in helix to relieve supercoils
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Primase =
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makes RNA primer for DNA Pol III to start replication
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DNA Pol III =
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elongates DNA chain by adding nucleotides to 3' end; has 3'-5' exonuclease proofreading activity
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DNA Pol I =
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degrades RNA primer
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DNA ligase =
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seals
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DNA repair: ___ locates damaged base, ___ makes a break upstream, ___ removes the chunk of nucleotides, ___ fills gap, ___ seals.
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excision repair-specific glycosylase, endonuclease, exonuclease, DNA pol, DNA ligase
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DNA repair defects:
Xeroderma pigmentosum ~ ___ Ataxia-telangiectasia ~ ___ Bloom's syndrome ~ ___ Fanconi's anemia ~ ___ |
XP ~ UV light
AT ~ xray BS ~ radiation FA ~ crosslinking agents |
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Xeroderma pigmentosum is where you can't repair ___ ___ which form in DNA when exposed to UV light. Associated with ___ & ___.
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thymine dimers
dry skin, melanoma |
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mRNA is the ___ type of RNA.
rRNA is the ___ type of RNA. tRNA is the ___ type of RNA. |
largest
most abundant smallest |
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RNA Pol I makes ___.
RNa Pol II makes ___. RNA Pol III makes ___. |
rRNA
mRNA tRNA |
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alpha-amanitin (from mushrooms) inhibits RNA Pol ___.
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RNA Pol II --> cannot open DNA to start transcription
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Prokaryotic RNA Pol makes ___.
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all 3 kinds of RNA.
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Stop codons =
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UGA
UAA UAG |
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Promoter =
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site where RNA Pol and TFs bind DNA upstream from gene locus
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Enhancer =
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piece of DNA that alters a gene expression by binding TFs
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Operator =
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where gene repressors bind
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Exons =
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encode the actual genetic info
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After mRNA transcription, 3 processes:
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1) capping 5'end (7-methyl-G)
2) polyAAA tail 3) splice out introns * then transport out of nucleus |
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All tRNAs have _ _ _ at the 3' end which binds AA.
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CCA
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What is the enzyme that links an AA to the 3'end of tRNA?
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aminoacyl-tRNA synthase - 1 per AA, uses ATP
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What is tRNA wobble?
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mRNA codons differing in 3rd base position may still code for same tRNA/AA
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Methionine sits in the ___ site on the ribosome, the incoming AA lands in the ___ site.
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P site, A site
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How is GTP used in protein synthesis?
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"tRNA gripping & going places" - translocation along the ribosome
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___ Km = higher affinity
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lower
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Km =
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[S] at 1/2 Vmax
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Competitive inhibitors:
effect on Vmax = effect on Km = |
unchanged
increase |
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Noncompetitive inhibitors:
effect on Vmax = effect on Km = |
lower
unchanged |
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Most cells are in which phase?
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G0
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Rapidly dividing cells have a short ___ phase.
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G1
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How can enzymes be regulated?
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1) synthesis/destruction
2) zymogen cleavage 3) phosphorylation 4) feedback inhibition 5) transcriptional regulation |
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What happens in the RER?
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1) make secretory proteins
2) add N-linked oligosaccharide to proteins |
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What are Nissl bodies?
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neuronal RER that make enzymes and NTs (not found in axon hillock or axon)
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What happens in the SER?
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1) steroid synthesis
2) detox of drugs/poisons |
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Which cells have a lot of RER?
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goblet cells, plasma cells
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Which cells have a lot of SER?
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hepatocytes, adrenal cortex
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I-cell Disease =
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Caused by failure to add mannose-6-phosphate to lysosome proteins --> enzymes secreted out of cell instead of going to lysosome. Have coarse facial features and restricted joint movement.
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What are the 6 functions of Golgi?
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1) distribute proteins/lipids
2) modify N-oligosaccharides 3) add O-oligosaccharides 4) assemble proteoglycans 5) sulfation of sugars 6) add mannose-6-phosphate to lysosomal proteins which targets protein to lysosome |
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Drugs that act on microtubules:
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1) mebendazole/thiabendazole for worms
2) griseofulvin for fungi 3) taxols for breast cancer 4) vinca alkaloids for cancer 5) colchicine for gout |
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Chediak-Higashi syndrome =
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microtubule polymerization defect --> dec. phagocytosis
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Cilia structure =
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9 + 2 arrangement microtubules, dynein for retrograde axon transport, kinesin for anterograde axon transport
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Microtubules are found in what cell structures?
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flagella, cilia, mitotic spindles
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Kartagener's syndrome =
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dynein arm defect --> immotile cilia (infertility, chronic respiratory infection)
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What is the function of cholesterol in plasma membrane?
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promote stability, makes up ~ 50% of membrane
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Phosphatidylcholine =
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aka lecithin; component of RBC membrane, myelin, bile, surfactant (dipalmitoyl phosphatidylcholine); helps esterify cholesterol
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Na/K pump =
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3 Na out: 2 K in (1 ATP used)
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Oubain inhibits Na/K pump by:
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binding to K site
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Digoxin and digitoxin inhibit Na/K pump -->
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inc. heart contractility
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Gq goes to which receptors to activate phospholipase C?
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H1, a1, V1, M1, M3
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IP3 -->
DAG --> |
inc. intracellular calcium
protein kinase C |
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Gs subunit goes to which receptors to activiate adenylyl cyclase?
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B1, B2, D1, H2, V2
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Gi subunit goes to which receptor to inhibit adenylyl cyclase?
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M2, a2, D2
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Type 1 collagen found in:
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BONE, tendon, skin, fascia, teeth, cornea, late wound repair
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Type 2 collagen found in:
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CARTILAGE, vitreous body, nucleus pulposus
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Type 3 collagen found in:
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skin, vessels, uterus, fetal tissue, granulation tissue (early wound repair)
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Type 4 collagen found in:
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basement membrane
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Type 10 collagen found in:
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epiphyseal plate
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Preprocollagen =
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collagen alpha chains, Gly-X-Y (proline, lysine)
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Scurvy =
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VitC deficiency, cannot hydroxylate preprocollagen in ER
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Procollagen =
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triple helix of 3 alpha chains, made in Golgi
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Osteogenesis imperfecta =
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AD disorder, abnormal collagen synthesis at triple helix step --> multiple fractures, blue sclera, bad teeth, hearing loss
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Once triple helix procollagen get outside fibroblast:
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procollagen peptidases cleave terminal ends --> insoluble tropocollagen
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Ehlers-Danlos syndrome =
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faulty collagen synthesis at terminal cleavage step --> hyperextensible skin, hypermobile joints, easy bruising, associated with BERRY ANEURYSMS!
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Tropocollagen is crosslinked by ___ to make collagen fibrils.
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lysyl oxidase
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IHC stains:
vimentin desmin cytokeratin GFAP neurofilaments |
connective tissue
muscle epithelial cells neuroglia neurons |
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Metabolism sites: mitochondria
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1) fatty acid oxidation
2) acetyl CoA production 3) TCA cycle |
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Metabolism sites: cytoplasm
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1) glycolysis
2) fatty acid synthesis 3) HMP shunt 4) protein synthesis (RER) 5) steroid synthesis (SER) |
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Metabolism sites: both mito and cyto
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1) gluconeogenesis
2) urea cycle 3) heme synthesis |
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Aerobic metabolism of glucose yields ___ ATP via malate shuttle, ___ ATP via G3P shuttle.
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38, 36
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Anaerobic glycolysis yields ___ ATP per glucose.
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2
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Activated carriers: ready?
phosphoryl electrons acyl CO2 1-carbon units methyl groups aldehydes glucose choline |
ATP
NADH/NADPH/FADH2 coenzyme A, lipoamide biotin tetrahydrofolates SAM TPP UDP glucose CDP choline |
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ATP + methinonine =
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S-adenosyl methionine (methyl donor)
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Regeneration of methionine and SAM requires Vit__.
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B12
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Signal molecule precursors:
ATP --> GTP --> glutamate --> choline --> arachidonate --> fructose 6P --> 1,3 BPG --> |
cAMP
cGMP GABA Ach PGs, LTs, TX fructose 1,6 BP (via PFK) 2,3 BPG |
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NAD+ is generally used in catabolic or anabolic processes?
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catabolic, H+ away as NADH
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NADPH is used in ___ processes as a supply of reducing equivalents. It is a product of which pathway that takes place in cytoplasm?
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anabolic, HMP shunt
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NADPH needed for 3 things:
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1) anabolic processes
2) respiratory burst 3) P-450 |
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NADPH oxidase deficiency -->
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chronic granulomatous disease, cannot do first step in respiratory burst!
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Superoxide dismutase =
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turns O2- into H2O2
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Myeloperoxidase =
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turns H2O2 into HOCl (bleach), lyses phagocytosed bacteria!
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Catalase =
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converts H2O2 into water, and oxidizes GSH to GSSH
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Glutathione reductase =
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Duh. Reduces glutathione by oxidizing NADPH
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Glucose 6 phosphate dehydrogenase =
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makes NADPH, first step in HMP shunt (G6P to 6PG)
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Hexokinase is found ___.
Glucokinase is found ___. |
throughout body
in Liver |
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Glycolysis, irreversible enzymes (4):
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1) hexokinase/glucokinase
2) phosphofructokinase 3) pyruvate kinase 4) pyruvate dehydrogenase |
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Glycolytic enzyme deficiency -->
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hemolytic anemia, because RBC only use glucose anaerobically (no mito)
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Pyruvate dehydrogenase complex requires which 5 cofactors?
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1) pyrophosphate (B1/thiamine; TPP)
2) FAD (B2, riboflavin) 3) NAD (B3, niacin) 4) CoA (B5, pantothenate) 5) lipoic acid |
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What other complex uses the same cofactors as pyruvate dehydrogenase?
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a-ketoglutarate dehydrogenase
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Pyruvate dehydrogenase is activated by exercise which inc. 3 things:
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1) inc. NAD/NADH ratio
2) inc. ADP 3) inc. calcium |
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Reaction catalyzed by pyruvate dehydrogenase:
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pyruvate + NAD + CoA --> acetyl CoA + CO2 + NADH
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What happens in pyruvate dehydrogenase deficiency (vitamin def, alcoholism)?
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backup of pyruvate & ala --> lactic acidosis, neurologic defects!
* TX ~ eat ketogenic nutrients like fat or lys & leu |
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Which AA serves as a carrier of amino groups from muscle to liver?
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alanine
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2 functions of Oxaloacetate:
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1) TCA cycle (mito)
2) gluconeogenesis (mito & cytoplasm) |
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What catalyzes reaction of pyruvate --> lactate?
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Lactate Dehydrogenase (LDH)
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Which enzyme converts pyruvate --> Oxaloacetate?
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pyruvate carboxylase
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Which enzyme converts oxaloacetate --> PEP for gluconeogenesis?
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PEP carboxykinase
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What is the purpose of the Cori cycle?
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allows muscle to function anaerobically (net 2 ATP); muscle glucose --> pyruvate --> lactate which goes to Liver and is made into glucose again
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TCA cycle produces:
___ NADH ___ FADH2 ___ CO2 ___ GTP = ___ ATP |
3 NADH
1 FADH2 2 CO2 1 GTP = 12 ATP per acetyl CoA |
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What are the elements (in order) of the TCA cycle? Start after pyruvate --> acetyl CoA.
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acetyl CoA + oxaloacetate --> citrate --> isocitrate --> a-KG --> succinyl CoA --> succinate --> fumarate --> malate --> oxaloacetate
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Which ETC inhibitors directly inhibit electron transport, causing dec. proton gradient and block of ATP synthesis?
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rotenone, antimycin A, CN, CO
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Which is the ATPase inhibitor that directly inhibits mito ATPase, causing inc. proton gradient but no ATP production?
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oligomycin
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What is the uncoupling agent that inc. mito membrane permeability causing dec. proton gradient, continued O2 consumption, and no ATP production?
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2,4-dinitrophenol
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Gluconeogenesis, irreversible enzymes (w/o which leads to hypoglycemia):
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1) pyruvate carboxylase
2) PEP carboxykinase 3) fructose 1,6-BPase 4) glucose 6 phosphatase |
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Which organs can do gluconeogenesis?
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liver, kidney, intestine
* muscle cannot!! |
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What are the 2 functions of the HMP shunt (in cytoplasm)?
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1) make ribose-5P from glucose-6P for nucleotide synthesis
2) generate NADPH for FA synthesis, steroid synthesis, reducing glutathione |
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G6PD deficiency:
- what kind of anemia? - inheritance? - epidemiology? - intracellular body? |
- hemolytic anemia due to low NADPH in oxidative situations
- XR - blacks more - Heinz body (Hb precipitate) |
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Which oxidizing agents can precipitate a G6PD deficiency attack?
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- fava beans
- anti-TB drugs - sulfonamides - primaquine |
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What is the missing enzyme in fructose intolerance (AR dz)?
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aldolase B - accumulate fructose 1P causing dec. in available P and inhibit glycogenolysis & gluconeogenesis
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What is the defective enzyme in essential fructosuria?
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fructokinase - benign, asymptomatic, just fructose appears in blood/pee
|
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What is the absent enzyme in galactosemia (AR disease)?
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galactose-1P uridyltransferase - accumulate toxic substances causing mental retardation, hepatomegaly, cataracts!
* TX ~ don't eat lactose or galactose |
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Who gets lactase deficiency?
|
blacks, Asians
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Essential AA:
ketogenic (2)= glucogenic (5)= both (3)= |
Leu, Lys
Met, Thr, Val, Arg, His Ile, Phe, Trp |
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What are the si/sx of fructose intolerance?
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hypoglycemia, jaundice, cirrhosis, vomiting
* TX ~ don't eat fructose or sucrose! |
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Which 2 essential AA are required during periods of growth?
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Arg, His
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Which 2 basic, positively charged AA are found in histones because they bind to negatively charged DNA?
|
Arg, Lys
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At body pH 7.4, acidic AA glutamate and aspartate are ___ charged.
|
negatively
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Urea cycle:
CO2 + NH4 --> carbamoyl P... then what? |
carbamoyl P + ornithine --> citrulline, + aspartate --> argininosuccinate, - fumarate (join TCA cycle) --> arginine, + H2O --> UREA!
|
|
AA derivatives:
Phe --> |
tyrosine --> thyroxine, Dopa --> melanin, dopamine --> NE --> Epi
|
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AA derivatives:
Trp --> |
niacin --> NAD/NADP
serotonin melatonin |
|
AA derivatives:
His --> |
histamine (easy peasy)
|
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AA derivatives:
Gly --> |
porphyrin --> heme
|
|
AA derivatives:
Arg --> |
creatine
urea nitric oxide |
|
AA derivatives:
Glu --> |
GABA
|
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What is missing in Phenylketonuria?
|
either low phenylalanine hydroxylase, or low tetrahydrobiopterin cofactor - can't make Tyrosine
|
|
How does PKU present?
|
mental retardation, growth retardation, musty odor, fair skin, eczema
* AR disease, 1:10 000 * TX ~ lower Phe and raise Tyr in diet |
|
What disease makes urine turn black on standing and makes connective tissue dark? May have arthralgias but otherwise benign condition.
|
Alkaptonuria, deficiency of homogentisic acid oxidase in degradative pathway of Tyrosine
|
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What are the causes of albinism?
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1) no tyrosinase - can't make melanin from Tyr
2) defective Tyr transporters |
|
What are 3 forms of homocystinuria?
|
1) cystathionine sythase def.
2) dec. affinity of cystathionine synthase for B6 3) methionine synthase def. |
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What are the si/sx of homocystinuria?
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mental retardation, tall stature, osteoporosis, kyphosis, lens subluxation, atherosclerosis
|
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Which AA transporters are missing from kidney tubules in the disease Cystinuria?
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COLA - cysteine, ornithine, lysine, arginine
|
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What is a result of cystinuria?
|
Cystine kidney stones, TX acetazolamide to alkalinize urine
|
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What is the disease where you can't degrade branched AA (Ile, Leu, Val)?
|
Maple Syrup Urine disease - deficient a-ketoacid dehydrogenase lead to inc. Leu in blood
|
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How can Maple Syrup Urine disease present?
|
severe CNS defects, mental retardation, death
|
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What happens if there is deficient Adenosine deaminase?
|
Build up ATP and dATP --> inhibit ribonucleotide reductase --> prevent DNA synthesis and lymphocyte production --> SCID!!
|
|
What is the enzyme missing in Lesch-Nyan syndrome?
|
HGPRTase, which converts hypoxanthine to IMP and guanine to GMP
|
|
What are some manifestations of Lesch-Nyan syndrome?
|
- hyperuricemia, gout
- retardation - self-mutilation, aggression |
|
In fasted state, Liver glycogen will eventually become ___ and ___.
|
glucose (via G6P --> glu), ketones (via G6P --> pyruvate --> acetyl CoA)
|
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Insulin is needed for glucose uptake in ___ and ___.
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skeletal muscle, adipose
|
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GLUT 2 receptors are found:
|
beta cells
|
|
GLUT 4 receptors are found:
|
muscle and fat
|
|
5 anabolic effects of insulin:
|
1) glucose uptake
2) glycogen synthesis 3) TG synthesis 4) Na retention in kidney 5) protein synthesis in muscle |
|
Glucagon turns glycogen synthase ___, glycogen phosphorylase ___.
|
OFF, ON
|
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Insulin turns glycogen synthase ___, glycogen phosphorylase ___.
|
ON, OFF
|
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Von Gierke's disease =
|
glucose 6-phosphatase deficiency; hypoglycemia, hepatomegaly, inc. blood lactate
|
|
Pompe's disease =
|
lysosomal a-1,4 glucosidase deficiency; cardiomegaly, hepatomegaly, lack muscle tone or weakness (ie exercise intolerance, difficulty breathing)
|
|
Cori's disease =
|
lysosomal a-1,6 glucosidase; mild hypoglycemia, normal lactate
|
|
McArdle's disease =
|
skeletal muscle glycogen phosphorylase deficiency; can't break down glycogen; get cramps and myoglobinuria upon exercising
|
|
Tay-Sach's disease:
inheritance enzyme accumulated substrate findings |
AR
hexosaminidase A GM2 ganglioside progressive neurodegeneration, developmental delay, cherry red spot, onion skin lysosomes |
|
Fabry's disease:
inheritance enzyme accumulated substrate findings |
XR
a-galactosidase A ceremide trihexoside peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease |
|
Gaucher's disease:
inheritance enzyme accumulated substrate findings |
AR
beta-glucocerebrosidase glucocerebroside hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gauchers cells (macs) |
|
Niemann-Pick disease:
inheritance enzyme accumulated substrate findings |
AR
sphingomyelinase sphingomyelin progressive neurodegeneration, hepatosplenomegaly, cherry red spot |
|
Krabbe's disease:
inheritance enzyme accumulated substrate findings |
AR
beta-galactosidase galactocerebroside peripheral neuropathy, developmental delay, optic atropy |
|
Metachromatic Leukodystrophy:
inheritance enzyme accumulated substrate findings |
AR
arylsulfatase A cerebroside sulfate central and peripheral demyelination w/ataxia, dementia |
|
Hurler's syndrome:
inheritance enzyme accumulated substrate findings |
AR
a-L-iduronidase heparan sulfate, dermatan sulfate developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly |
|
Hunter's syndrome:
inheritance enzyme accumulated substrate findings |
XR
iduronate sulfatase heparan sulfate, dermatan sulfate mild Hurler's + aggressive behavior, no corneal clouding |
|
What are si/sx of Fanconi's anemia?
|
AR disease of DNA repair defect, pancytopenia, cafe au lait spots, short stature, radial arm deformities (no thumbs), small testicles, small head, mental retardation, small kidneys
|