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162 Cards in this Set
- Front
- Back
Histone octamer
|
2 each:
H2A H2B H3 H4 H1 = only histone not in nucleosome core - ties nucleosomes together in a string Heterochromatin = CONDENSED/inactive Euchromatin = LESS CONDENSED/active |
|
AA's used in purine synthesis
|
Glycine
Aspartate Glutamine |
|
Purines
|
A, G = Pure As Gold
CO2 Glycine 2 N10-formyl-tetrahydrofolate Glutamine Aspartate |
|
Pyrimidine
|
C, T, U
(deamination of C --> U) Carbamoyl phosphate Aspartate |
|
Gibbs Free Energy
|
direction of chemical reaction at equilbirium
G = -RTlnK G = (-) so K>1 = products > reactants G = (+) so K<1 = reactants > products If K = 1 , then G = 0 |
|
Transition
|
Substitute purine for purine or pyrimidine for pyrimidine
|
|
Transversion
|
Purine for pyrimidine or V-V
|
|
DNA Replication Enzymes
|
Helicase - unwinds DNA at replication fork
SSBPs - prevent strands from reannealing DNA topoisomerase - nick in helix to relieve supercoils during replication Primase - make RNA primer that DNAPolIII uses to initiate replication |
|
DNA Replication Enzymes
|
DNA Poymerase III
- PROKARYOTIC only - elongate by adding to 3' end (5 to 3' synth) - elongate lagging strand until reach primer of preceding fragment - 3-5' proofreading exonuclease DNA Polymerase I - PROKARYOTIC ONLY - degrade RNA primer --> fill in gap w/ DNA - 5'-3' exonuclease activity DNA ligase = sealer |
|
Nucleotide excision repair
|
Specific ENDONUCLEASES release oligonucleutodie-containing damaged base
DNA pol + ligase fill and reseal gap MUTATED IN XERODERMA PIGMENTOSA |
|
Base Excision Repair
|
GLYCOSYLASES recognize and remove damaged bases
Endonuclease cut DNA at APYRIMIDINIC site Gap filled & resealed Order: 1. Glycosylase 2. Endonuclease 3. Lyase 4. DNA Pol 5. Ligase |
|
Mismatch repair
|
UNMETHYLATED newly synth strand recognized
MUTATED in HNPCC |
|
Other inherited disorders caused by defic DNA repair enzymes:
|
1. Ataxia telengiectasia
2. Fanconi anemia |
|
mRNA start codons
|
AUG:
Euk = methionine Prok = f-met |
|
Polycistronic
|
Bacterial mRNA
ex. lac operon |
|
Kozak sequence
|
EUK mRNA
AUG positioned near Kozak sequence --> intitation of translation |
|
Homeobox
|
Highly conserved DNA sequence (180 nucleotides)
Code for DNA-binding trancription factors (alter exp of genes involved in morphogenesis) |
|
Promoter
|
RNA polymerase and TF's bind to DNA upstread from gene locus
AT -rich w/ TATA & CAAT boxes |
|
Enhancer/Silencer
|
Located close/far away/within gene whose expression it regulates
|
|
EUK RNA Polymerase
|
RNA Pol 1 = rRNA
RNA Pol 2 = mRNA - inhib by alpha-amanitin (mushrooms) RNA Pol 3 = tRNA NO PROOFREADING |
|
PROK RNA Polymerase
|
1 RNA Pol = makes all 3 kinds of RNA
|
|
RNA EUK processing
|
Initial unprocessed transcript = hnRNA
Capped + tailed transcript = mRNA - this is the only kind transported OUT of nucleus AAUAAA = polyadenylation signal (does not require template) |
|
Splicing pre mRNA
|
transcript + snRNPs --> splicesome
Remove intron --> join 2 exons ** mutation in splice sites: produce larger proteins w/ altered fxn but preserved immune activity ** Different exons can be combined via ALTERNATIVE SPLICING --> B-thalessemia mutations |
|
2 types Enzyme linked receptors
|
1. w/ Intrinsic enzyme activity
- signaling via MAP kinase, autophosphorylation --> phosph Ras ex. EGF, PDGF, FGF 2. w/out intrinsic enzyme activity - JAK/STAT - ex. cytokines, GH, prolatctin, IL-2 |
|
30S subunit
|
Attaches aminoacyl-tRNA
Inhib by tetracyclines contains 16S rRNA = essential for init of protein synthesis - express sequences COMPLIMENTARY to shine-dalgarno in mRNA - allow mRNA + 30S to bind for protein translation |
|
Translation energy requirements
|
tRNA aminoacetylation : ATP --> AMP
- 2 phosphoanhydride bonds Loading tRNA onto ribosome: GTP --> GDP Translocation: GTP --> GDP Total energy: 4 high energy phosphoanhydride bonds |
|
Proteasomal degradation
|
UBIQUITIN attachment to defective proteins to tag them for breakdown
|
|
mtDNA
|
maternally derived from oocyte
37 genes - 13 proteins - 2 forms rRNA - 22 forms tRNA non nuclear location |
|
Cell cycle regulation
|
CDK - constitutive and inactive
Cyclins - reg proteins that control cell cycle events; PHASE SPECIFIC; activate CDKs G1-S progression: regulated by Rb + p53 |
|
Cell types
|
Permanent = stay in Go
- neurons - skel/cardiac muscle - RBCs Stable = Go-->G1 - hepatocytes - lymphocytes Labile = Never go to Go, divide rapidly w/ short G1 - BM, gut epithelium, skin, hair |
|
Smooth ER
|
loc in:
- liver hepatocytes - adrenal cortex |
|
Golgi apparatus
|
1. Protein/lipid distribution from ER to
- plasma membrane - lysosomes - secretory vessicles 2. Modify N-oligo on Asp 3. Add O-oligo to Ser, Thr 4. Add mannose-6P --> lysosome target 5. Proteoglycan assembly from core protein 6. Sugar sulfation |
|
Trafficking proteins
|
COPI
- retrograde Golgi --> ER COPII - anterograde RER --> cisGolgi Clathrin trans-Golgi --> lysosomes, plasma membrane --> endosomes |
|
Microtubule
|
polymerized alpha+beta tubulin dimers w/ 2 bound GTP
Motor proteins: 1. Dynein = RETROgrade (+-->-) 2. Kinesin = ANTEROgrade (- to +) |
|
Cilia
|
9+2 microtubule arrangement
Anoxenaml dyein = ATPase linking peripheral 9 doublets - cause cilium bending by differential sliding |
|
Immunohistochemical stains
|
Vimentin = CT
Desmin = MUSCLE Cytokeratin = epithelial cells GFAP = neuroglia Neurofilamets = Neuron |
|
Sodium pump
|
Na/K ATPase on plasma membrane
ATP on cytoplasmic side 1 ATP --> 3Na+ OUT / 2K+ IN |
|
TYpe I Collagen
|
bone
skin tendon dentin fascia, cornea late wound repair |
|
Type II Collagen
|
Cartilage (hyaline)
vitreous body nucleus pulposes |
|
Type III collagen
|
Reticulin
skin BV's uterus fetal tissue granulation tissue |
|
Type IV Collagen
|
Basement membrane
|
|
Collagen synth/structure
|
2 stages:
1. In fibroblasts 2. Out of fibroblasts |
|
In fibroblast:
|
1. Synthesis = PREPROcollagen
- RER - alpha-collagen translation --> Gly-X-Y polypeptide (X, Y = proline/OHproline/OHlysine) 2. Hydroxlyation - ER - hydroxylation of proline, lysine * REQUIRES VIT C --> Scurvy 3. Glycosylation - ER - form PROcollagen = triple helix - Osteogen Imperfecta 4. Exocytosis |
|
Outside fibroblast:
|
4. Proteolytic processing
- INSOLUBULE TROPOcollagen - Ehlers Danlos 6. X-linking - via lysyl oxidase --> COLLAGEN FIBRILS |
|
Ehlers Danlos
|
Faulty collagen synthesis of type III
1. hyperextensible skin 2. tendency to bleed = easy bruising 3. hypermobile joints AD/AR assoc w/ joint location, berry aneurysms, organ rupture |
|
OI
|
Brittle bone dz
AD Type I collagen Multiple birth fractures Blue sclerae Hearing loss Dental problems TYPE II IS FATAL IN UTERO |
|
Elastin
|
Broken down by elastase
- usu inhib by a1-antitrypsin (emphysema) Marfan's - fibrillin defect |
|
Southern Blot
|
SNoW DRoP
DNA electrophoresed on gel --> filter Labeled DNA probe --> anneal Visualize dsDNA on film |
|
Northern Blot
|
RNA sample
|
|
Western blot
|
Sampe PROTEIN separated via gel electrophoresis
Labeled antibody used to bind relevant protein |
|
Microarray
|
thousands nucleic acid sequenecs arranged in grids
DNA /RNA probes hybridized to chip --> detect relative amounts of copmlimentary binding PRofile gene expression or detect SNPs |
|
ELISA
|
Immunologic technique - test for Ab/Ag reactivity
Intense color reaction = (+) result via peroxidase enzyme - ex. HIV test |
|
FISH
|
Fluorescent DNA/RNA probe binds to specific gene site of interest
- use for specific localization of genes and direct visualization of anomalies at molecular level Fluorescen = gene present No fluorescence = gene deleted |
|
Cloning
|
DNA frag inserted into bacterial PLASMID w/ antibiotic resistance genes
Restriction enzymes allow insertion of fragment into plasmid Tissue mRNA isolated and exposed to reverse transcriptase --> cDNA (NO INTRONS) library |
|
Sanger DNA Seq
|
dideoxynucleotides halt DNA polymerase at each base --> sequences of diff lengths
- deduce original sequence |
|
Transgenic studies in mice
|
Constitutive - random insertion of gene into mouse genome
Conditional - homologous recombination Manipulate gene at specific developmental point w/ inducible Cre-lox system with antibiotic controlled promoter (study gene whose deletion causes lethal embryonic) |
|
RNAi
|
dsRNA synth complementary to mRNA seq of interest
Transfect human cells --> dsRNA separate --> promote degradation of target mRNA -- knock out gene expression |
|
Change in 2nd gen?
|
No w/ phenotypic mixing and transformation
Yes w/ reassortment and recombination |
|
Dominant negative mutation
|
heterozygote produces nonfunctional altered protein that also prevents normal gene product from functioning
|
|
Linkage disequilibrium
|
Tendency for certain alleles @ 2 linked loci to occur together more often than expected by chance
- measured in a pop - not in a family - often varies in diff pop's |
|
Mosaicism
|
Mut's at diff loci can produce the same phenotype
ex. McCune Albright syndrome |
|
Locus heterogeniety
|
Mutations at different loci can produce same phenotype
ex. albinism |
|
Heteroplasmy
|
normal and mutated mtDNA --> variable expression of mitochondrial inherited dz's
|
|
H-W genetics
|
p and q = separate alleles in a pop; assumes
1. no mutations @ locus 2. No selection for any of the genotypes 3. Random mating & no migration Dz prev = p^2 + 2pq + q^2 = 1 Allele prev = p+q = 1 2pq = heterozygote prevalence Prev of XR dz in males = q in females = q^2 |
|
Imprinting
|
chr15
only 1 allele is active, other is inactive via methylation deletion of active allele --> dz - can also be from uniparental disomy PW syndrome - del of paternal allele angelmanns' - del of maternal allele |
|
Hypophosphatemic Rickets
|
X-linked D
Inc. phosphate wasting at prox tubule Rickets-like presentation |
|
Mitochondrial dz's
|
1. Leber hereditary optic neuropathy
-BL vision loss 2. Myoclonic epilepsy w/ RRF 3. Mito encephalomyopathy - MELAS - lactic acidosis + stroke like episodes |
|
AD dz's
|
Achondroplasia
ADPCKD FAP Famililal hypercholesterolemia (typeIIA) Hereditary hemorrahgic telengiectasia (Osler-Weber-Rendu sndrome) Hered spherocytosis Huntington's |
|
AD dz's continued
|
Marfan's
MEN NF I/II Tuberous sclerosis VHL dz |
|
AR dz
|
Albinism
ARPCKD CF Glycogen storage dz's Hemochromatosis Mucopolysaccharidoses (except Hunter's) Phenylketonuria Sickle cell Sphingolipodoses (except Fabry's) Thalassemias |
|
CF
|
Chr 7 , CFTR gene
Nl channel - actively secrete Cl- in lungs & GI tract, actively reabsorb Cl- from sweat Defective channel - thick mucus plugs --> plug lungs/pancreas/liver, recurrent pulm infec (Pseudomonas, S. aureus) - malabsorption (ADEK) + steatorrhea - meconium ileus (newoborns) Dx: inc [Cl] in sweat Tx: Nacetylcysteine to loosen plugs |
|
XR disorders
|
Bruton's agammaglobulinemia
Wiskott Aldrich Fragile X G6PD Duchenne's (and Becker) Muscular dystrophy Hemophilia A/B Fabry's dz Hunter's |
|
Trinucleotide repeat disorders
|
Huntington's
Myotonic dystrophy Fragile X Friedrich's ataxia * may demonstrate genetic anticipation |
|
Results of Down's pregnancy quad screen
|
dec AFP, estriol
inc B-hCG inc inhibin A Ultrasound - inc nuchal translucency |
|
Roberstonian translocation
|
NONRECIPROCAL chr translocation
- seen in 13, 14, 15, 21, 22 - result in miscarriage, stillbirth, chr imbalance (ex. down's/patau) |
|
Pericentric chr inversion
|
involves centromere
proceeds through meisosi |
|
Paracentric chr inversion
|
Does not involve centromere
Does not proceed through meisosi |
|
Vit A
|
retinol
antioxidant, visual pigments def: night blindness/dry skin Acute OD: N/V, vertigo, blurred vison Chronic OD: alopecia, dry skin, visual difficulties, hyperlipidemia, hepatotoxicity, hepatosplenomegaly |
|
Vit B1 = thiamine
|
TPP
cofactor for : 1. pyruvate dehydrogenase = glycolysis 2. a-KG dehydrogenase = TCA 3. Transketolase = HMP shunt 4. Branched chain AA dehydrogenase Def: Wernicke-Korsakoff syndrome, beriberi (dry - polyneuritis, symm muscle wasting; wet - high output cardiac failure, edema) |
|
Vit B2
|
riboflavin, FADH2 (FAD, FMN = 2ATP)
cofactor in ox/red Def: cheilosis, corneal vascularization |
|
Vit B3
|
niacin, NAD/NADP (=3 ATP)
derived from TRYPTOPHAN req B6 for synth Def: glossitis pellagra (Hartnup dz - dec tryptophan absorption) carcinoid syndrome (inc trytophan metab) INH (dec B6) excess: FACIAL FLUSHING!! (tx for hyperlipidemia) * high NADH + hypoglycemia = fuel other than glucose being used |
|
B5
|
pantothenate
CoA cofactor for acyl transfers + fatty acid synthase Def: dermatitis, enteritis, alopecia, adrenal insufficiency |
|
B6
|
pyridoxine
cofactor in transamination (ALT/AST), decarboxylation, glycogen phosphoyrlase, heme synth - req for niacin synth from tryptophan Def: convulsions, hyperirritability, periph neuropathy (INH) |
|
VitB12
|
cobalamin
cofactor for homocysteine methyltransferase synth only by microorg's - very large storage pool in liver req for: homocyst + CH3THF --> met + THF methylmalonylCoA --> succinylCoA (note this is an isomerization rxn) |
|
SAM
|
s-adenosyl-methionine
transfers methyl units regenerates methionine - dep on B12 + folate |
|
Biotin
|
cofactor for carboxylation enzymes
1. pyruvate carboxylase 2. acetylcoA carboxylase (FA synth) 3. propionyl CoA carboxylase (OC FA catabolism) |
|
Vit C
|
antioxidant
1. facil Fe2+ absorption by keeping it in reduced state (absorbable form) 2. Necess for hydroxylation of proline/lysine in collagen synth 3. DA B-hydroxylase (DA--NE) scurvy - swollen gums/bruising/anemia/poor wound healing |
|
Excess VitD
|
seen in sarcoidosis (inc activ of VitD by epithelioid macrophages)
|
|
VitE
|
antioxidant
- protects erythrocytes and membranes from radical free damage def: inc fragility of erythrocytes (hemolytic anemia), muscle weakness, neurodysfxn |
|
Ethanol metabolism
|
NAD+ = limiting reagent!!
Alcohol dehydrogenase: CYTOSOL (NAD-->NADH), zero order kinetics ethanol --> Acetaldehyde Acetaldehyde dehydrogenase: MITO (NAD --> NADH) Acetaldehyde --> Acetate high NADH/NAD ratio favors: 1. Pyruvate --> Lactate 2. OAA --> Malate - alchol induced hyopglycemia (inhib gluconeogen and stim FA synth --> hepatic fatty change) |
|
Kwashiorkor v. Marasmus
|
Kwash = protein malnutrition, edema, liver malfxn - swollen belly
marasmus = energy malnut resulting in tissue/muscle wasting |
|
Mitochondria Rxns
|
Fatty acid oxid (B-oxid)
Acetyl CoA prod TCA cycle Oxidative phosphorylation |
|
Cytoplasm rxns
|
Glycolysis
FA synth HMP shunt Protein synth (RER) Steroid synth (SER) |
|
BOTH
|
Heme synth
Urea cycle Gluconeogenesis |
|
Glycolysis/ATP prod
|
Aerobic glucose metab
- malate aspartate shuttle (heart/liver) = 32 ATP - glycerol-3-phosphate shuttle (muscle)= 30ATP Anaerobic glycolysis: 2 net ATP/glucose |
|
Glucokinase
|
Loc in liver + pancreas; req ATP
Glucose sensor in B-cells; allows liver to serve as blood glucose buffer - high Km, high Vmax (v. hexokinase) - defect? leads to maturity onset diabetes - mutations --> dec glucose metabolism and dec insulin secretion |
|
Glycolytic enzyme defic
|
HEMOLYTIC ANEMIA
inability to maintain Na/K ATPase --> RBC swelling + lysis - b/c RBC metabolize glucose anaerobically (no mito) and thus depend solely on glycolysis def in Pyruvate kinase Phosphoglucose isomerase etc |
|
Pyruvate dehydrogenase
|
pyruvate + NAD --> acetyl CoA + Co2 + NADH
3 enzymes, 5 cofactors 1. TPP 2. FAD 3. NAD 4. CoA 5. Lipoc acid - inhib by arsenic Similar complex to alpha-KG complex |
|
Pyruvate dehydrogenase complex
|
- back up of pyruvate and alanine --> lactic acidosis
- congen/acq (B1 defic in alcoholics) neuro defects tx: inc intake of ketogenic nutrients (lys/leuc or high fat content) |
|
Cori Cycle
|
Lactate generated from ANAEROBIC metab --> hepatic gluconeogen --> source of glucose for muscle/RBCs
- cost: 4 ATP / cycle shifts metabolic burden to LIVER |
|
TCA Cycle
|
Produce: 12 ATP / acetyl CoA (2x everything per glucose)
3 NADH 1 FADH2 2 CO2 1GTP (substrate level phosphorylation) Citrate Is Kreb's Starting Substrate for Making Oxaloacetate |
|
Electron Transport Chain/Oxid Phosphorylation
|
NADH electrons from:
1. Glycolysis 2. TCA cycle - enter mito via : 1. Malate aspartate shuttle 2. Glycerol-3-phosphate shuttle ** FADH2 electrons transferred to complex II (lower energy than NADH) ATP synthase: 1 NADH = 3 ATP 1 FADH2 = 2 ATP |
|
Oxid phosphorylation poison
|
Rotenone/CN/antimycin A /CO
- electron transport inhibitors - dec proton gradient --> block ATP synth Oligomycin - ATPase inhibitors - inhib mitochondrial ATPase --> inc proton gradient 2,4,DNP , aspirin, thermogenin - inc mem perm --> dec prot gradient, inc O2 consumption - electron transport CONTINUES but ATP synth stops |
|
Irrev gluconeogen enzymes
|
primarily in liver
def of these enzymes --> hypoglycemia 1. Pyruvate carboxylase 2. PEP carboxykinase 3. F1,6,bisphosphatase 4. G6phosphatase |
|
Odd Chain Fatty ACid
|
Yield 1 propionyl-CoA during metabolism --> enter TCA cycle --> gluconeogenisis --> glucose source
** EVEN CHAIN can't do this because they only yield acetyl-CoA equiv's |
|
Pentose Phosphate Pathway = HMP shunt
|
Produces NADPH!!
- req for FA and steroid biosyth, glutathione red inside RBCs - 2 distinct phases (oxid/nonoxid) in CYTOPLASM - NO ATP USED/PRODUCED Sites: Lactating mammary glands/liver/adrenal cortex/RBCs |
|
Oxidative
|
IRREVERSIBLE
G6P dehydrogenase - rate limiting step - produces NADPH (immune response --> rapid release of reactive oxygen species; necess to keep glutathione reduced to detoxify free radicals and peroxides - if dec --> hemolytic anemia, XR) |
|
Nonoxidative
|
Transketolase
- req B1 - prod Ribose-5-phosphate, G3P, F6P |
|
Fructose metabolism
|
Note that fructose bypasses major regulatory steps in glycolysis
- mannose and galactose enter glycolysis prior to this step and therefore - these are all monosac's FRUCTOSE HAS HIGHEST RATE OF METABOLISM |
|
Fructose intolerance
|
Hered defic of ALDOLASE B
- AR - F1P accumulates --> dec available phosphate --> inhib of glycogenolysis + gluconeogen - sx's : hypoglycemia, jaundice, cirrhosis, vomiting - tx: decrease intake of both frucotse and sucrose |
|
Essential fructosuria
|
DEFECT IN FRUCTOKINASE
- AR - benign, asympt b/c fructose never enters cell at this point - sx's fructose in blood/urine |
|
Classic galactosemia
|
no Galactose-1-phosphoate uridyltransferase
- AR - accum of toxic substances (galctitol --> cataracts) - FTT , jaundice, hepatomegaly, infantile cataracts, MR - tx: exclude galactose/lactose from diet |
|
Galactokinase defic
|
Defic of galactokinase
- Mild - AR - sxs: galactose in blood/urine, infantile cataracts |
|
2* Lactase deficiency
|
assoc w/ small intest dz (celiac sprue/viral gastroenteritis)
|
|
Glucogenic AA's
|
Met
Val Arg - in histones to bind neg DNA His (used in gluconeogenesis) |
|
GlucogenicKetogenicAA
|
Ile
Phe Thr Trp |
|
Ketogenic AA
|
Leu
Lys - in histone to bind neg DNA |
|
Acidic AA
|
Asp and Glu
(neg charged @ body pH) |
|
Basic AA
|
Arg - most basic
Lys His - no charge at body pH |
|
Urea Cycle
|
AA catabolism
Excess nitrogen generated (ammonia + aspartate) --> converted to UREA --> excreted by kidney Ordinarily Careless Crapers Are Also Frivolous About Urination Ornithine Citrulline Argininosuccinate Fumarate (released) Arginine Urea |
|
Transport of ammonium
|
Via:
Alanine Glutamine From muscle --> liver for urea cycle |
|
Hyperammonemia
|
Acquired (liver dz) OR hereditary (urea cycle enzyme defic)
- excess NH4+ (depletes alpha-KG) --> inhib of TCA cycle ammonia intoxication: tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision tx: benzoate/phenylbutyrate to lower serum ammonia levels |
|
Arginase deficiency
|
Prog spastic paresis of LE's + choreoathetoid movements
- inc arginine levels in plasma + CSF |
|
Phenylalanine
|
Tyrosine (req BH4 for prod)
Tyrosine hydroxylase + BH4 : Dopa + Thyroxine Dopa decarboxylase : Dopamine, Melanin Dopamine B-hydroxylase: NE PNMT: Epi - controlled by cortisol |
|
Hartnup Dz
|
Def intestinal/renal absorption of tryptophan (dietary loss)
Clinical sx's: niacin def sx's |
|
Tryptophan
|
Niacin --> NAD+/NADP
Serotonin --> Melatonin |
|
Histidine
|
Histamine
|
|
Glycine
|
Porphyrin --> Heme
|
|
Arginine
|
Creatine
Urea NO |
|
Glutamate
|
GABA (req B6)
Glutathione |
|
BH4
|
Tetrahydrobiopterin
cofactor in synth of: tyrosine dopa serotonin NO Dihydrobiopterin reductase: BH2 --> BH4 (cyclical) - defic most common cause for BH4 defic |
|
Adenosine deaminase deficiency
|
excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribunonucleotide reductase
- prev DNA synth and thus dec lymphocyte count - causes SCID |
|
Lesch Nyhan syndrome
|
defective purine SALVAGE
- absence of HGPRT (hypoxanthine --> IMP; guanine --> GMP) - excess uric acid production sx's: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis |
|
Insulin resistance
|
aberrant serine + threonine residue phosphorylation by serine kinase
Occurs in presence of: TNF-alpha catecholamines glucocorticoids glucagon |
|
Glycogen
|
Branches: alpha-1,6-bonds
Linkages: alpha-1,4-bonds MUSCLE CAN'T release glucose into circulation b/c lacks glucose-6-phosphatase!! Liver CAN. Muscle: Ca2+ release from SR --> cytoplasm; binds tropnonin C --> muscle contraction and activate glcogen phosphorylase |
|
Limit dextans
|
4 glucose residues in branched configuration
|
|
Lysosomal degradation
|
Small amount of glycogen degraded in lysosomes by alph1,4 glucosidase --> glucose
|
|
FA synthesis
|
Acetyl CoA via CITRATE SHUTTLE --> malonyl CoA --> FA
|
|
FA degradation
|
= B-oxidation - sequential removal of 2C units from FA chain
Fatty acid CoA synthetase: FA + CoA --> AcylCoA CARNITINE SHUTTLE - inhib by malonyl CoA - carnitine def: inability to utilize LCFA's and toxic accumulation - yields Acyl-CoA (B-oxidation) --> breakdown to acetyl-CoA groups: ketone bodies, TCA cycle Acyl CoA dehydrogenase defic: - inc dicarboxylic acids - dec glucose and ketones |
|
Ketone bodies
|
made from HMG CoA
- metab by brain to 2 acetylCoA - excreted in urine (can't detect B-hydroxybutyrate in urine) made in 1. prolonged starvation/DKA 2. alcoholism |
|
Eicosanoids
|
Arach acid = precursor to 3 families
1. COX 1,2 - prostaglandins, thromboxanes - PGD2, PGE2, PGF2, PGI2, TXA2 2. 5-lipoxygenase - leukotriennes - 5HETE, LTB4, LTC4,D4,E4 3. 1,2, lipoxygenase - lipoxins - lipoxinA4, B4 (inhib neutrophil chemotaxis) |
|
Pancreatic lipase
|
degrade dietary TG in small intestine
|
|
Lipoprotein lipase
|
degrade TG circulating in chylomicrons and VLDLs
cofactor: CII |
|
Hepatic TG lipase
|
degradation of TG remaining in IDL
|
|
Hormone sensitive lipase
|
degradation of TG in adipocytes
|
|
LCAT
|
lecithin-cholesterol acyltransferase
- Nascent HDL --> Mature HDL - cataylizes esterification of cholesterol - activ by A1 |
|
CETP
|
cholesterol ester transfer protein
- mediate transfer of cholesterol esters to other lipoprotein particles |
|
B100
|
bind to LDL receptor
mediate VLDL secretion |
|
B48
|
mediate chylomicron secretion
|
|
E
|
mediate extra remnant uptake
|
|
Chylomicron
|
deliver dietary TG to periph tissue
deliver cholesterol to liver secreted by intest epithelial cells Apolipoproteins: B48 AIV, CII, E |
|
VLDL
|
deliver hepatic TG to periph tissue
secreted by liver B100 CII E |
|
IDL
|
degradation of VLDL
Deliever TGs and cholesterol to liver degraded to LDL B100, E |
|
LDL
|
deliver hepatic chol to periph tissue
formed by lipoprotein lipase modification of VLDL in periph tissue taken up by target cells via receptor-mediated endocytosis B100 |
|
HDL
|
mediate reverse cholesterol transport from periphery to liver
repository for ApoC and ApoE (needed for chylomicron + VLDL metab) secreted from liver + intestine |
|
Type I: Hyperchylomicronemia
|
Inc chylomicrons
Inc TG, cholesterol Lipoprotein lipase defic OR altered apolipoprotein CII |
|
Type II: Familial hypercholesterolemia
|
Inc LDL
Inc cholesterol AD Absent/dec LDL receptors |
|
Type IV: hypertriglyceridemia
|
Inc VLDL
Inc TG hepatic overproduction of VLDL |
|
Abetalipoproteinema
|
AR
hered inability to synth lipoproteins defic of apoB100 and apoB48 sx's appear in first few months of life - FTT, steatorrhea, acanthocytosis, ataxia, night blindness |
|
Type III: hyperlipoproteinemia
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xanthomas, premature coronary artery and peripheral vasc dz
1* defects in ApoE3/4 on chylomicrons and VLDL |
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lac operon in E. coli
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lac Z --> B-glucosidase (lactose --> glucose & galactose)
lac Y --> permease (allows lactose to enter bacterium) lac I --> repressor protein - binds to operator --> prev binding of RNA Pol OR inducer (lactose) causes conf. change preventing repressor from binding operator regulated by 2 distinct mechanisms: 1. negatively by binding of repressor protein to operator region 2. (+) by cAMP-CAP binding |
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lac operon in E. coli
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mut of repressor protein/binding site @ operator region --> prevents repression of genes of lac operon
- constitutive transcription of lac operon genes even in presence of glucose mutations of activator binding site/promoter/activator protein geine - prevent cAMP dependence upreg of gene |