Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
247 Cards in this Set
- Front
- Back
|
Anti-Tumoral Drugs Purine pathway |
Methotrexate: Dyhydrofolate reductase 5- Fluoracil: Thymidylate Synthase Hydroxyurea: Ribonucleotide reductase 6- Mercaptopurine: Block novo purine synthesis |
|
|
Antibiotics Purine pathway |
Trimethoprim: bacterial difydrofolate reductase |
|
|
Histones |
Octamere H2a, H2b,H3,H4 x2 (nucleosome core) form 10nm fibers H1-> 30 nm fibers |
|
|
Nucleotides |
Purines (Pure as gold) with two rings Adenine demaination= guanine Pyrimidines (CUT) (one ring) Cytosine deamination= Uracil Uracil methylation= Thimidine |
|
|
Purine Synthesis requirements |
(GAG) -glutamine -Aspartate -Glycine
|
|
|
Orotic Acid accumulation |
1)Orotic Aciduria(BUN: normal, Amonia: normal) no defect in urea cycle, No pyrimidines= megaloblastic anemia Uridine administration
2)OTC malfunction from urea cycle (BUN:decre, Hyperamonemia) Carbamoy phosphate accumulation, being metabolized by UMP synthase
|
|
|
Nucleoside Nucleotide |
Base+sugar Base+sugar+phosphate |
|
|
Lesch- Nyhan Syndrome |
X-Linked recessive HGPRT ( hypoxanthine and guanine to IMP/GMP) No purine salvage Excess uric Acid Retardation,Self mutilation,aggression, hyperuricemia,gout,choreoathetosis |
|
|
Adenine Deaminase deficiency |
-Adenosine to Inosine -Accumulation of ATP/dATP feedback inhibition of Ribonucleotide reductase= No DNA synthesis
|
|
|
SCID in KIDS |
Autosomal recessive Adenine Demainase Deficiency No DNA= No lymphocytes Therapy: gene |
|
|
Xantine Oxidase |
Uric acid conversion from Guanine and Hypoxanthine. Allpurinol inhibits it |
|
|
Genetic code Properties |
1)Unambiguos: 1codon=amino 2)Degenerate: 1 amino by multiple codons (Ex:methionine AUG and Tryptophan UGG) 3)Commaless/nonoverlapping: read from fixed starting point as continuos sequence of bases 4)Universal: Conserved throughout evolution (EX: mitochondria) |
|
|
DNA mutations |
Transitions: Tranversions: -Silent (same amino) -Missence (changed amino similar) -Nonsence (stop) -Frameshift (missreading downstream) -In frame( multiple of 3 bases added downstream normal) -Large segment deletions -Triplet repeat expansion -Splincing mutations |
|
|
Chargaffs Rules |
% A=T % (or U%) % G=C % % Purines=Pyrimidines |
|
|
Fluoroquinolones Target |
Topoisomerase II introduce negative supercoilings to relieve tension. Prevent bacterial DNA replication |
|
|
Chromatin Types |
Euchormatin: Active 10 nm and 30 nm fibers
Heterochromatin:Inactive Highly packaged Chromosomes
|
|
|
DNA replication |
DNA Polymerase: Template Read from 3-->5 (primer req) Synthesis: 5--> 3 Wrong nucleotide: 3--> 5 exonuclease High fidelity
|
|
|
RNA replication |
RNA polymerase: DNA template read: 3--> 5 (no primer) No profreading activity Low fidelity (T) for (U) |
|
|
Helicase |
Open the DNa strand breaking H bonds(unwind) |
|
|
DNA binding proteins |
Prevent from strands reassociating |
|
|
Primase |
RNA primer (5-->3) |
|
|
DNA polymarase functions ? |
Leading Strand: continuos DNA synthesis 5-->3, beginning at the 3 end of the primer Lagging Strand: discontinuos Okazaki fragments Profreading 3-->5 exonuclease |
|
|
RNAase function ? |
Remove primers |
|
|
DNA ligase |
Seal gaps with phosphodiesters bonds (EX. Okasaki fragments) |
|
|
DNA gyrase |
topoisomerase II negative supercoils |
|
|
Inhibitors of Eukaryotic Topoisomerase II |
Tenoposide Etposide antitumorals |
|
|
Eukaryotic DNA polymerase |
ALFA and DELTA: Synthesize DNA GAMMA: replicates mitcochondrial DNA Beta:Repair |
|
|
Telomerase |
Maintain Telomers by adding RNA by reverse transcriptase activity Only in embryonic cells. Might be high in tumoral cells. |
|
|
Reverse transcriptase |
RNA dependent DNA polymerase. Uses an RNA template to produce DNA RETROVIRUSES: HIV (Target of antiretroviral Therapy like AZT,DDc,DDI) HUMANS: TELOMERASE |
|
|
Xeroderma Pigmentosum |
Autosomal Reccesive Thymine dimers Sensitvity to light, skin freckling, ulcerations, cancer. Carcinomas and melanomas early UV radiation repair G1 : excision endonuclease (DNA polymerase, ligase) |
|
|
P53 gene |
Prevents entering a damaged cell to DNA replication Associated with Li Fraumeni SD |
|
|
RB gene |
Tumor suppresor Retinoblastoma |
|
|
Mismatched bases repair |
During: G2 Genes: MSH2, MLH1 Affected: Nonpolyposys colorectal cancer (HNPCC) or Lychc Syndrome. Microsatellite instability |
|
|
Cytosine Demaination Repair |
During G1 Uracil Glycosilase
|
|
|
Microsatellite Instaibility |
Di tri nucleotides repeats dispersed through DNA. If mismach repair is altered numbers of repeats will vary. HNPPC
|
|
|
Types of RNA |
rRNA: most abbundant, ribososmes tRNA:second, carry aa to the ribosome mRNA: aa sequence from DNA thats going to be translated in ribosomes. hnRNA: Pre mRNA snRNA: splicing (nucleous) |
|
|
Eukaryotic RNA polymerases |
RNA Pol I: nucleous--> rRNA (except 5S) RNA Pol II: hnRNA/mRNA RNA Pol III: tRNA and the 5s rRNA |
|
|
Where does RNA Polymerase binds to start Transcription ? |
To the promoter |
|
|
Where Does prokaryotic ribosomes bind to initiate mRNA translation ? |
Shine Delgarno of the 5 unstraslated region |
|
|
Where Does Eukaryotic ribosomes bind to the mRNA ? |
To the 7 methilguanosine cap |
|
|
Eukaryotic Mature mRNA which characteristics have ? |
Process: in the nucleous 1) 7 methylguanosine cap to the 5 end 2)Poly A tail addition 3)No introns
|
|
|
Alternative Splicing is ? |
The pre mRNA is spliced in different forms to produce different proteins from one gene. |
|
|
Ribosomes |
Eukaryotics: 60S and 40S(80S) Big subunit: 5s-5.8s-28s small subunit: 18s
Prokaryotics: 50S and 30S (70S) Big: 5s-23s small: 16s |
|
|
Shiga Toxin(shigella dysenteriae) Verotoxin (Enterohemorragic E. coli) Target ?? |
Inactive 28S halting protein synthesis |
|
|
tRNA Functions? |
1)Pairs with codon in mRNA 2)Picks up aminoacid in the 3rd end |
|
|
RNA polymarase types in Prokaryotes ?? |
JUST ONE Alfa2beta beta |
|
|
STOP AND START CODONS |
START: AUG (methionine),bacterias=fmet
STOP: (UAA-UGA-UAG) |
|
|
B-thalassemia |
Beta chain of HB deficiency Mediterranean areas -Pale,splenomegaly,bone deformities (excessive activity of bone marrow) , fractures |
|
|
Large segement deletions mutations |
Alfa thalassemia: Deletion of one or more of the alfa globin from chromosome 16 Cri-Du-CHAT: deletion of the short arm of chormosome 5 |
|
|
Splice site mutations |
B-thalassemia tay Sachs Gaucher |
|
|
Trinucleotide Repeat expansions mutations |
Expansion of trinucleotides repeats, increase with generatios showing anticipation. 1)Huntingon 2)Fragile X Syndrome 3)Myotonic Dystrophy |
|
|
Huntingon Disease |
Autosomal Dominant (late onset) Trinucleotide repeat expansion -mood disturbance -impaired memory -Hyperreflexia -Gait problems -Chorea -Dystonia -Dementia -Dysphagia |
|
|
Where does translation, transcription takes part ?? |
Translation: Cytoplasm Trasncription: Nucleous |
|
|
Translation Stages: |
1)Initiation: small subunit binding to shine delgarno or 7 methylguanosine. tRNA binds to firs codon AUG with Met. Binds to P site 2)Elongation: Use elongations factors (ef2) and GTP -tRNA binds to A site, peptidyl transferase forms peptide bond-->ribosome moves three codons in mRNA and the A site becomes free.
3)Termination:A site reach stop codon
|
|
|
Pseudomonas Diphteria Toxins |
Inactivate Ef2 used in Elongation ADP rybosylation |
|
|
AMINOGLYCOSIDES |
Bind to 30S --> inhibit translation initiation |
|
|
Tetracyclines |
Elongation inhibitor binds to A site Minocycline Doxicycline |
|
|
Macrolides |
Block elongation Inhibiting 50S in P site Erythromicin |
|
|
Chloranphenicol |
Block Peptidyl transferase
|
|
|
Gray Baby Syndrome |
Babys who receive chloranphenicol Do not have enough glucoronyl trasnferase to allow excretion. Cause: Aplasic anemia,blue lips, cyanosis, death ,low blood pressure |
|
|
Proteins translated on RER ribososmes: |
Secreted proteins Proteins for membrane Lysosomal enzymes |
|
|
Prteins translated in free ribosomes: |
Cytoplasmic proteins Mitochondrial proteins |
|
|
How enzymes are targeted to Lysosomes?? |
Phosphorylation of mannose |
|
|
How translation is designded to happen at RER ?? |
N terminal signal Proteins for : 1)secretion 2)membrane 3)lysosomes |
|
|
Alfa 1 antitrypsin deficiency |
By Liver on to the blood Protect cells as an inhibitor of some proteases released during normal inflamatory response. Genetical disease: accumulationdue ti misfolding leading to cirrhosis. |
|
|
I-Cell disease |
No mannose Phosphorylation, producing lysosomal enzymes to be secreted in the blood. Inclusion bodies in lysosomes Produce: -Coarse features, gingival hyperplasia, macroglossia. -Craniofacial abnormalities -Clubfoot -Growth retardation -Scoliosis |
|
|
Co and Pottranslational mofications to proteins |
1) Glycoslylation 2)Proteolysis 3)Phosphorylation 4)Gamma Carboxylation 5)Phenylation |
|
|
Collagen Types |
I: bone, skin, tendons(Osteo imperfec,Ehler) II: Cartilage, Vitreous humor III: Blood vessels, granulation tissue (keloid) IV: basement membranes(Goodpasture, Alport) |
|
|
Scurvy |
Vit c Deficiency (No Hydroxylation) -Anemia -Petechiae, Echymoses. loose teeth, Bleeding gums -Poor wound healing -Poor bone development |
|
|
Osteogenesis Imperfecta |
Gene mutation -Skeletal deformities -Fractures -Blue sclera
|
|
|
Ehlers Danlos Syndromes
|
Collagen gene and Hydroxylase gene mutation.
-Hyperextensible skin and fragile -Hypermobile joints -dislocations -Varicose veins and ecchymoses |
|
|
Menkes Disease |
X-Linked No cross linking secondary to copper def (lysil Oxidase) Problem at intestine pump -Depigmented steely hair -Arterial tortuosity -Cerebral degeneration -Osteoporosis -anemia |
|
|
Wilsons Disease |
Diferencial with MEnkes Copper cannot be pumped from liver -Kayser-Fleischer rings ( brown ring iris) -Physcological problems -Low ceruloplasmin |
|
|
Activator proteins that bind to response elementsare called ? |
trasncription Factors |
|
|
Especific Transcription Factors bind to ?? |
Enhancer regions to modulate formation of transcription complex |
|
|
Trans. Factor: Steroid receptors |
Biding Site or response element : HRE Function: steroid response Class: zinc finger |
|
|
cAMP response element binding protein (CREB) binds to ? |
Binding: CRE
Function : Response to cAMP class: Leucine |
|
|
Trans. Factor:
Peroxisomes proliferator activated receptors(PPARS) |
Bind to: PPREs
Function: Regulate lipid metabolism Class: zinc fingers |
|
|
Transcription Factor have two Domains ?? |
1) DNA binding domain 2)activation Domain (bind to other TF, interact with RNa pol, Acetylases for chormatin) |
|
|
How does Fibrates Act ?
|
Peroxisomes proliferation lipoprotein lipase expression.
|
|
|
Zwelleger Syndrome |
Peroxisomes def. accumulation of long chain FA. -enlarged liver -Vision problems - high Fe and Cu levels - Abnormal muscle tone - mental retardation |
|
|
Klein Wardemburg syndrome |
PAx gene defect -Dysthopia Canthorum -Pigementary abnormalities (white hair in fornt patch) - Congenital deafness - Limb abnormalities |
|
|
Sonic hedgehog Gene mutation?? |
Holoprosencenphaly |
|
|
Prader Willi Syndrome |
Genetic imprinting in Chromosome 15 where paternal gene is imprinted. - Childhood hyperphagia - Obesity - Hypodonatrophic hypogonadism - Mental Retardation - Hypotonia |
|
|
Recombinant DNA applications: |
-Analyze and altere genes -Recombinant proteins -Prenatal diagnosis -Produce genomic libraries |
|
|
cDNa Libraries Used for: |
1) Sequence genes- identify disease 2) Recombinat proteins 3) Gene replacement therapy 4)transgenic Animals |
|
|
Transgenic MICE |
Introduce a cloned gene into fertilized Ova to produce affected germline.Offspring are transgenic Used to study diseases from early embrionic development through adulthood.
|
|
|
KnockOut Mice |
deletion of a gene |
|
|
Chimeric mice |
Mice compossed of two different cell lines fro two different starin of mice |
|
|
Vectors for recombinant DNA should include : |
1) Restriction site 2)replication Origin 3) resistance to antibiotic
For expression: 1)Promoter 2)Shine delgarno |
|
|
Southern Blot
|
DNA
Determine which fragments of Dna are associated to a probe. |
|
|
Wester Blot |
Analyze proteins Measure amount of antivbodies or antigens |
|
|
Northern Blot |
RNA Measure amounts of mRNA or to measure gene expression. |
|
|
What does Southern Blot with RFLPs search for ? |
Mutations in restriccion endonucleases sites |
|
|
Fragile X Syndrome |
Leading Cause of mental retardation. FMR1 gene in long arm of chromosome X -Large ears -Elongated Face -hypermobile Joints
|
|
|
Uses of PCR: |
1) Compare DNA in Forensic Cases (Paternity) 2)Direct mutation test 3)Diagnosis of viral or bacterial 4)HIV test (when Ab where uniformative, infants whose mothers are HIV pos) |
|
|
Microsatellites Or STRs useful for:
|
Are repeats of Di Tri to tetranucleotides sequence.
useful for genetic Testing. Show some variability in lenght as mutations have expanded or contracted the numbre of repeats |
|
|
Advantages of PCR for HIV ?? And When is used ??
|
1) Positive muche earlier 2) Do not rely on Ab response by the invidual ------ 1) newborn whose mother is HIV pos 2) Early testing after exposing to HIV pos blood |
|
|
Reverse transcriptase PCR (RT-PCR) is used for ?
|
Detects and quantify a especific RNA in a sample.
Used for measure the concentrations of active circulating Virus or VIRAL LOAD |
|
|
Hydrophobic aminoacids |
1) Glycine 2) Alanine 3) Valine 4) Leucine 5) Isoleucine 6) Proline 7)Tyrosine 8)Phenilalanine 9) Triptophan |
|
|
Hydrophilic aminoacids |
1)Arginine 2)Lysine 3)Histidine 4)Aspartate 5)Glutamate 6)Serine 7)threonine 8)Cysteine 9)methionine 10)Asparagine 11)Glutamine |
|
|
Positive Aminoacids ?? |
-Lysine -Arginine -Histidine |
|
|
Negative Aminoacids ?? |
-Aspartate -Gluatamate |
|
|
Aminoacids with sulfur ?? |
-Methionine -Cysteine |
|
|
N-Acetylcysteine Uses: |
1) Acetaminophen intoxication 2) Cystic Fibrosis 3) Hemorragic cistitis (cyclophosphamide) |
|
|
Mapple Syrup disease involved aminoacids ?? |
-valine -Leucine -Isoleucine |
|
|
Ketogenic aminoacids ?? |
-Leucine -Lysine |
|
|
Essential aminoacids ?? |
1)Arginine(only during growth) 2)histidine 3)isoleucine 4)leucine 5)lysine 6)methionine 7)phenylalanine 8)threonine 9)Tryptophan 10)valine |
|
|
Aminoacids involved un cathecolamines synthesis ?? |
1) Phenylalanine 2)Tyrosine |
|
|
Sickle cell anemia is produced by ?
|
Substitution of valine by a glutamate
Rod shaped crystals, anemia 1) Vaso occlusive episodes (1 week) 2) Hemolytic episodes 3) Pain in bones 4)abdomen |
|
|
Test to detect Hemoglobinopathys ?? |
Electrophoresis Normal HBA= no charge no migrattion HBc= two positives charges HBs= One negative charge |
|
|
Protein Turnover ?? |
amount of Broken proteins have to replaced |
|
|
Nitrogen Balance Is? |
Condition in which the amount of nitrogen incorporated each day equal the amount excreted.
|
|
|
Causes of Negative balance ?? |
1) Protein malnutrition 2) A dietary deficiency 3) Starvation 4) Diabetes 5) Infections |
|
|
Causes of positive balance ?? |
1) Growth 2) Pregnancy 3) post surgery 4) Recory from nevative balance conditions |
|
|
How do enzymes modify the rate and the activation energy ?
|
1) the rate in increased by enzymes
2) Decrease the energy of activation |
|
|
Energy needed = 0 |
Reaction at equilibrium |
|
|
Energy needed = >0 |
Thermodinamically nonspontaneous (energy required)
|
|
|
Energy needed = <0 |
thermodinamically spontaneous ( irreversible) |
|
|
Forms to represent enzyme reactions |
1) Michael mentis equation 2) Lineweaver- Burk plot |
|
|
What is a competitive inhibitor ? |
Substance tha ressemble the substrate and compete for binding to the active site of the enzyme. Increase the Km, No effect on Vmax |
|
|
What is an noncompetitive inhibitor ? |
They do not bind to the active site, they bind to regulatory sites in the enzyme.
Decrease Vmax and no effect on Km |
|
|
Examples of competitive inhibitors ? |
Statin drugs: Competitive inhibit (HMG-coa) Methotrexate: inhibits dihydrofolate reductase |
|
|
Which is the best therapy for metanol intoxication ? |
Fomepizole |
|
|
Type of Hormones by its secretion location ?
|
1) Paracrine: act close to the cell
2) Telecrine: Acts far |
|
|
Hormone clasification ? |
1) Hydrophilic ( insulin, Glucagon, cathecolamines) 2)Hydrophobic (Steroids,Calcitrol,Thyroxines,Retinoic Acid) |
|
|
Protein Kinases Cause ? |
1) Phosphrylation of enzymes 2) phosphorylation at genetic levels to incrase enzymes. |
|
|
Hormones related to cAMP receptors ?
|
-Glucagon (Gs)
-Epinephrine Beta receptor (Gs) -Epinephrine Alfa 2 receptor (Gi) -Ach receptors M2 (Gi) |
|
|
Which Protein Kinase is present in the cAMP ? |
Protein Kinase A |
|
|
PIP2 hormones receptors for ? |
-Vasopressin -epinephrine alfa 1 -ACH m1-m3 |
|
|
Protein kinase activated in PIP2 path ?? |
Protein Kinase C |
|
|
Which enzyme is activated by Gq in PIP2 ? |
Phospholipase c |
|
|
cGMP activates which Protein Kinase ?
|
Protein Kinase G
|
|
|
Atrial natriuretic factor accion mechanism ? |
Binds to ANF receptos, activating guanylate cyclase which by a secon messenger acivates PKg relaxing smooth muscle. |
|
|
Nitric Oxide accion mechanism ? |
Difuses into cell activates soluble gualnylate cyclase which by 2nd messenger activates PKg relaxing smooth muscle. |
|
|
Drugs that become NO ? |
Nitroprusside nytroglycerine Isosorbide dinitrate |
|
|
Whats the name of the G protein related to the cGMP pathway ?? |
Theres no G protein |
|
|
Insulin binding to its receptor activates ?? |
Tyrosine Kinase |
|
|
Steps related in the insulin pathway ? |
1- Receptor dimerization 2-hormone binds 3-Tyrosine kinase activated 4-Tyrosine kinase autophosphorylation 5- Insulin receptor substrate binds to receptor (IRS) 6-SH2 domains bind to IRS |
|
|
SH2 domains of tyrosine kinase produce ? |
1) activation of Pi-3 kinase which increases GLUT 4 on membrane of Adipose and muscle 2)Activation og protein phosphatases 3) stimulation of p21ras gene |
|
|
How does E.coli heat stable toxin acts ? |
Stimulates adenyl cyclase in GI increasing cGMP producing diarrhea. |
|
|
Biotin deficiency produces ? |
MCC: raw eggs -Fasting hypoglycemia -Alopecia -Muscle pain -Symptoms related to energy deficiency |
|
|
Biotin is related to which enzymes ? |
ABC enzymes 1) Pyruvate carboxylase ( Gluconeogenesis ) 2) Acetyl Coa carboxylase ( F. acid synthesis) 3) Propionyl Coa carboxylase (Odd carbon metabolism) |
|
|
Thiamine is related to which enzymes ? |
TLCFN 1) Pyruvate dehydrogenase ( Pyruvate to AcOA) 2) Alfa ketoglutarate Dehydrogenase (TCA) 3)Transkelotase (HMP shunt) 4)Branched chain ketoacid DH (val,leu,iso)(Mapple syrup) |
|
|
Thiamine deficiency manifestations ? |
MCC: alcoholism 1) Wernicke (Ataxia,Nystagmus,Opthalmoplegia) 2)Kosakoff ( psychosis, cofabulation ) 3) Wet beri-beri (Dylatated Cardiomyophaty) 4) Dry Beri beri
|
|
|
Niacin is related to ? |
NAD(H) FAD(H) Dehydrogenases
|
|
|
Pellagra is Produced by ? |
Niacin deficiency or Hartnups disease (tryptophan ) |
|
|
Pellagra manifestations |
4D's Dementia Diarrhea Dermatitis Death |
|
|
Folic Acid is related to which enzymes ? |
1) Thymydylate synthase ( Thimidine synthesis in pyrimidine pathway) |
|
|
Folate deficiency may produce ? |
MCC: Alcoholism and pregnancy 1) homocysteinemia : > DVT 2) Megaloblastic anemia 3)Neural tube defects |
|
|
Cyanocobalamin is related to ? |
1) Homocysteine methyltrasnferase 2) Methyl malonyl CoA mutase
|
|
|
Vit B12 deficiency may produce ? |
MCC: pernicious anemia, also vegans, terminal ileum resection, Aging with poor diet, infection D.latum -Megaloblastica anemia -Progressive peripheral neurophaty |
|
|
Pyridoxine is related to which enzymes ? |
1) ALA syntahse 2) Aminotransferases
|
|
|
Vit B6 deficiency manifestations ? |
MCC: Izoniacid therapy -Sideroblastic anemia -Cheilosis-stomatitis -Convulsions |
|
|
Riboflavin deficiency may produce ? |
1) corneal neovascularization 2) cheilosis-stomatitis 3) magenta tongue |
|
|
Vitamin C is related to which enzymes ? |
1) Prolyl and lysyl hydroxylases (collagen) 2) Dopamine Hydroxylase (cathecolamines) 3) Iron absortion (anemia) |
|
|
How does lipid soluble vitamins act ? |
They difuse through the membrane and bind to intracellular receptors, the binding to Dna enhancers by ZN fingers. |
|
|
lipid soluble vitamins and main fucntions ? |
Vitamin A: Growth regulation and maintenace of epithelia, Vision Vitamin D: blood Calcium homeostasis Vitamin K: Carboxylation of Ca biding proteins like goag factors Vitamin E: Antioxidant mainly form lipids |
|
|
Which is the active form of Vitamin D and where is produced ? |
1,25 dyhydroxicholecalciferol and is produced in the kidney. |
|
|
How does body respond to hypocalcemia ? |
1- PTH is released, which activates in the kidney calcitrol. 2-Calcitrol increases the Ca absortion from the gut and reduces renal excretion 3- Calcitrol in presence of PTH produce bone resorbtion |
|
|
Causes of Vitamin D deficiency and may produce ? |
1) bone demineralization 2) Rickets (children) 3) Osteomalacia (adults) ------- 1) Low sunlight 2)Renal disease 3) vit d low diet |
|
|
Biphosphonates are drugs for the treatment of________ and they act inhibiting _______ ? |
Osteoporosis Osteoclasts |
|
|
Vitamin D toxicity may produce? |
-HYPERCALCEMIA Excess Vitamin D can cause bone resorption contrubuting to osteoporosis
|
|
|
Hypercalcemia mainly affect ? |
Renal tissue (early signs: polyuria, polydipsia, nocturia), If not corrected= Ca deposition in renal tissues. |
|
|
Vitamin A in the cells are present As ? |
Retino and retinoic acid : for the epithelium Retinal: for Vision |
|
|
Which is the active form of retinal ? |
The CIS form |
|
|
When light hits rodopsyn, Activates ? |
A G protein that activates cGMP- Phosphodiesterse which reduce cGMP concentration Closing Na channels hyperpolarizing the membrane.This reduce the concetration of glutamate and the optic nerve becomes active sending information to the brain. |
|
|
Vitamin A deficiency manifestations ? |
1) Hyperkeratosis 2) Night blindness 3) Xeropthalmia 4) Frequent infections like pnemounia 5) Bronchitis 6) Bitot spots |
|
|
Vitamin A toxicity Signs and symptoms ? |
- Excessive sweating - Brittle nails -Diarrhea |
|
|
MCC of vit A deficiency in the US ? |
- Fat malabsortion - Liver cirrhosis |
|
|
Vitamin K deficiency predisposition ? |
1) Fat malabsortion ( Bile duct obstruction) 2) Prolonged antibiotics 3) Breast fed new borns 4) Infants whose mother have been treated with anticonvulsivants during pregnancy like phenytoin. |
|
|
Whats the main function of Vitamin K ? |
Gamma carboxylation : Introduce Ca binding sites (gamma glutamyl carboxylase) into proteins that depend on Calcium.
|
|
|
Which coagulation factors depend on vit K ? |
-II (prothrombin) -VII -IX -X -proteins c and s |
|
|
How to distinguish from a Vitamin K and C deficiency ? |
In vitamin C bleeding time is increased, and there are connective tissue problems associated.
In Vit K : the bleeding time s normal, but the PT time is increased, and there associated conditions that predispone to deficiency like fat malabsortion, antibiotics, breast fed new borns. |
|
|
How does coumarins act as anticoagulants ? |
They antagonize the effect of Vit k, and coagulation factors are secreted to the blood with no effect.
|
|
|
Why Heparin is administered with coumarins ? |
Coumarins require 2 or 3 days to reach maximun effect. |
|
|
Vitamin E or alfa tocopherol main functions ? |
Antioxidant of lipids |
|
|
Vitamin E deficiency Signs and symptoms ? |
Hemolytic anemia Acanthocytosis Peripheral neurophaty Ataxia Retinitis pigmentosum causes : Fat malbsortion and prematures |
|
|
Which substance is the common metabolic intermediate during the the well fed state ? |
Acety CoA |
|
|
Which are the main sources for Acetyl coA ? |
1) Carbohydrates 2) Proteins 3) Fat |
|
|
After a meal how carbohydrates are processed to Acetyl CoA ? |
Glycolisis: Glucose is absorbed in the GI tract and with insulin its transformed to pyruvate and then with help of PDH to ACoa |
|
|
Excess energy from the diet is stored as ? |
1) Fatty acids 2) GLycogen |
|
|
Insulin is an ________ hormone and promotes__________ ? |
- Anabolic -Fuel storage |
|
|
Glucago main functions ? |
Respond to hypoglicemia, by promoting synthesis and release of glucose. |
|
|
Which are three major target tissues of insulin ? |
1) Liver 2) Adipose 3) muscle |
|
|
During the well fed stage insulin in the liver muscle and adipose tissues promotes ? |
Muscle: GLucose entry and Glycogen and protein synthesis Liver: Glycogen and Fatty acids synthesis. Adipose: Glucose entry and triglyceride synthesis. |
|
|
During the post absortive state which are the main functions of glucagon, epinephrine? |
Glucagon: Glycogenolysis and gluconeogenesis (Liver only). Epinephrine : release of Aa from muscle and fatty acids from adipose tissue.
|
|
|
What inhibits the production of ATP and starts the production of storage forms of energy ? |
High concentration of ATP inhibit TCA cycle. |
|
|
What conditions must be present to produce Glycogen ? |
1) Insulin 2) High energy level from burning sugars |
|
|
During well fed state the excess of Acetyl CoA will be stored as ? |
Fatty acids in Adipose tissue |
|
|
During prolonged starvation Lypolisis produce high levels of Acetyl Coa ,What happen whith them ? |
They are trasformed to ketone bodies in the liver and dump into the blood as a secondary source of energy. |
|
|
Red blood cells can use which sources for energy ? |
Only Glucose. |
|
|
What are the two major roles ol the liver in fuel metabolism ? |
1) Maintain glucose blood levels 2) Synthesize Ketones |
|
|
During the well fed state the liver gets his energy mainly from ? |
Oxidation of aminoacids |
|
|
Lipoprotein lipase is located in ______ and its major function is______ ? |
Adiposse tissue Release fatty acids from lipoproteins |
|
|
Lipoprotein Lipase respond to ? |
Insulin |
|
|
Hormone sensitive lipase fucntion ? |
Release fatty acids during fasting to the blood from fat cells. |
|
|
During the Well fed state the energy levels in the liver are high from burning _________ and in the post absortive state are high from burning _____? |
-Sugars -Fat |
|
|
Which cells can carry glycolisis ? |
Every cell in the body |
|
|
How is glucose tranported into the mucosal cells ?
|
By a Na/glucose trasnporter
|
|
|
What kind of GLUT transporter does the Liver and pancreas have ? |
GLUT 2 an server as the B2 glucose sensors. |
|
|
GLUT 4 is present in ? |
Muscle and adipose tissue and increase in response to insulin |
|
|
GLUT 1 and GLUT 3 are in ? |
All other tissues and have a high affinity for glucose |
|
|
Glycolysis products are ? |
From one glucose :
2 pyruvates 2 substrate level phosphorylation 1 NADH |
|
|
Glucokinase function ? |
In the liver and pancreas Traps glucose adding phosphate Insulin estimualtes |
|
|
Which is the rate limiting enzyme in the glycolysis pathway ? |
PFK 1
|
|
|
What activates and inhibits PFK1 ? |
Inhibits : Glucagon, ATP, Citrate Estimulates: Insulin by PFK2 and AMP |
|
|
Deficiency in Pyruvate kinase produce ? |
The 2nd most common cause of hemolytic anemia Hemolituc anemia No heinz bodies Increased 2-3 BPG |
|
|
Pyruvate Kinase function ? |
Trasnform Phosphoenolpyruvate to Pyruvate. Produce ATP as substrate lever Phosphrylation. |
|
|
2 ATP are produces as substrate lever phosphorylation ? |
1 ) 1,3 Biphosphoglycerate 2) Phosphoenolpyruvate |
|
|
Which steps in the Glycolysis pathway are irreversible ? |
1) Glucokinase or Hexokinase 2) PFK 1 3) Pyruvate Kinase |
|
|
Patient which presents:Vomits, Diarrhea, Lethargy, Hepatomegaly and jaundice, and mental retardation, also cataracts
Probable Dx ? |
Galactosemia
- Glacatose 1P urydiltransferase deficiency |
|
|
Patient with cataracts should suspect ? |
Galactokinase deficiency or Aldolase reductase Patients with galactosemia or diabetes |
|
|
Lactase deficiency ? |
Diarrhea Cramps Bloating |
|
|
2-3 BPG function ? |
Decrease O2 affinity for hemoglobin and allows to O2 be kicked out from the erythrocyte to the tissues. |
|
|
Sucrose is broke down into ? |
Glucose and fructose |
|
|
Essential Fructosuria |
Fructokinase defiency Benign condition |
|
|
Infant previuosly normal, who started Weaning process developed lethargy, vomits, Hepatomegaly, Hypoglycemia, Hyperuricemia and renal failure ? |
Hereditary Fructose Intolerance Fanconi sindrome ( proximal renal disorder) |
|
|
Pyruvate Dehydrogenase is located in and its function is ? |
PDH converts Pyruvate to Acetyl- CoA inside the mitochondria, which will serve for either fatty acids synthesis or ATP production in TCA. |
|
|
Which compund inhibits PDH ? |
Its own product, Acetyl Coa |
|
|
What PDH requires for work ? |
T-- Thiamine L-- lipoic acid C-- COA F-- FAD N-- NAD |
|
|
Wernicke- Korsakoff Syndrome |
Thimine (B1) deficiency in alcoholics Ataxia, opthalmoplegia, nystagmus Memory loss and confabulation Cerebral hemorrage Wet Beri Beri : Congestive heart failure |
|
|
Name 3 enzymes which Are TLCFN |
1) PDH 2) Alfa ketoglutarate DH 3) Brnached chain ketoacid DH |
|
|
Which products give rise to Acety Coa for TCA cycle ? |
Glucose Aminoacids Alcohol fatty acids Ketones |
|
|
Which is the rate limiting in the TCA cycle ? |
Isocitrate Dehidrogenase Inhibited : ATP and NADH Estimulated: ADP
|
|
|
How many ATP are produced by each acetyl Coa ? |
12 ATP (x2) |
|
|
Requirements of alfa ketoglutarate dehydrogenase ? |
TLCFN |
|
|
Which enzyme catalizes the third substrate level phosphorylation ? |
succinyl Coa synthase |
|
|
How does the TCA cycle gets regulated ? |
Isocitrate DH is inhibited (ATP or NADH) and citrate accumulation turns off PFK 1 which in turn turns off Glycolisis. Exception on the liver whic has PFK 2 |
|
|
FADH2 is produced from ? |
Succinate By succinate dehydrogenase or complex 2 |
|
|
Electron transport chain components ? |
1) NADH dehydrogenase or Complex I 2) Coenzyme Q 3) Complex III 4)Cytochrome C 5) Complex IV |
|
|
Some electrons are transfered directly to Coenzyme Q ? |
From: 1) succinate Dehydrogenase ( FADH2) 2) Fatty acyl CoA dehydrogenase (FADH2) 3) Glycerol P shuttle (NADH) |
|
|
How a Proton gradient is maintained in the Mitochondria intermembrane space ? |
The energy generated by the flow of electrons is used by translocators to pump protons from the matrix across the inner mebrane |
|
|
Which complex is in charge of producing ATP by pxidative phosphorylation ? |
F0F1 ATP synthase, protons flow into the mitochondria through the F0 and the energy is used by F1 to phosphprylate ADP to ATP.
|
|
|
HOw much ATPs are produced by the electrons of an NADH ? |
3 ATPS
|
|
|
How much ATPs are produced by the electrons of an FADH2 ? |
2 ATPs |
|
|
Oxidative Phosphorylation is inhibited by ? |
- ATP - Low O2 - Increased NADH FADH2 |
|
|
How does Cyanide works ? |
Binds irreversibly to complex IV ( cytocrome c), stoping electron transport and ATP production |
|
|
Cyanide Treatment ? |
1) Nitrites: transform hemoglobin to methemglobin, which cyanide binds faster than that to complex 2) Thiosulfate: transforms Cyanide to thyocynate which is less toxic |
|
|
CO intoxication |
CO binds to FE2 in hemoglobin and also in complex 4 (cytochrome oxidase ) preventting transportation of electrons to O2. |
|
|
Carbon monoxide intoxication symptoms ? |
1) red cherry color of lips and cheeks 2) Respiration depression 3) coma |
|
|
How does uncouplers work ? |
They block the entrance of protons to F0 that way ATP its no procuded and energy is lost as heat , low concentrations of ATP increases back the cycle. - 2,4 dinitrophenol -Aspirin -thermogenin |
|
|
Reactive Oxygen Species ? |
1) superoxide 2) Hydrogen peroxide 3) Hydroxyl radical |
|
|
Whats the mechanism behind reperfusion injury ? |
When tissue has been depreved from Oxygen, ATP will bel low and NADH would be high, if we introduce 02 back theres is a burst of activity in the ETC releasing ROS. |
|
|
Defense mechanism against ROS ? |
1) superoxide dismutase 2) Catalase 3) glutathione peroxidase 4) Vitamin E |
|
|
Mitochondrial inherited diseases ? |
MELAS LEBER Myoclonic epilepsy with ragged red fibers |
|
|
Whats known as respiratory control ? |
If O2 is limited the rate oxidative phosphorylation decreases and concentration of NADH and FADH2 increases, the high concentrations of NADH in turn inhibits the TCA cycle.
If O2 is normal and ADP is low , ADP allosterically activates isocitrate dehydrogenase increasing NADH and FADH2 those in turn increase ETC increasing ATP synthesis. |
