First Aid Usmle Step 1: Biochemistry Flashcards
What is a nucleoside?What is a nucleotide?Which are the purines?Which are the pyrimidines?
Side = base + (deoxy)ribose [sugar]Tide = base + (deoxy)ribose [sugar] + phosphaTeWhich are the purines? "pure as gold" = Adenosine, GuanosineWhich are the pyrimidines?"CUT the pyramid" = Cytosine, Uracil, Thymine
In the nucleotide synthesis pathway, describe how purine synthesis differs from pyrimidine synthesis. Fr the following drugs, describe how they interfere with purine or pyrimidine synthesis.LeflunomideMethotrexatem Trimethoprim and Pyrimethamine5-Fluorouracil6-MercaptopurineMycophenolate and RibavirinHydroxyurea
Disrupt pyrimidine synthesisLeflunomide: inhibits dihydroorate dehydrogenase*Methotrexatem Trimethoprim and Pyrimethamine: inhibit dihydrofolate reductase, resulting in decreased dTMP in humans, bacteria and protozoa respectively.5-Fluorouracil*: inhibits thymidylate syhtnaseDisrupt purine synthesis6-Mercaptopurine (6-MP): and its prodrug azathioprine inhibit de novo purine synthesisMycophenolate and Ribavirin: inhibit inosine monophosphate dehydrogenaseDisrupt purine and pyrimidine synthesisHydroxyurea: inhibits nucleotide reductase
Adenosine deaminase deficiencymetabolic deficiency:symptoms:
metabolic deficiency:- absence of adenosine deaminase resulting in increased dATP which is toxic to lymphocytes- one of the major causes of autosomal recessive SCIDsymptoms:
Lesch-Nyhan Syndromepattern of inheritance:metabolic deficiency:symptoms:
pattern of inheritance:- x-linked recessive metabolic deficiency:- defective purine salvage due to absence of HGPRT which converts hypoxanthine to IMP and guanine to GMP- this results in excess uric acid production and de novo purine synthesissymptoms:remember HGPRT- Hyperuricemia- Gout- Pissed off (aggression)- Retarded (intellectual disability)- DsyTonia
Describe organization of eukaryotic DNA/gene
Coding strand : 5' ..Enhancer.............CAATbox(-75)....TATAA box(-25)....transcription start site(+1)......exon....intron...exon.....AAATAAA..3'-on exam always assume it's the 5'-3' coding strand that you see-5'-3' coding strand (same as RNA)-3'-5' template strand (compl. To RNA)-5'-3' mRNA-(CAAT & TATAA are the promoter region)
Regulation of gene expression
-Promoter - CAAT and TATA box region upstream. RNA poly II and other transcription factors bind here.-Enhancer - - Silencer
Lac operon
Low glucose: hi AC activity -> hi cAMP -> activation of CAP induces transcription only if repressor is not boundHigh lactose: unbinds repressor from the opersator and increases transcription
Nucleotide excision repair
excision endonucleases release oligonucleotide containing damaged bases. DNA polymerase fills in gap and ligase seals it. Repairs bulky kelix-distortine lesions. Occurs in G1 phase. Defect in xoderma pigmentosum, which prevents repair of pyrimidine dimers because of UV exposure
Base excision repair
Base specific glycosylases remove altered base and creates AP site. One or more nucelotides are removed by AP endonucleases that clease the 5' end, Lyase cleases the 3' end, and DNA poly 3 fillgs gap and ligase seals it. ........... Important fo cytosine deamination and nitrates from meat?
Mismatch repair
Newly synthesized strand is recognized, mismatched nucleotides are removed, and the gap is filled and resealed. Occurs in G2 phase-MSH2 finds mismatch-MCH1 takes it out-Defective in Lynch syndrome (HNPCC)
What is the splicing process of pre-mRNA?What is the name for antibodies againsr splicesosome snRNPs and what disease are they highly specific for? What disease are anti-UI RNP antibodies associated with?*
What is the splicing process of pre-mRNA?*What is the name for antibodies againsr splicesosome snRNPs and what disease are they highly specific for?- antibodies to spliceosomal snRNPS (aka *anti-SMITH antibodies) are highly specific for SLEWhat disease are anti-UI RNP antibodies associated with?- mixed connective tissue disease
How do cyclins and tumor supressors regulate cell cycle
CDK - Constitutive and inactiveCyclin - activate CDKsCyclin-CDK complexes - phosphorylate other proteins to coordinate cell cycle progression; must be activated and inactivated at appropriate times for cell cycle to progressTumor suppressor - p53 induces p21, which inhibits CDKs -> hypophos (activation) of Rb -> hypophos Rb binds and inactivates E2F -> inhibit G1-S progression. ------Mutation in these genes recsult un unrestrained cell division (Li-frau)
Permanent cells
-Neurons, skeletal and cardiac muscle, RBC-Remain in Go phase
Stabile (quiescent) cells
-Hepatocytes, lymphocytes-Enter G1 from Go when stimulated
Labile cells
-Bone marrow, gut epithelium, skin, hair follicles, germ cells-Never go to Go but rapidly divide
Cells rich in RERCells rich in SER
RER - mucus secreting goblet cells of small intesting and antibody secreting plasma cellsSER - liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads
I cell disease
-Inherited lysosomal storage disorder.-Defect in phosphotransferase -> golgi cant phosphorylate manonose on glycoproteins (low mannose 6 phosphate) -> proteins/hydrolytic enzymes cannot be transported to lysosomes and is transported extracellularly -> generalized inflam-Symptoms - coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosome enzymes
Kartagener syndrome
-aka primary ciliary diskynesia-immotile cilia due to dynein arm defect.-Symptoms - male and female infertility, bronchiectasis, recurrent sinnusitis, situs inversus - know difference between this and CF
Osteogenesis imperfectapattern of inheritance:mutation:symptoms:
pattern of inheritance:- genetic bone disorder (brittle bone disease)mutation:- caused by a variety of gene defects but most commonly in COL1A1 and COL1A2- most common form is autosomal dominant with decreased production of otherwise normal type 1 collagensymptoms:- multiple fractures with minimal trauma (can be concused with child abuse)- blue sclerae due to translucent connective tissue over choroidal veins- hearing loss (abnormal ossicles)- sometimes tooth abnormalities (dentinogenesis imperfecta)
Draw the pathway for the synthesis of collagen and note the location and steps. and diseases
cleavage done in step 5 is done y procollagen peptidase and is also deficiency in ED
Ehlers-Danlospattern of inheritance:mutation:symptoms:
pattern of inheritance and mutation:- faulty collagen synthesis - multiple types with variable inheritance, AD and ARsymptoms: are acutally dependent on the type:- hypermobile type = joint instability/hypermob --> most common- classic type = joint and skin symptoms (hyper extensible skin), caused by a mutation in collagen V - vascular type = (vascular and organ rupture), easy bruising: caused by deficiency type III collagen
Menkes disease
pattern of inheritance:- X-linked recessive connective tissue diseasemutation:- caused by impaired copper asoprtion and transport due to defective Menkes protein (ATP7A)- results in decreased activity of lysyl oxidase (of which copper is a necessary co-factor)symptoms:- brittle, kinky hair- growth retardation- hypotonia
Elastin
-Stretchy protein in skin, lungs, large arteries, es-Rich in unhydroxylated glycine, proline, and lysine-Fibrin scaffolding for stability-Broken down by elastase, which is normally inhibitted by alfa antitrypsin deficiencyDiseases - Marfans, emphysema
RNA interferance
using double stranded RNA (siRNA of miRNA) that is complementary ot target mRNA. Th dsDNA separates and promotes degradation of the target mRNA (knocking down gene expression
Mosaicism definition and examples
Presence of genetically distinct cell lines in the same individual1 - McCune Albright syndrome - due to mutation in Gprotein signaling. Presents with unilateral cafe au lait spots, polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormlities2 - turners syndrome - 45 XO/ 46 XX
Uniparental disomy
Offspring receives 2 copies of a chromosome from 1 parent and no copy from the other parentConsider UPD in an individual with a recessive disorder when only one parent is a carrierHeterodismony -> meiosis 1 error Aa + AA -> AaIsodismony -> meiosis 2 error Aa + AA -> aa
Imprinting
-At a loci, only one allele is active and the other is inactive (imprinted/inactivated by methylation)-This is a normal but if the active allele is defective/mutated, then it will cause pathology-Both Prader wili and angelman are due to mutation/deletion of gene on chromosome 15 in the "active" gene....not directly due to imprinting
Prader willi
-Papa mutation/deletion & maternal imprinting-Symptoms - hyperphagia, obesity, intelectual disability-25 % due to maternal UPD - (2 maternally imprinted gene are received; no paternal gene)
Angelman
-Mama mutation/deletion & paternal imprinting-Symptoms - inappropriate laughter, intellectual disability, seizure, ataxia-5% due to paternal UPD - (2 paternally imprinted genes are received; no maternal gene received)
Hypophosphatemic rickets
Inherited X inked disorder resulting in increased phosphate wasting at the proximal tubule-Rickets - like presentation
X link dominant disorders
Hypophosphatemia, Rett syndrome, Fragile X syndrome, Alport
Autosomal dominant diseases
-Achondroplasia-ADPKD-FAP-Familial hyperchol-Hereditary hemorrhagic telangietasia-Hereditary spherocytosis-Hungtinton disease-Lifraumeni-Marfan-MEN-NF1 , NF2-Tuberous sclerosis-von Hippel Lindau disease
Achondroplasiapattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominant, full penetrancemutation: fibroblast growth factor receptor (FGFR3) inhibiting chondrocyte proliferation (FGFR3 activation normally has a NEGATIVE effect on growing bone. The mutation produces a constitutively active receptor resulting in severely shortened bones)symptoms:- most common cause of dwarfism- limb length affected more than head or torso size
Autosomal dominant polycystic kidney diseasepattern of inheritance:mutation:symptoms:
Autosomal dominant polycystic kidney diseasepattern of inheritance: autosomal dominantmutation: in PKD1 (located on chromosome 16; note polycystic kidney has 16 letters) or PKD2 (C4)symptoms: - bilateral, massive enlargement of kidneys due to multiple large cysts
Familial Adenomatous Polyposispattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominantmutation: mutation on chromosome 5q (APC gene)symptoms:- colon becomes covered with adenomatous polyps after puberty. - progresses to colon cancer unless resected
Familial hypercholesterolemiapattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominant mutation: elevated LDL due to defective or absent LDL receptor. symptoms:- severe atherosclerotic disease early in life- corneal arcus (deposition of lipid in peripheral corneal stroma)- tendon xanthomas --> classically Achilles tendon
Hereditary hemorrhagic telangiectasiapattern of inheritance:mutation:symptoms:
pattern of inheritance:autosomal dominant mutation: blood vessel related (TGF-beta signaling)symptoms:- branching skin lesions (telangiectasis)- recurrent epistaxis- skin discolorations- AVMs- GI bleeding- hematuria(aka Osler-Weber-Rendu syndrome)
Hereditary spherocytosispattern of inheritance:mutation:symptoms:tests:treatment
pattern of inheritance: autosomal dominantmutation: spectrin or ankyrin defect resulting in spheroid erythrocytes. Spheres tend to get trapped in spleen (by macrophages) resulting in extravascular hemolysis. symptoms:- hemolytic anemia, jaundice, splenomegaly- increased MCHC, increased RDW (reticulocyte count)tests:- demonstrates osmotic fragility - coombs test is negativetreatment: splenectomy
Huntington diseasepattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominantmutation: trinucleotide repeat (CAG)on chromosome 4), with expansion over generations (genetic anticipation)symptoms:- psychiatric disease- dementia- choreiform movements- MRI showing atrophy of the caudate head
Li-Fraumeni Syndromepattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominantmutation: TP53, a tumor suppressor genesymptoms:- multiple malignancies at an early age- also known as SBA cancer syndrome (sarcoma, breast, leukemia, adrenal gland)
Marfan Syndromepattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominantmutation: mutation in FBN1 gene on chromosome 15 resulting in defective fibrillin and absence scaffolding for elastin formation --> connective tissue tissuessymptoms:- tall with long extremities- pectus excavatum- hypermobile joints- long, tapering fingers and toes- cystic medial necrosis of aorta --> aortic incompetence and dissecting aortic aneurysms- floppy mitral valve- subluxation of lenses, usually upward and temporally.
Multiple endocrine neoplasias (MEN) 1(aka Wermer syndrome)pattern of inheritance:mutation:symptoms:
REMEMBER 3 P'spattern of inheritance: autosomal dominant with incomplete penetrancemutation: in MEN1 genesymptoms:- parathyroid hyperplasia (90%)- pancreatic islet cell tumors (ZES 50%, insulinoma 20%)- pituitary tumors (in 2/3 of patients with MEN 1)
What is Zollinger-Ellison syndrome?
Peptic ulcers resulting from excess secretion of gastrin from a pancreatic islet cell tumor.
Multiple endocrine neoplasias (MEN) 2A, aka Sipple Syndromepattern of inheritance:mutation:symptoms:
REMEMBER "2 Ps 1M"pattern of inheritance: autosomal dominant with incomplete penetrancemutation: RET gene (proto-oncogene that encodes a tyrosine kinase. Absence of RET associated with Hirschsprung disease while gain of function mutation is associated with MEN 2A and 2B)symptoms:- medullary thyroid cancer (100% people with MEN 11A)- pheochromocytoma (1/3)- hyperparathyroidism (>50%)
Multiple endocrine neoplasias (MEN) 2Bpattern of inheritance:mutation:symptoms:
REMEMBER "MMMP"pattern of inheritance: autosomal dominant with incomplete penetrancemutation: RET gene (proto-oncogene that encodes a tyrosine kinase. Absence of RET associated with Hirschsprung disease while gain of function mutation is associated with MEN 2A and 2B)symptoms:- mucosal neuromas (100%) - in nasopharynx, oropharynx, larynx and conjunctiva- medullary thyroid carcinoma (more aggressive than in MEN 2A)- marafanoid body habitus (long/lanky)- pheochromocytoma
Neurofibromatosis type 1 (Von Recklinhausen disease)pattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominant, 100% penetrance with variable expressionmutation:- mutations in the NF1 gene on chromosome 17symptoms:- cafe-au-lait spots- cutaneous neurofibromas- optic gliomas- pheochromocytomas- Lisch nodules (pigmented iris hamartomas)
Neurofibromatosis type 2pattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominant mutation:- NF 2 gene on chromosome 22l; "type 2 = 22"symptoms:- bilateral acoustic schwannomas- juvenile cataracts- meningiomas- ependymomas (ependymoma is a tumor arising from the ependymal cells lining the ventricles of the brain and the center of the spinal cord. Usually arise in the floor of the 4th ventricle resulting in sx of headache, nausea and vomiting by obstructing the flow of cerebrospinal fluid. This obstruction may also cause hydrocephalus.)
Tuberous sclerosispattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominant with variable expressionmutation:? neurocutaneous disorder with multi-organ system involvementsymptoms:- numerous benign hamartomas (benign, focal malformation that resembles a neoplasm in the tissue of its origin)- cognitive impairment, epilepsy and skin lesions (facial angio fibromas and adenoma sebaceum)
von Hippel-Lindau diseasepattern of inheritance:mutation:symptoms:
pattern of inheritance: autosomal dominantmutation:- associated with deletion of VHL (tumor suppressor) gene on chromosome 3 (3p) [VHL = 3 = chromosome 3]symptoms:- numerous tumors, both benign and malignant- capillary hemangiomas (hemagioblastomas) of the brain or brainstem- associated with renal cell carcinoma- associated with pheochromocytomas
Autosomal recessive disease
- albinism- ARPKD- cystic fibrosis- glycogen storage disease- hemochromatosis- Kartagener syndrome- mucopolysaccharidoses- phenylketonuria- sickel cell anemia
Cystic Fibrosis:genetics:pathophysiology:diagnosis:complications:treatment:
genetics:- autosomal recessive defect in CFTR gene on C7- commonly a deletion of Phe508- most common lethal genetic disease in caucasian peoplepathophysiology:- CFTR encode a ATP-gated Cl- channel that secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glands- most common mutation (3 bp deletion that removes phenylalanine at 508) --> impaired post-translational processing (folding/glycosylation) --> retained in RER and targeted for proteasomal degradation --> less chloride channels to cell membrane surfaceRemember that:- in sweat --> CTFR channel responsible for reabsorbing chloride. Absence = high Cl content in sweat- in gut/lungs --> CTFR channel responsible for excreting chloride. Absence = thick mucus due to absence of Na+ and thus, less water in mucusdiagnosis:- increased Cl- concentration (> 60 mEq/L) in sweat is diagnostic- can present with contraction alkalosis and hypokalemia- increased immunoreactive trypsinogen (newborn screening)complications:- recurrent pulmonary infections, chronic bronchitis and bronchiectasis --> reticulonodular pattern on CXR- pancreatic insufficiency, malabsorption with steatorrhea, fat-soluble vitamen deficiency, biliary cirrhosis, liver disease.- meconium ileus in newborns- nasal polyps, nail clubbingtreatment:- multifactorial - azithromycin as anti-inflammatory agent- pancreatic enzymes for insufficiency
What is the comprehensive list of X-linked recessive disorders?
"Oblivious Female Will Often Give Her Boys Her X-Linked Disorders"Ornithine transcarbamylase deficiencyFabrey diseaseWiskott-Aldrich syndromeOcular albinismG6PD deficiencyHunter syndromeBruton agammaglobulinemiaHemophila A and BLesch-Nyhan syndromeDuchenne (and Beckers)
Duchenne Muscular Dystrophypattern of inheritance:mutation:pathophysiology:tests:symptoms:
pattern of inheritance: x-linked recessivemutation: usually a frameshift or non-sense mutation resulting in truncated dystrophin protein leading to inhibition of muscle regenerationpathophysiology:- dystrophin gene = largest protein coding human gene leading to increased chance of spontaneous mutation- dystrophin helps anchor muscle fibers, primarily in skeletal and cardiac muscle- connects intracellular cytoskeleton (actin) to the transmembrane proteins alpha and beta-dystroglycan, which are connected to the ECMtests:- increased creatinine kinase and alodlase are seen symptoms:- weakness beginning in pelvic girdle muscles and progressing superiorly- pseuedohypertrophy of calf muscles due to fibrofatty replacement of muscle- Gower manuever - patients use upper extremities to help them stand/rise- onset before 5 years old- cardiomyopthy - common cause of death
Becker Muscular Dystrophypattern of inheritance:mutation:symptoms:
pattern of inheritance: x-linked recessivemutation: non-frameshift insertions in dystrophin gene resulting in partially functional dystrophinsymptoms:- less severe than duchennes- onset in adolescence or early adulthood
Mytonic type 1 muscular dystrophypattern of inheritance:mutation:symptoms:mnemonic:
pattern of inheritance: autosomal dominantmutation:- CTG trinucleotide repeat expansion in DMPK gene- results in abnormal expression of myotonin protein kinase leading to the below symptomssymptoms:- myotonia- muscle wasting- cataracts- testicular atrophy- frontal balding- arrhythmiamnemonic:My Tonia, My Testicles (testicular atrophy), My Toupee (frontal balding), My Ticker (arrhythmia)
Fragile X Syndromepattern of inheritance:mutation:symptoms:mnemonic:
One of the muscular dystrophiespattern of inheritance: X-linked dominant inheritancemutation:- trinucleotide repeat disorder (CGG) in the FMR1 gene leading to methylation and decreased expressionsymptoms:- 2nd most common cause of intellectual disability- post-pubertal macro-orchidism (enlarged testes)- long face with large jaw- large, everted ears- autism- mitral valve prolapsemnemonic:- fragile *X* = Xtra large teXragile *X* = *X*tra large testes, jaws and ears
What are the 4 different trinucleotide expansion diseases? And what is the nature of the trinucleotide expansion?
What are the 4 different trinucleotide expansion diseases? And what is the nature of the trinucleotide expansion?*X-Girlfriend's First Aid Helped Ace My Test"Fragile X = CGGFriedreich ataxia = GAAHuntington disease = CAGMyotonic dystrophy = CTG
Down Syndrometrisomy:Etiologyincidence:findings:- on first trimester US- on second trimester quad screen- after birthco-morbidities
trisomy: Ch21 (remember, Drinking Age)Etiology: -95% due to meoitic nondisjunction-4% due to unbalanced Robertsonian translocation b/t chrom 14 & 21-1% due to mosaicismincidence: 1:700findings:on first trimester US- increased nuchal translucency- hypoplastic nasal bone- decreased serum PAPP-A- increased free beta-HCGon second trimester quad screen- decreased alpha-feto protein- increased beta-hCG- decreased estriol- increased inhibin Aafter birth- flat facies- intellectual disability- epicanthal folds- single palmar crease- gap between 1st 2 toes- duodenal atresia- ASDsco-morbidities- increased risk of alzheimer's (as amyloid precursor protein is on C21)- increased risk of ALL and AML-duodenal atresia, ASD, VSD, Hirshprung
Edwards Syndrometrisomy:incidence:findings:- on first trimester US- after birthprognosis
trisomy: C18, Election age is 18!incidence: 1:8000findings:on first trimester US- PAPP-A and free beta-HCG are decreased- quad screen shows decreased AFP, Beta-HCG, estriol, inhibin Aafter birth- severe intellectual disability- rocker bottom feet- micrognathia (small jaw)- low-set EARS- clenched hands with overlapping fingers- prominent occiput- congenitial heart diseaseprognosis- death usually within 1 year of birth
Patau Syndrometrisomy:incidence:findings:- on first trimester US- after birth
trisomy: C13, think of age of Puberty (13)incidence: 1:15,000findings:on first trimester US- severe intellectual disability- rocker bottom feet- microphthalmia- microcephaly- cleft liP/Palata- holoProsencephaly- Polydactyly- congenital heart disease- cutis aplasia- death usually in one year of birth
Lab values for autosomal trisomies
everything decreased for all 3 disorders except increased HCG in down syndrome
Turners
The only non lethal monosomy
Klinefelter
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Define what a Robertsonian Translocation is
- chromosomal translocation commonly involving Ch pairs 13, 14, 15, 21 and 22- one of the most common types of translocation- occurs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost- balanced translocations usually do not cause an abnormal phenotype while unbalanced can
Cri-du-chat syndromemutation:findings:
mutation:- congenital microdeletion of short arm of chromosome 5 (46,XX or XY,5p-)symptoms:- microcephaly- modester to severe intellectual disability- high pitched mewing/crying- epicanthal folds- cardiac abnormalities (VSD)
Williams Syndromemutation:findings:
mutation:- congenital microdeletion of long arm of chromosome 7 (deleted region includes elastin gene)findings:- distinctive "elfin" facies- intellectual disability- hypercalcemia- developed verbal skills- extreme friendliness with strangers- cardiovascular problems
DiGeorge Syndromemutation:findings:
mutation:- microdeletion at 22q11 with variable presentation resulting in aberrant development of 3rd and 4th pharyngeal pouchesfindings:CATCH 22- cleft palate- abnormal facies- thymic aplasia (T cell deficiency)- cardiac defects- hypocalcemia 2ndary to parathyroid aplasia
NUTRITION
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What are the fat soluble vitamins? Where are they absorbed?What sorts of conditions result in their deficiency?
What are the fat soluble vitamins? Where are they absorbed?*- A, D, E, K- absorption depends on the gut and pancreas*What sorts of conditions result in their deficiency?*- malabsorption syndromes with steathorrhea (fatty stools) such as cystic fibrosis and sprue- mineral oil intake can also cause fat-soluble vitamin deficiency*
The following are ALL water soluble vitamins. For each vitamin, provide the alternative name and the name of the cofactor it is a precursor to if relevant:B1B2B3B5B6B7B9- where is it stored and for how long?B12- where is it stored and for how long?CB-complex deficiencies often result in what triad of symptoms?
B1: thiamine, TPPB2: riboflavin, FAD, FMNB3: niacin: NAD+B5: pantothenic acid, CoAB6: pyridoxine, PLPB7: biotinB9: folate- stored in liver for 3-4 monthsB12: cobalamine- stored in liver for 3-4 years C: ascorbic acidB-complex deficiencies often result in what triad of symptoms?- dermatitis, glossitis and diarrhea
Vitamin Aalternative name:FunctionWhat happens if there's a:deficiency:excess:
Vitamin Aalternative name: retinolFunction-antioxidant, visual pigments, epithelial cell differentiation, treats measels and AML type M3What happens if there's a:deficiency:- night blindness (nyctalopia)- dry, scaly skin (xerosis cutis)- corneal degeneration (keratomalacia)- bitot spots on conjunctiva- immunosuppression excess:- acute toxicity: N/V, vertigo, blurred vision- chronic toxicity: alopecia, dry skin, hepatic toxicity, arthalgias, pseudotumor cerebri- teratogenic: (cleft palate, cardiac abnormalities) thus a negative pregnancy test and two forms of contraception are required before isotretinoin (vit A derivative) is prescribed
Vitamin B1 alternative name:function:What happens if there's a:deficiency: (give pathophys, 3 syndromes)diagnosis:
alternative name: thiaminefunction:- required for thiamine pyrophosphate (TPP), which is a co-factor for several dehydrogenase enzyme reactions. think ATP:- alpha-ketotglutarate dehydrogenase (TCA)- transketolase (HMP shunt)- pyruvate dehydrogenase (connects glycolysis to TCA)- branched chain ketoacid dehydrogenaseWhat happens if there's a:deficiency:- results in impaired glucose breakdown, leading to ATP depletion which is worsened by glucose infusion [why we given thiamine BEFORE glucose]-highly aerobic tissues (brain, heart) are affected first1. Wernicke-Korsakoff syndrome:- confusion, ophthalmoplegia, ataxia +- confabulation, personality change, permanent memory loss- damage to medial dorsal nucleus of thalamus and mammillary bodies 2. Dry BeriBeri:- polyneuritis, symmetrical muscle wasting3. Wet BeriBeri- high-output cardiac failure (dilated cardiomyopathy)- edema4. Lactic acidosis due to lack of PDHdiagnosis:- measured levels- increase in RBC transketolase activity following thiamine administrationMCC: Alcoholism - alcohol inhibits thiamine uptake
Vitamin B2alternative name:function:What happens if there's a:deficiency:
Vitamin B2alternative name: riboflavinfunction: component of the two flavins FAD and FMN, used in redox reactions i.e. for succinate dehydrogenase rxn in TCA cycle.What happens if there's a:deficiency:- cheilosis (inflammation of lips, scaling and fissures at corners of mouth)- corneal vascularization
What is Hartnup disease? What vitamin deficiency does it result in?
What is Hartnup disease?*- autosomal recessive- deficiency of neutral amino acid transporters in the proximal renal tubular cells and on enterocytes --> neutral aminoaciduria--> decreased absorption from gut--> decreased tryptophan for conversion to niacin--> pellagra-like symptomsRX: high-protein diet and nictoinic acid* What vitamin deficiency does it result in?- vitamin B3 deficiency --> niacin
Vitamin B3alternative name:function:What causes its deficiency:What happens if there's a:deficiency: excess
alternative name: niacin function: - constituent of NAD+, NADP+- derived from tryptophan- synthesis requires B2 and B6causes:- Hartnup disease- malignant carcinoid syndrome (increased tryptophan metabolism)- isoniazid (decreased B6)What happens if there's a:deficiency:- PELLAGRA: diarrhea, dermatitis, dementia! Death.- the dermatitis: C3/C4 dermatome = circumferential "broad collar" rash [Casal necklace], hyperpigmentation of sun-exposed skin. excess:- facial flushing (induced by prostaglandin, avoid by taking aspirin with niacin)- hyperglycemia- hyperuricemianote:- can be used to treat dyslipidemia, as it lowers levels of VLDL and raises HDL
Vitamin B5alternative name:function:What happens if there's a:deficiency:
alternative name: pantothenic acidfunction:- essential component of coenzyme A and fatty acid synthaseWhat happens if there's a:deficiency: - dermatitis, enteritis, alopecia, adrenal insufficiency
Vitamin B6alternative name:function:What happens if there's a:deficiency: excessdiagnosis:
alternative name: pyridoxinefunction:- converted to pyridoxal phosphate (PLP), a cofactor used in transamination (ALT, AST), decarboxylation reactions, glycogen phosphorylase- needed for synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including 5HT, epi, norE, DA and GABAWhat happens if there's a:deficiency: - convulsions- hyper-irritability- peripheral neuropathy (inducible by isoniazid and OCP)- sideroblastic anemia 2/2 impaired hemoglobin synthesis and iron excessMCC:isoniasid therapyalcoholism
Vitamin B7alternative name:function:What happens if there's a:deficiency:
alternative name: biotinfunction: cofactor for carboxylation enzymes (which add 1-carbon group)-* pyruvate carboxylase (pyruvate to oxaloacetate)- acetyl-coA carboxylase (acetyl-CoA to malonyl-CoA; FA synthesis)- propionyl-CoA carboxylase (propionyl-CoA to methylmalonul-CoA)*Think - biotin..tin can...tin can of pop....tin carb of papWhat happens if there's a:deficiency: - rare, dermatitis, alopecia and enteritis- caused by antibiotic use or excessive ingestion of avidin in raw egg whites (REMEMBER --> AVIDIN binds biotin AVIDLY!)
Vitamin B9alternative name:function:source and storage:What happens if there's a:deficiency: labs/diagnosis:
alternative name: folatefunction:- converted to tetrahydrofolic acid (THF) a coenzyme for 1-carbon transfer/methylation reactions- important for synthesis of nitrogenous bases in DNA and RNAsource and storage:- green leafy vegetables- small reserve primarily in the liver (3-4 mo)What happens if there's a:deficiency: - macrocytic, megaloblastic anemia- glossitis- NO neurologic symptoms (unlike B12)- supplement in pregnancy to decrease incidence of neural tube defectslabs/diagnosis:- increased homocysteine, normal methylmalonic acid- most common vitamin deficiency in US
Vitamin B12 alternative name:function...draw out pathway:source and storage:causes of deficiencyWhat happens if there's a:deficiency: excessdiagnosis:
alternative name: cobalaminefunction:- co-factor for methionine synthase (transfers CH2 groups as methylcobalamine) and methylmalonyl-CoA mutase- only synthesized by microorganismssource and storage:- animal products- large reserve storage in the liver (3-4 yr)causes of deficiency- malabsorption- lack of intrinsic factor (pernicious anemia)- absence of terminal ileum- insufficient intake (veganism)What happens if there's a:deficiency: - macrocytic, megaloblastic anemia- hypersegmented PMNs- paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts and spinocerebellar tracts)- prolonged deficiency can lead to irreversible nerve damageNOTE: can be caused by NO abuse!diagnosis:- anti-intrinsic antibodies is diagnostic for pernicious anemia- increased homocysteine and MMA levels
Vitamin Calternative name:function:source and storage:What happens if there's a:deficiency: -BT, PT, PTT?excess
alternative name: ascorbic acidfunction:- antioxidant- facilitates iron absorption by reducing it to Fe2+ state- necessary for hydroxylation of proline and lysine in collagen synthesis- necessary for dopamine beta-hydroxylase, which converts DA to NEsource and storage:- cirtus fruitWhat happens if there's a:deficiency: - SCURVY: swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, "corkscrew" hair-Defective collagen synthesis -> weak BV walls -> hard for platelet to aggregate -> increased bleeding time-hi BT, normal PT PTT cuz coag cascade not affectedexcess- nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasisNOTE:- can be used as ancillary treatment for methemoglobinemia by reducing Fe3+ to Fe2+
Vitamin Dforms of vitamin D and functions:function:What happens if there's a:deficiency: excessdiagnosis:
forms of vitamin D and functions:- D2 = ergocalciferol, from plants- D3 = cholecalciferol, in milk, formed in sun exposed skin (stratum basale)- 25-OH D3 = storage form- 1,25-(OH)2 D3 (calcitriol) = active form function:- acts to increase intestinal absorption of calcium and phosphate- increases bone mineralization at low levels- increases bone resorption at higher levelsWhat happens if there's a:deficiency: - rickets in children = bone pain and deformity- osteomalacia in adults = bone pain and muscle weakness- hypocalcemic tetany- deficiency is exacerbated by low sun exposure, pigmented skin, prematurity excess:- leads to hypercalcemia and hypercalciuria- loss of appetite, stupor- seen in granulomatous disease (increased activation of vitamin D by epithelioid macrophages)
Vitamin Ealternative name:function:causes:source and storage:What happens if there's a:deficiency:
alternative name: tocopherol/tocotrienolfunction:- antioxidant (protects RBCs and membranes from ROS damage)- alters anticoagulative properties of WarfarinWhat happens if there's a:deficiency: - hemolytic anemia- acanthocytosis- muscle weakness- posterior column and spinocerebellar tract demyelination (similar to B12 deficiency but lacking megaloblastic anemia, hyper-segmented PMNs, or increased MMA levels)
Zincfunction:What happens if there's a:deficiency:
function:- mineral essential for 100+ enzymes activity --> ZINC finger formationWhat happens if there's a:deficiency: - delayed wound healing- hypogonadism- decreased adult hair (axillary, facial, pubic)- dysgeusia- anosmia- acrodermatitis enteropathica (periorbital and acral dermatitis)
Vitamin Kalternative name:function:source and storage:What happens if there's a:deficiency: -BT, PT, PTT
alternative name: phytomenadione, phylloquinone, phytonadionefunction:- cofactor for gamma-carboxylation (by gamma-glutamyl carboxylase) of glutamic acid residues on various proteins required for blood clotting- necessary for clotting cascade factors: II, VII, IX, X and protein C and Ssource and storage:- synthesized by intestinal floraWhat happens if there's a:deficiency: - depletion of vitamin K dependent clotting factors by Warfarin- neonatal hemorrhage with increased PTT and aPTT with normal bleeding time --> give neonates injection of vitamin K to prevent hemorrhagic disease of the new born. Infants are born with low vitamin K stores due to poor transplacental transfer. Their livers are also unable to use vitamin K efficiently and breast milk is low in this vitamin. Other risk factors for neonatal vitamin K deficiency and hemorrhage include refusal of vitamin K ppx at birth and exclusive breast feeding. - also caused by prolonged antibiotic use
alternative name:function:causes:source and storage:What happens if there's a:deficiency: excessdiagnosis:
alternative name:function:causes:source and storage:What happens if there's a:deficiency: excessdiagnosis:
Kwashiorkor Malnutritiondeficiencyfindings
deficiency: protein deficiency!findings: results from a protein deficiency MEAL- Malnutrition- Edema- Anemia- Liver (fatty)
Marasmus Malnutritiondeficiencyfindings
Marasmus Malnutritiondeficiency- total calorie malnutrition findings- emaciation (tissue/muscle wasting) +/- edema- MARasmus results in MUScle wasting
Draw the metabolic pathway of the breakdown of ethanol.What is the metabolic consequence of excess ethanol ingestion?What drug is used to counteract ingestion of ethylene glycol and/or methanol? What is it's mechanism of action?What drug is used to treat alcoholism that results in exacerbating "hangover" symptoms?
What is the metabolic consequence of excess ethanol ingestion?- increased NADH/NAD+ ratio which in turn leads to increased production of lactate, malate and glycol-6-PWhat drug is used to counteract ingestion of ethylene glycol and/or methanol? What is it's mechanism of action?fomepizole (antizol)What drug is used to treat alcoholism that results in exacerbating "hangover" symptoms?disulfuram (antabuse)
Location of metabolic pathways-Mitochondria-Cytoplasm-Both
-Mitochondria: "BATOK" -beta ox of FA, acetyl coa synthesis, TCA cycle, ox phos, ketogenesis-Both - "HUG takes 2" -Heme synthesis, urea, cycle, Gluconeogenesis-Cytoplasm - all others
How are glycolysis and the TCA cycle linked?What is the reaction?What are the 5 co-factors required for the action of this complex?What activates this complex (+) feedback?How does arscenic inhibit this and what are the symptoms of arsenic poisoing?
1) Pyruvate -> Acetyl coa via PDH2) Pyruvate -> OAA via pyruvate Carb.
Pyruvate Dehydrogenase Complex Deficiencywhat is it:possible causesinheritance pattern:findings:treatment:
what is it: causes a buildup of pyruvate that then gets shunted to lactate (via LDH) and alanine (via ALT)Possible causes - arsenic poisoning or vitamin/cofactor deficienyinheritance pattern: x linkedfindings:- neurologic defects- lactic acidosis- increased serum alanine starting in infancytreatment: - increased intake of KETOgenic nurtients (high fat content of increased lysine and leucine)
What are the only purely ketogenic amino acids?
What are the only purely ketogenic amino acids?Lysine and leucine
Draw the TCA cycle. What are the net products of the cycle per acetyl-CoA?What cofactors are required for alpha-ketolgutarate dehydrogenase complex?
What are the net products of the cycle per acetyl-CoA?*3 NADH2 FADH22 CO21 GTP10 ATP*Remember:Officer, Can I keep selling some sex for moneyorCitrateIs (isocitrate)Kreb's (alpha Keto-glutatrate)Starting (succinyl co A)Substance (succinate)For (fumarate)Making (malate)Oxaloacetate
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency)inheritance pattern:pathophysiology of disease:precipitants of diseasePBS findings:
inheritance pattern:- x-linked recessive - most common enzyme deficiency- more prevalent among AA- increased malarial resistancepathophysiology of disease:- NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides- NADPH is generated by the HMP shunt via the action of glucose-6-dehydrogenase- loss of NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents precipitants of disease- oxidizing agents include ie: fava beans, sulfonamides, primaquine, anti-TB drugs)- infections PBS findings:- heinz bodies which are denatured hemoglobin precipitates within RBCs due to oxidative stress- bite cells resulting from phagocytic removal of Heinz bodies by splenic macrophages"Bite into some Heinz ketchup*
Essential fructorsuriametabolic defect:inheritance pattern:symptoms:
metabolic defect:- in fructokinaseinheritance pattern:- autosomal recessivesymptoms:- benign and asymptomatic condition since fructose is not trapped in cells- some fructose appears in blood and urine
Fructose intolerancemetabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.
metabolic defect:- hereditary deficiency of aldolase Binheritance pattern:- autosomal recessivepathophysiology:- F1P accumulates causing a decrease in available phosphate resulting in glycogenolysis and gluconeogenesis - symptoms present following consumption of fruit, juice or honey- note that urine dipstick will be negative but only because it tests for glucose onlysymptoms:- hypoglycemia- jaundice- cirrhosis- vomitingtreatment:- decrease intake of both fructose and sucrose (glucose + fructose)
Galalactokinase deficiencymetabolic defect:inheritance pattern:pathophysiology and symptoms:Draw metabolic pathway involved.
metabolic defect:- deficiency of galactokinaseinheritance pattern: autosomal recessivepathophysiology:- galactitol accumulates if galactose i present in diet- relatively mild conditionsymptoms:- develop when infant begins feeding- galactosemia and galactosuria- infantile cataracts- may also present as failure to track objects or develop a social smileDraw metabolic pathway involved.
Classic Galactosemiametabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.
metabolic defect:- absence of galactose-1-phosphate uridyltransferaseinheritance pattern:- autosomal recessivepathophysiology:- damage due to accumulation of toxic substances, including galactitol which accumulates in the lens of the eyesymptoms:- failure to thrive- jaundice- hepatomegaly- infantile cataracts- intellectual disability- E. coli sepsis in neoantestreatment:- exclude galactose and lactose (galatose + glucose) from dietDraw metabolic pathway involved.
Lactase Deficiencymetabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:
metabolic defect:- insufficient lactase enzyme --> dietary lactose intolerance inheritance pattern:PRIMARY: age dependent decline after childhood due to absence of lactase-persistent allele. Common in asian, african or native americanSECONDARY: loss of brush border due to inflammation, infection (ie: giardiasis), autoimmune disease, etc. note: CONGENITAL DEFICIENCY = rarepathophysiology and symptoms:- lactase functions in the brush border to digest lactose (in human and cow milk) into glucose and galactose --> disruption of the brush border = intolerance- sx include bloating, cramps, flatulence, osmotic diarrheatreatment:- avoid dairy- lactase pills- lactose free milk
Hyperammonemiametabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.
metabolic defect:- inheritance pattern:- can be acquired (liver disease)- or hereditary (urea cycle enzyme deficiency)pathophysiology and symptoms:- excess NH3 which depletes alpha-ketoglutarate leading to inhibition of TCA cycle-Hepatic encephalopathy - liver cannot metabolize AAs -> accumulation of NH3 -> NH3 crosses brain and converts glutamate to glutamine -> low glutamate produces the neuro symptoms- tremor (asterixis)- slurred speech treatment:- limit proteinalso to lower ammonia levels can give :- lactulose (acidifies GI tract to trap NH4+ for excretion)- rifaximin to decrease colonic ammoniagenic bacteria- benzoate, phenylacetate or phenylbutyrate to bind NH4+ and lead to excretion
N-acetylglutamate synthase deficiencymetabolic defect:pathophysiology and symptoms:
N-acetylglutamate synthase deficiencymetabolic defect:- absence of N-acetylglutamate (required cofactor for carbamoyl phosphate synthetase I) leading to hyperammonemiapathophysiology and symptoms:- presents in neonates as poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability- identical to carbamoyl phopshate synthetase I deficiency
Ornithine transcarbamylase deficiencymetabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.
metabolic defect:- most common urea cycle disorderinheritance pattern:- x linked recessive (all other urea cycle enzyme deficiencies are autosomal recessive)pathophysiology- interferes with body's ability to eliminate ammonia- often evidence in first few days of life but may present later- excess carbamoyl phosphate is converted to orotic acid symptoms:- increased orotic acid in blood and urine- decreased BUN- symptoms of hyperammonemia- NO megaloblastic anemia (vs orotic aciduria)treatment:Draw metabolic pathway involved.-cant convert ornithine to citruluine in the TCA cycle
Phenylketouriametabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.How does this compare to maternal PKU?pathophys:symptoms:
metabolic defect:- decreased phenylalanine hydroxylase OR- decreased tetrahydrobiopeterin cofactor (malignant PKU)- either way, TYROSINE becomes essential (must be obtained through diet)inheritance pattern:- autosomal recessive- 1:10,000 births- screening is done 2-3 days after birth, as it is normal at birth due to maternal enzymes during fetal lifepathophysiology and symptoms:- build up of phenylketones (phenylacetate, phenyllactate, phenylpyruvate)treatment:- MUST avoid aspartame which contains phenylalanineDraw metabolic pathway involved.How does this compare to maternal PKU?pathophys: lack of proper dietary therapy during pregnancy-The mom has PKU not the childsymptoms: (in infant)- intellectual disability- growth retardation- microencephaly- congenital heart defects
Maple Syrup Urine Diseasemetabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:
metabolic defect:- blocked degradation of BRANCHED amino acids (Isoleucine, Leucine, Valine) due to decreased branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) or B1 deficiency"I Love Vermont maple syrup from branched maple trees"inheritance pattern:- autosomal recessivepathophysiology and symptoms:- increased alpha-keto acids in the blood, especially those of leucine which are NEUROTOXIC --> resulting in SEIZURES, irritability, lethargy, and poor feeding- urine smells like maple syrup/burnt syrup due to metabolite of isoleucinetreatment:- restriction of isoleucine, leucine and valine in diet + thiamine supplementation- remember that branched-chain alpha-ketoacid dehydrogenase complex requires 5 co-factors ("Tender Loving Care for Nancy")1. Thiamine2. Lipoate3. Coenzyme A4. FAD5. NAD
Alkaptonuriametabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:
metabolic defect:- congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate inheritance pattern:- autosomal recessivepathophysiology and symptoms:- leads to pigment forming homogentistic acid accumulating in the tissue- usually benign - findings include blue-black connective tissue and sclerae (ochronosis)- urine turns BLACK on prolonged exposure to air- may have debilitating arthralgias (homogentistic acid is toxic to cartilage)
Draw the metabolic pathway involved in alkaptonuria
- congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate leading to pigment forming homogentistic acid accumulating in the tissue
Homocystinuriametabolic defect:inheritance pattern:pathophysiology and symptoms:treatment:Draw metabolic pathway involved.
metabolic defect:there are three different types, all of which result in excess homocysteine- cystathionine synthase deficiency -will have Hi met and homo (RX: less methionine, increase cysteine, B12 and folate)- decreased affinity for cystathionine synthase for pyridoxal phosphate (RX: increased B6 and cysteine in diet)- methionine synthase (homocysteine methyltransferase) deficiency -Will have hi homo and low met(RX: increased methionine in diet)inheritance pattern:- all autosomal recessive pathophysiology and symptoms:- all result in XS homocysteine- increased homocysteine in urine- intellectual disability- osteoporosis- marfanoid habitus- kyphosis- lens sublaxation (downward and inward)- thrombosis- atherosclerosis (stroke and MI)treatment:Draw metabolic pathway involved.
Cystinuriametabolic defect:inheritance pattern:pathophysiology and symptoms:diagnostic testtreatment:Draw metabolic pathway involved.
metabolic defect:- hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine and Arginine (COLA)- note CYSTINE is made of 2 cysteines connected by a disulfide bondinheritance pattern:- autosomal recessive- 1:7000pathophysiology and symptoms:- excess cystine in urine can lead to recurrent precipitation of HEXAGONAL CYSTINE STONESdiagnostic test- urinary cyanide-nitroprusside testtreatment:- urinary alkalization (ie potassium citrate, acetazolamide) and chelating agents (penicillamine) increasing the solubility of cystine stones- hydrationDraw metabolic pathway involved.
What is the general pathophysiology behind glycogen storage diseases?What are the 4 autosomal recessive types of glycogen storage diseases? What are their names?
What is the general pathophysiology behind glycogen storage diseases?*- all result in abnormal glycogen metabolism and accumulation of glycogen within cells- PERIODIC-ACID-SCHIFF (PAS) stain identifies glycogen and is useful in identifying these diseasesWhat are the 4 autosomal recessive types of glycogen storage diseases? What are their names?*- "Very Poor Carbohydrate Metabolism" = V, P, C, M- VON GIERKE DISEASE (TYPE I)- POMPE DISEASE (TYPE II)- CORI DISEASE (TYPE III)- MCARDLE DISEASE (TYPE V)*
Von Gierke Diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- glycogen storage disease (type I)inheritance pattern:- autosomal recessivefindings:- severe fasting hypoglycemia- increased glycogen in liver- increased blood lactate- increased triglycerides- increased uric acid (Gout)deficient enzyme:- glucose-6-phosphatecomments:- frequent oral glucose/cornstarch- avoid fructose and galactose- impaired gluconeogenesis and glycogenolysis
Pompe Diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- glycogen storage disease, type IIinheritance pattern:- autosomal recessivefindings:- cardiomegaly- hypertrophic cardiomyopathy- exercise intolerance- systemic findings leading to early deathdeficient enzyme:- lysosomal alpha-1,4-glucosidase with alpha-1,6-glucosidase activity(acid maltase)comments:"Pompe trashes the Pump" (heart, liver, muscles)
Cori Diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- glycogen storage disease, type III- milder version of type Iinheritance pattern:- autosomal recessivefindings:- normal lactate levels- accumulation of limit dextrin-like structures in cytosoldeficient enzyme:- debranching enzymes (alpha-1,6-glucosidase)comments:- gluconeogenesis is intact
McArdle Diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- glycogen storage disease, type Vinheritance pattern:- autosomal recessivefindings:- increased glycogen in muscle but muscle cannot break it down leading to --> painful MUSCLE cramps- MYOGLOBINURIA (red urine) with strenuous exercise- arrthymthia 2/2 electrolyte abnormalitie- second wind phenomenon during exercise due to increased muscular blood flowdeficient enzyme:- skeletal muscle glycogen phosphorylase (MYOphosphorylase)comments:- blood glucose levels typically unaffected- McARDLE = MUSCLE
Fabry Diseasetype of disease:inheritance pattern:findings:deficient enzyme:accumulated substrate:comments:
type of disease:- lysosomal storage disease of sphingolipidosisinheritance pattern:- X-linked recessivefindings:- early: triad of episodic peripheral neuropathy, anigokeratomas, hypohidrosis- late: progressive renal failure, cardiovascular diseasedeficient enzyme:- alpha-galactosidase Aaccumulated substrate:- ceramide trihexoside
Gaucher Diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- lysosomal storage disease of sphingolipidosis (most common)inheritance pattern:- autosomal recessive findings:- hepatosplenomegaly- pancytopenia- osteoporosis- aseptic necrosis of femur- bone crises- Gaucher cell (lipid-laden macrophages resembling crumpled tissue paper)deficient enzyme:- glucocerebrosidase (beta-glucosiade)comments:- treat with recombinant glucocerebrosidase
Niemann-Pick diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- lysosomal storage disease of sphingolipidosisinheritance pattern:- autosomal recessivefindings:- progressive neurodegeneration- hepatosplenomegaly- foam cells (lipid laden macrophages)- "cherry-red" spot on maculadeficient enzyme:- sphingomyelinasecomments:- accumulates sphingomyelin"No man picks [Niemann-Pick) his nose with his sphinger (spingomyelinase)"
Tay-Sachs diseasetype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- lysosomal storage disease of sphingolipidosisinheritance pattern:- autosomal recessivefindings:- progressive neurodegeneration- developmental delay- cherry red spot on macula- lysosomes with onion skin- NO hepatosplenomegalydeficient enzyme:- hexosaminindase Acomments:- accumulates GM2 ganglioside- "Tay SaX lacks heXosaminidase"
Krabbe Diseasetype of disease:inheritance pattern:findings:deficient enzyme:
type of disease:- lysosomal storage disease of sphingolipidosisinheritance pattern:- ARfindings:- peripheral neuropathy- developmental delay- optic atrophy- globoid cellsdeficient enzyme:- galactocerebrosidase leading to galactocerebroside accumulation
Metachromatic leukodystrophytype of disease:inheritance pattern:findings:deficient enzyme:
type of disease:- lysosomal storage disease of sphingolipidosisinheritance pattern:- ARfindings:- central and peripheral demyelination with ataxia, dementiadeficient enzyme:- arysulfatase A resulting in cerebroside sulfate accumulation
Hurler Syndrometype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- lysosomal storage disease of mucopolysaccharidosesinheritance pattern:- ARfindings:- developmental delay- gargoylism- airway obstruction- corneal clouding- hepatosplenomegalydeficient enzyme:- alpha-L-iduronidase leading to build up of heparan sulfate and dermatan sulfatecomments:
Hunter Syndrometype of disease:inheritance pattern:findings:deficient enzyme:comments:
type of disease:- lysosomal storage disease of mucopolysaccharidosesinheritance pattern:- XRfindings:- milder version of hurler syndrome + aggressive behavior- no corneal cloudingdeficient enzyme:- iduronate sulfatase leading to build up of heparan sulfat and dermatan sulfatecomments:
What are the ketone bodies? What are the signs of ketone production?Where are they produced?Describe the basic pathophysiology of ketosis in starvation and diabetic ketoacidosis and alcoholics
What are the ketone bodies? What are the signs of ketone production?- ketone bodies = acetone, acetoacetate and beta-hydroxybutyrate- breath smells like acetone (fruity odor)- urine test for ketones can detect acetoacetate but not beta-hydroxyhutyrateWhere are they produced?- in the liver, fatty acids and amino acids are metabolized to acetoacetate and beta-hydroxybutyrate (to be used in the brain and muscle)Describe the basic pathophysiology of ketosis in starvation and diabetic ketoacidosis. - in both states, oxaloacetate is depleted for gluconeogenesis- both processes cause a buildup of acetyl-CoA which shunts glucose and FFA toward the production of ketone bodies-Alcohol leads to excess NADH, which shunts OAA to malate leading to OAA depletion and same as above
What is the definition of a calorie?Metabolism of the following amounts of dietary stuff yields how many calories of energy?1 g of protein or carbohydrate =1 g of fat = 1 g alcohol =
What is the definition of a calorie?1. the energy needed to raise the temperature of 1 gram of water through 1 °C (now usually defined as 4.1868 joules).2. the energy needed to raise the temperature of 1 kilogram of water through 1 °C, equal to one thousand small calories and often used to measure the energy value of foods.1 g of protein or carbohydrate = 4 kcal (4 CALORIES)1 g of fat = 9 kcal (9 CALORIES)1 g alcohol = 7 kcal (7 CALORIES)paf = 479
What are the priorities of the bodies in states of fasting and starvation?For each of the following states, describe the primary metabolic processes supplying the body with energy and the "signaling" molecules responsible for the process. FED STATE (after a meal)FASTING (between meals)STARVATION (day 1-3)STARVATION (after day 3)
What are the priorities of the bodies in states of fasting and starvation?- supplying the brain and RBCs with sufficient glucose and to preserve proteinFor each of the following states, describe the primary metabolic processes supplying the body with energy and the "signaling" molecules responsible for the process. FED STATE (after a meal):process: glycolysis and aerobic respirationsignaling: insulin, stimulates the storage of lipids, proteins and glycogenFASTING (between meals)process: hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor)signaling: glucagon and epinephrine stimulate use of fuel reservesSTARVATION (day 1-3)process: blood glucose levels maintained by- hepatic glycogenolysis- adipose release of FFA- muscle and liver, which shift fuel use from glucose to FFA- hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA - the only triacylglycerol components that contribute to gluconeogenesis NOTE: glycogen reserves are depleted after day 1. AND RBCs LACK mitochondria and therefore cannot use ketones. STARVATION (after day 3)process: - adipose stores (ketone bodies become the main source of energy for the brain). once these are depleted, vital protein degeneration accelerates, leading to organ failure and death- amount of excess stores determines survival time
What cellular components/biomolecules are cholesterol important for? What is the process by which cholesterol is synthesized and what is the rate limiting step?How do statins function?
What cellular components/biomolecules are cholesterol important for?- needed to maintain cell membrane integrity as well as synthesize bile acid, steroids and vitamin DWhat is the process by which cholesterol is synthesized and what is the rate limiting step?- rate limiting step is that catalyzed by HMG-CoA reductaseHow do statins function?- statins act to competitively and reversibly inhibit HMG-CoA reductase
Draw the pathway by which dietary fat and cholesterol are absorbed in the gut and then are processed by the liver and shutting to peripheral tissues. For the following enzymes, name the molecule they are responsible for degrading and the primary site of their action. Pancreatic lipaseLipoprotein lipase Hepatic TG lipaseHormone-sensitive lipaseLCATcholesterol ester transfer protein
For the following enzymes, name the molecule they are responsible for degrading and the primary site of their action. Pancreatic lipase: decrease TGs in small intestineLipoprotein lipase: degrades TGs circling in chylomicrons and VLDLS. found on vascular endothelial surfacesHepatic TG lipase: degradation of TGs remaining in IDLHormone-sensitive lipase: degradation of TGs stored in adipocytesLCAT: catalyzes the esterification of cholesterolcholesterol ester transfer protein: mediates transfer of cholesterol esters to other lipoprotein particles
Familial Dyslipidemia (type I)inheritance pattern:pathogenesis:what is increased in blood:clinical findings:
inheritance pattern: ARpathogenesis: lipoprotein lipase OR apolipoprotein C-II deficiencywhat is increased in blood: chylomicrons, TG, cholesterolclinical findings: - pancreatitis- hepatosplenomegaly- eruptive/pruritic xanthomas (no increased risk for atherosclerosis)- creamy layer in supernatant
Familial hypercholesterolemiainheritance pattern:pathogenesis:what is increased in blood:clinical findings:
inheritance pattern: ADpathogenesis:- absent or defective LDL receptorswhat is increased in blood:- LDL, cholesterolclinical findings:- heterozygotes (1:500) have cholesterol = 300 mg/dl- homozygotes (very rate) cholesterol = 700+ mg/dl- accelerated atherosclerosis (MI before 20)- tendon (achilles) xanthomas- corneal acrus
Hypertriglyceridemia (type IV) inheritance pattern:pathogenesis:what is increased in blood:clinical findings:
inheritance pattern: ADpathogenesis:- hepatic overproduction of VLDLwhat is increased in blood:- VLDL, TGclinical findings:- hypertriglyceridemia (> 1000 mg/dl)- can cause acute pancreatitis