Flashcards in Biochem 2 USMLE Deck (196):
underproduction of heme causes this type of anemia
accumulations of heme intermediates causes thius
this type of porphyria inhibits ferrochelatase and ALA dehydrase. Cooproporphyrin and ALA accumulate in the urine
this type of porphyria results from a deficiency in uroporphyrinogen I synthetase. Porphobilogen and delta-ALA accumulate in urine
Acute intermittent porphyria
this type of porphyria results from a deficiency in uropophyrinogen decarboxylase. Uroporphyrin accumulates in urine (tea-colored). results in photosensitivity
Porphyria cutanea tardia
symptoms of porphyrias (5 Ps)
Precipitated by drugs
heme is scavenged from RBCs and ____ is reused
bilirubin is toxic to this organ system
bili is transported by this protein
bili is removed from the blood by this organ
bili is conjugated with this ____
bili is excreted in this supstance
where in the body is bili processed into its excreted form
some ________, an intestinal intermediate, is reabsorbed into blood and excreted as urobilin into urin
this poison has a 200x greater affinity than O2 for HGB
hemoglobin is composed of 4 polypeptide subunits. describe them
HGB exists in 2 forms what are they
T (taut) low affinity for O2
R (relaxed) high affinity for O2 (300x)
Hgb exibits _______ cooperativity and ________ allostery (accounts for the sigmoid-shaped O2 dissociation curve for hgb), unlike myoglobin
name the things that favor the relaxed form of hgb (shifting dissociation curve to the right, leading to O2 unloading)
increased Cl-,H+,CO2,2,3BPG, hight temp.
mneu: when you're relaxed, you do your job better (carry O2)
what are the fetal hgb subunits
fetal hgb has a lower affinity for _____ than adult hgb and thus has a higher affinity for O2
Iron in hgb is in a _____ state (ferrous, Fe++)
this is an oxidized form of hgb (ferric, Fe++) that does not bind O2 as readily but has increased affinity for CN-.
administer this in cyanide poisoning to oxidize hgb to methemoglobin form
tx toxic levels of METHemoglobin with -----
CO2 is transported in the blood by binding to
amino acids in the globin chain (at N terminus) but not to heme
CO2 binding favors this form of hgb (and thus promotes O2 unloading)
CO2 must be transported from tissue to lungs, the reverse of O2, and this occurs primarily in what form
this is a molecular biology laboratory procedure that is used to synthesize many copies of a desired fragment of DNA
polymerase chain reaction (PCR
steps of PCR
1) DNA is denatured by heating to generate 2 separate strands
2)during cooling, excess premade DNA primers anneal to a specific sequence on each strand to be amplified
3) heat-stable DNA polymerase replicates the DNA sequence following each primer
These steps are repeated multiple times for DNA sequence aplification
In this molecular biology technique, a DNA sample is electrophoresed on a gel and then transferred to a filter. The filter is then soaked in a denaturant and subsequently exposed to a labeled DNA probe that recognizes and anneals to its complementary strand. The resulting double stranded labeled piece of DNA is visualized when the filter is exposed to film.
this molecular biology technique, is a similar technique, except that it involves radioactive DNA probe binding to sample RNA
In this molecular biology technique, sample protein is separated via gel electrophoresis and transferred to a filter. Labeled antibody is used to bind to relevant PROTEIN
in this method of testing, a pts blood sample is probed with either:
1)test Ag (coupled to color-generating enzyme)-to see if immune system recognizes it; or
2) Test Ab (coupled to color generating enzyme) to see if certain Ag is present
If the target subsance is present in the sample, the test solution will have an intense color reaction, indicating a positive test result.
Enzyme-linked immunosorbent assay (ELISA)
ELISA is used in many labs to determine whether a particular ___(e.g., anti-HIV) is present in a pts blood sample. Both the sensitivity and specificity of ELISA approach 100% but both false positive and false negative results do occur
define the genetic term VARIABLE EXPRESSION
nature and severity of the phenotype varies from 1 individual to another
define the genetic term INCOMPLETE PENETRANCE
Not all individuals with a mutant genotype show the mutant phenotype
define the genetic term PLEIOTROPY
1 gene has >1 effect on an individual's phenotype
define the genetic term IMPRINTING
differences in phenotype depend on whether the mutationis of maternal or paternal origin (e.g., AngelMan's syndrome [Maternal], Prader-Willi syndrome [Paternal]
define the genetic term ANTICIPATION
Severity of dz worsens or age onset of dz is earlier in succeeding generations (e.g., Huntington's dz)
define the genetic term LOSS OF HETEROZYGOSITY
If a pt inherits or develops a mutation in a tumor suppressor gene, the complimentary allele must be deleted/mutated before CA develops. This is not true of oncogenes
define the genetic term DOMINANT NEGATIVE MUTATION
exerts a DOMINANT EFFECT. A heterozygote produces a nonfxnl altered protein that also prevents the normal gene product from funcioning
define the genetic term LINKAGE DISEQUILIBRIUM
Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in a population, not in a family, and often varies in different populations
define the genetic term MOSAICISM
occurs when cells in the body have different genetic makeup (e.g. lyonization--random X inactivation in females)
define the genetic term LOCUS HETEROGEITY
Mutations at different loci can produce the same phenotype (e.g., albinism
Hardy-Weinberg law assumes (4)
1) there is no mutation occurring at the locus
2) there is no selection for any of the genotypes at the locus
3) Mating is completely random
4) There is no migration into or out of the population
If a population is in Hardy-Weinberg equilibrium. p and q are separate allele. 2pq=heterozygote prevalence.
allele prevalence is?
disease prevalence is?
p2 + 2pq +q2 =1
this mode of inheritance looks like this [p.107]
Often due to defects in sxl genes. Many generations, both male and female, affected. It is often pleiotropic and, in many cases, present clinically after puberty. Family hx is crucial to dx
this mode of inheritance looks like this [p.107]
25% of offspring from 2 carrier parents are affected. Often due to enzyme deficiencies. Usually seen in only 1 generation. Commonly more severe. Pts often present in childhood.
this mode of inheritance looks like this [p.107]
Sons of heterozygous mothers have a 50% chance of being affected. No male-to-male transmission. Commonly more severe in males. Heterozygous females may be effected.
X linked recessive
this mode of inheritance looks like this [p.107]
transmitted through both parents. Either male or female offspring of the affected mother may be affected, while ALL female offspring of the affected father are diseased. e.g., Hypophosphatemic rickets.
X linked dominant
this mode of inheritance looks like this [p.107]
transmitted only through mother. All offspring of affected females may show signs of dz. e.g., Leber's hereditary optic neuropathy.
This autosomal dominant dz, is ALWAYS BILATERAL, there is a massive enlargement of kidneys due to multiple large cysts. Pts present with pain, hematuria, hyperension, progressive renal failure. 90% of cases are due to mutation in APKD1 (chromosome 16). Associated w/ polycystic liver dz, berry aneurysms, mitral valve prolapse. Juvenile form is recessive
Adult Polycystic Kidney Dz
This autosomal dominant dz, is characterized by elevated LDL owing to defective or absent LDL receptor. Heterozygotes (1:1500) have cholesterol~300mg/dl. Homozygotes (very raare) have cholesterol ~700+mg/dl, severe atherosclerotic dz early in life, and tendon xanthomas (classically in the Achilles tendon); MI may develop before age 20.
Familial hypercholesterolemia (hyperlipidemia type IIA)
This fibrillin gene mutation results in connective tissue disorders. It results in skeletal abnormalities--tall with long extremities (arachnodactylyl), hyperextensive joints, and long, tapering fingers and toes.
CV--cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms. Floppy mitral valve.
Ocular-subluxation of lenses
This autosomal dominant dz, is characterized by cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal d/o (e.g., scoliosis), pheochromocytoma, and increased tumor suceptibility. On long arm of chromosome 17
Neurofibromatosis type 1 (von Recklinghausen's dz)
mneu: chrom 17-17 letters in von Recklinghausen
This autosomal dominant dz, is characterized by bilateral acoustic neuroma, optic pathway gliomas, juvenile cataracts.
Neurofibromatosis type 2
Neurofibromatosis type 2 is on this gene on this chromosome
NF2 gene on chrom 22
This autosomal dominant dz, is characterized by facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardiac rhabdomyomas. Incomplete penetrance, variable presentration.
This autosomal dominant dz, is characterized by hemangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.
Von Hippel-Lindau dz
Von Hippel-Lindau dz is associated with deletion of this gene on this chromosome
VHL gene (tumor suppressor) on chromosome 3 (3p)
mneu: VHL=3 words=chrom 3
This autosomal dominant dz, is characterized by depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of GABA and ACH in the brain. Symptoms manifest in affected individuals between the ages of 20 and 20.
Huntington's dz gene is located on this chromosome. It is a _____ repeat d/o
mneu: "Hunting 4 food"
This autosomal dominant dz, is characterized by the colon becoming covered with adenomatous polyps after puberty. Progresses to cancer unless resected.
familial adenomatous polyposis
familial adenomatous polyposis is a deletion of this chromosome
mneu: 5 letters in "polyp"
This autosomal dominant dz, is characterized by spheroid erythrocytes; hemolytic anemia; increased MCHC. Splenectomy is curative
This autosomal dominant dz, is characterized by autosomal-dominant cell-signaling defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism; short limbs; but head and trunk are normal size
name 5 autosomal-recessive dzs
CF, albinism, alpha1 antitrypsin deficiency, PKU, thalassemias, sickle cell anemia, glycogen storage dz, mucopolysaccharidosis (except Hunter's), sphingolipidosies (except Fabry's), infant polycystic kidney dz, hemochromatosis
CF has this inheratance
what is the gene and chromosome of CF
CFTR on chromosome 7
what is the defective channel in CF that results in secretion of abnormally thick mucus that plugs lungs, pancreas, and liver.
the recurrent pulmonary infections in CF are often due to these 2 bugs
pseudomonas and S. aureus.
this CF complication results in malabsorption and steatorrhea
CF can cause this in this in newborns
how do you dx CF
incresed concentration of Cl-ions in a sweat test.
CF can cause this in males due to absent vas deference
these vitamen deficiencies can be present in CF. It may present as failure to thrive in infancy
CF is the most common lethal genetic dz in this racial group
in CF this tx will loosen mucous plugs
Give 5 X-linked recessive disorders
fragile X, duchenne's muscular dystorphy, hemophilia A & B, Fabry's, G6PD deficiency, Hunter's syndrome, ocular albinism, Lesch-Nyhan syndrome, Bruton's agammaglobinemia, Wiskott-Aldrich syndrome
T or F. Female carriers of X-linked recessive d/o are rarely affected because of random inactivation of X chromosomes in each cell
In this X-linked d/o that begins before 5 y/o, weakness begins in the pelvic girdle muscles and progresses superiorly. YOu may see pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle; cardiac myopathy. Often times kids will use the Gower's manuver, requiring assistance of the upper extremities to stand up, is characteristic (indicates proximal lower limb weakness)
Duchenne's muscular deficiency
Duchenne's muscular deficiency is an X linked d/o that results from a frame-shift mutation that deletes this gene which leads to accelerated mm breakdwon.
mneu: Duchenne's = Deleted Dystrophin
In this d/o the mutation of the dystrophin gene is less sever than Duchenne's
fragile x syndrome is an x-linked defect affecting the methylation and expression of the ____ gene
how common is fragile X
2nd most common cause of mental retardation
most common cause is down sydnrome
give some PE findings of fragile X
macro-orchidism (enlarged testes), long face w/ large jaw, large everted ears, and autism
mneu: Fragile X=eXtra-large testes, jaw, ears
fragile X syndrome is a ______ repeat d/o (CGC)n that may show genetic anticipation (germlike expansion in females).
Give 3 trinucleotide repeat expansion dz
HUNTINGton's dz, MYotonic dystrophy, FRIEDreich's ataxia, frafile X syndrome.
mneu: TRY (trinucleotide) HUNTING for MY FRIED eggs (X)
trinucleotide repeat expansion dz may show this which refers to increased disease severity and age of severity in successive generations
Give 5 common congenital malformations
1) heart defects
3) cleft lip
4) congenital hip dislocation
5) spina bifida
7) Pyloric stenosis
this common congenital malformation is associated with projectile vomiting
give 3 autosomal trisomies
give the genetics of Down syndrome
how common is down syndrome
most common chromosomal d/o and cause of congenital mental retardation
give some physical exam findings of down syndrome
mental retardation, flat facial profile, prominant epicathal folds, simian crease, duodenal atresia, congenital heart dz (most common malformation is septum primum-type ASD due to endocardial cushion defects).
what dzs are people w/ down syndrome at risk for as they get older
alzheimer's dz (>35 y/o)
increase risk of ALL
give tips off in utero that a baby may be trisomy 21
decreased levels of alpha fetoprotein, inceased levels of beta hCG, increased nuchal translucency
95% of cases of trisomy 21 are due to this type of nondisjxn of homologous chromosomes
4% of cases due to robertsonian translocation
1% due to Down mosaicism (no maternal association)
What is the risk of down syndrome in women < 20 y/o?
children with this autosomal trisomy have severe mental retardation, rocker bottom feet, low-set ears, micrognathia (small jaw), congenital heart dz, clenched hands, prominent occiput. Death usually occcurs within 1 year of birth
mneu: Election age (18)
children with this autosomal trisomy have severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain sxs, polydactyly, congenital heart dz. Death usually occurs w/in 1 year of birth
mneu: Pubety (13)
findings of this d/o include microcephaly, severe mental retardation, high ptiched crying/mewing, epicanthal folds, cardiac abnormalities
what is the congenital deletion
short arm of chromosome 5
(46,XX or XY, 5p)
Cleft palate, Abnormal facies, Thymic aplasia (T-cel deficiency), Cardiac defects, Hypocalcemia (secondary to parathyroid aplaisia)
22q11 has variable presentation as these 2 syndromes
DiGeorge Sydnrome (thymic, parathyroid, and cardiac defects) or velocardiofacial syndrome (palate, facial, and cardiac defects)
what are the fat soluble vitamens
this fat soluble vitamen is key in vision
this fat soluble vitamen is key for bone calcification and Ca+ homeostasis
this fat soluble vitamen is key in clotting
this fat soluble vitamen is a key antioxident
this water soluble viatamen is key for blood and neural development
this fat soluble vitamen is key for the CNS and blood
the absorption of fat soluble vitamens is dependent on these 2 organs
gut(ilium) and pancreas
is toxicity more common in water soluble or fat soluble vitamens
malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake can cause these vitamin deficiencies
Water soluble vitamens all wash out easily from the body except this vitamen that is stored in the liver
riboflavin: FAD, FMN
pt presents with dermatitis, glossitis, and diarrhea. What vit deficiencies
this vitamen is a constituent of visual pigments (retinal)
mneu: RETINOL is vitamen A, so think RETIN-A (used topically for wrinkles and acne)
give 3 symptoms of vit A deficiency
night blindness, dry skin, impared immune response
give 3 symptoms of vit A excess
arthralgias, fatigue, headaches, skin changes, sore throat, alopecia
this vitamen fxs in thiamine pyrophosphate, a cofactor for oxidative carboxylation of alpha-keto acids (pyruvate, alpha ketogluterate) and a cofactor for transketolase in the HMP shunt
vitamen B1 (thiamine)
give 2 conditions that can result from vit B1 (thiamine) deficiency
Beriberi and Wernicke-Korsakoff syndrome
this type of beriberi is characterized by polyneuritis and mm wasting
this type of beriberi is characterized by high-output cardiac failure (dilated cardiomyopathy, edema
this vitamen is a cofactor in oxidation and reduction (e.g., FADH2)
vitamen B2 (riboflavin)
give a few signs of vit B2 (riboflavin) deficiency
angular stomatitis, cheilosis, corneal vasculation
mneu: the 2 C's
FAD & FMN are derived from this vitamen
this vitamen is a constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan using vit B6
vitamen B3 (niacin)
give the 3 Ds of Pellagra
diarrhea, dermatitis, dementia (also beefy glossitis)
deficiency of vit B3 (niacin can be caused by hartnup dz. Why?
decreased tryptophan absorption
deficiency of vit B3 (niacin can be caused by malignant carcinoid syndrome. Why?
increased tryptophan metabolism
deficiency of vit B3 (niacin can be caused by INH. Why
decrease vit B6
NAD is derived from _______
this vitamne fxs as a constituent of CoaA (a cofactor for acyl transfors) and component of fatty acid synthase.
vitamen B5 (pantothenate)
mneu: Pantothen-A is in CoA
give some signs of vit B5 deficiencies
dermatitis, enteritis, alopecia, adrenal insufficiency
this vitamen fxs converted to pyridoxal pyridoxal phosphate, a cofactor used in transamination (e.g., ALT & AST), decarboxylation, and heme synthesis
vitamen B6 (pyridoxine)
give signs of vit B6 (pyridoxine)
convulsions, hyperirritability (deficiency inducible by INH and oral contraceptives), peripheral neuropathy.
this vitamen is a cofactor for homocysteine methylation (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA handling.
vitamin B12 (cobalamin)
vitamen B12 is stored primarily in this organ
vitamme B12 is synthesized only by microorganisms and is found only in this type of food
vitamen B12 is usually caused by malabsorption-- give a few examples
sprue, enteritis, Diphyllobothrium latum
vitamen B12 can be caused by pernicious anemia which is caused by a lack of this
vit B12 can be caused by absense of terminal ileum for example in this GI dz
this test is used to detect vit B12
abnormal myelin is seen in B12 deficiency, possibly due to decreased_______ or increased ________ (from metabolism of accumulated methylmalonyl-CoA)
this is the most common vitamen deficiency in the US
this vit fxs in coenzyme (tetrahydrofolate) for 1 carbon transfer, involved in methylation reactions. It is important for synthesis of nitrogenous bases in DNA and RNA
give some signs and symptoms of folic acid deficiencies
macrocytic, megaloblastic anemia (often no neuro symptoms, as opposed to vitB12
what kind of foods are high in folate
green leafy veggies
mneu: FOLate from FOLiage
supliment folic acid when
early pregnancy-reduces neural tube defects
PABA is the folic acid precursor in bacteria. these antimicrobials work because they are PABA analogs
sulfa drugs and dapsone
this vitamen is a cofactor for carboxylations:
1) Pyruvate ->oxaloacetate
2) Acetyl-CoA ->malonyl-CoA
3) Proprionyl-CoA ->methhylmalonyl CoA
biotin deficiency can be caused by using these drugs or eating these
mneu: AVIDin in egg whites AVIDly binds biotin
give some symptoms of biotin deficiency
give some signs of vit C deficiency
scurvy--swollen gumbs, bruising, anemia, poor wound healing
vit C is necessary for hydroxylation of _____ and _____ in collagen synthesis
mneu: vit C Cross-links collagen. British sailors carried limes to prevent scury (origin of word "limey"
vit C facilitates absorption of this nutrient
(keeps it in a reduced state-more absorpable)
vit C is necassary as a cofactor for dopimine in conversion to this neurotransmitter
this is the form of vit D found in milk
this is the form of vit D formed in sun-exposed skin
this is the storage form of vit D
this is the active form of vit D
give some signs of vit D deficiency
rickets in children (bending bones), osteomalacia in adults (soft bones) and hypocalcemic tetany
what is the fx of vit D
increase intestinal absorption of Ca++ & phosphate
what are some signs of vit D excess
hypercalcemia, loss of appetite, stupor.
what dz might you see excess vit D in
(dz where epitheliod macrophages convert vitD into its active form
vit E deficincy results in a fragility of these blood cells
mneu: vit E is for Erythrocytes
what is the fx of vit E
it is an antioxidant that protects erythrocytes from hemolysis
this vitamen funcitons to catalyze gamma-carboxylation of glutamic acid residues on various proteins concerned with blood clotting.
mneu: K is for Koagulation
How is vit K synthesized. What drugs can cause vitK deficiency
prolonged use of broad spectrum antibiotics
vit K deficiency can result in this problem in neonates (what would PT, PTT, & bleeding time be)
neonatal hemorrhage w/ increased PT and increased aPTT but normal bleeding time
what are the vit K dependent clotting factors
II,VII,IX,X and protein C & S
this drug is a vitK antagonist
give a few signs of zinc deficiency
delayed wound healing, hypogonadism, decreased axillary, facial, and pubic hair. It may predispose to alcoholic cirrhosis.
this enzyme catalyzes EtOh to acetaldehyde and reduces NAD+ to NADH
this enzyme catalyzes acetaldehyde to Acetate and reduces NAD+ to NADH
what is the limiting reagent in etoh metabolism
what is the kinetics of alcohol dehydrogenase
how does disulfram (antabuse)work.
inhibits acetaldehyde dehydrogenase--acetaldehyde accumulates contributing to hangover symptoms
describe ethanol hypoglycemia
ethanol metabolism increases NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate, thereby inhibiting gluconeogenesis and leading to hypoglycemia.
altered NADH/NAD+ ratio in the liver is responsible for this change seen in chronic alchololics
hepatic fatty change (hepatocellular steatosis)-shunting away from glycolysis and toward fatty acid synthesis
this is protein malnutrition resulting in skin lesions, edema, liver malfxn (fatty change). Clinical picture is a small child w/ a swollen belly
mneu: resutls from a protein deficient MEAL