Flashcards in One Word_Biochemistry Deck (148):
(found in death cap mushrooms) inhibits RNA polymerase II. Causes liver failure if ingested
Function: Essential for the activity of 100+ enzymes. Important in the formation of zinc fingers (transcription factor motif) Deficiency: Delayed wound healing, hypogonadism, ↓ adult hair (axillary, facial, pubic), dysgeusia, anosmia. May predispose to alcoholic cirrhosis.
Type IV collagen (3)
Basement membrane or basal lamina (maybe lens?)
Type III collagen - Reticulin (5)
skin, blood vessels, uterus, fetal tissue, granulation tissue
Type II collagen (3)
Cartilage (including hyaline), vitreous body, nucleus pulposus
Type I collagen (7)
Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair
Trinucleotide repeat expansion diseases
Huntington's disease = (CAG)n Myotonic dystrophy = (CTG)n Fragile X syndrome = (CGG)n Friedreich's ataxia = (GAA)n
Treatment: Pyruvate dehydrogenase deficiency
Lysine and Leucine - the only purely ketogenic amino acids
Treatment: Orotic aciduria
Oral uridine administration
Substituting purine for pyrimidine or vice versa
Substituting purine for purine or pyrimidine for pyrimidine
inhibits lipoic acid, causes vomiting, rice water stools, garlic breath
Rate-determining enzymes of metabolic processes - Urea cycle
Carbamoyl phosphate synthetase I
Rate-determining enzymes of metabolic processes - TCA cycle
Rate-determining enzymes of metabolic processes - Ketogenesis
Rate-determining enzymes of metabolic processes - HMP shunt
Glucose-6-phosphate dehydrogenase (G6PD)
Rate-determining enzymes of metabolic processes - Glycolysis
Rate-determining enzymes of metabolic processes - Glycogenolysis
Rate-determining enzymes of metabolic processes - Glycogen synthesis
Rate-determining enzymes of metabolic processes - Gluconeogenesis
Rate-determining enzymes of metabolic processes - Fatty acid synthesis
Acetyl-CoA carboxylase (ACC)
Rate-determining enzymes of metabolic processes - Fatty acid oxidation
Carnithine acyltransferase I
Rate-determining enzymes of metabolic processes - De novo pyrimidine synthesis
Carbamoyl phosphate synthetase II
Rate-determining enzymes of metabolic processes - De novo purine synthesis
Rate-determining enzymes of metabolic processes - Cholesterol synthesis
Pyruvate dehydrogenase complex
The complex contains 3 enzymes that require 5 cofactors: 1. Pyrophosphate (B1); 2. FAD (B2); 3. NAD (B3); 4. CoA (B5); 5. Lipoic acid Activated by exercise: ↑NAD+/NADH ratio, ↑ADP, ↑Ca2+
Pyrimidines are made from?
Orotate precursor, with PRPP added later
Purines are made from?
Deletion of normally active Paternal allele Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
Ornithine transcarbamoylase deficiency
(↓urea cycle), leads to an accumulation of carbamoyl phosphate, which is then converted to orotic acid
Octamer subunit amino acids
Lysine and Arginine
Nucleotide that has a methyl
Nucleotide that has a ketone
mRNA start codons code for?
Eukaryotes: Methionine Prokaryotes: Formyl-methionine (f-Met)
Molecular motor proteins: Kinesin
anterograde to microtubule
Molecular motor proteins: Dynein
retrograde to microtubule
Modes of inheritance - Mitochondrial myopathies
Modes of inheritance - Leber's hereditary optic neuropathy
Mitochondrial inheritance, degeneration of retinal ganglion cells and axons. Leads to acute loss of central vision.
Modes of inheritance - Hypophosphatemic rickets
formerly known as vitamin D resistant rickets. Inherited X-linked dominant disorder resulting in ↑ phosphate wasting at proximal tubule. Results in rickets-like presentation.
inhibits bacterial dihydrofolate reductase (↓dTMP)
bind 30S subunit, preventing attachment of aminoacyl-tRNA
inhibits by binding to K+ site
MOA: Orotic aciduria
Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to defect in either orotic acid phosphoribosyltransferase or ototidine 5'-phosphate decarboxylase. Autosomal recessive.
MOA: Methotrexate (MTX)
inhibits dihydrofolate reductase (↓dTMP)
bind 50S, blocking translocation
inhibits ribonucleotide reductase
binds 50S, blocking translocation
inhibits 50S peptidyltransferase
MOA: Cardiac glycosides (digoxin and digitoxin)
directly inhibit the Na+-K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange. ↑ [Ca2+]i → ↑ cardiac contractility.
inhibit formation of the initiation complex and cause misreading of mRNA
MOA: 6-mercaptopurine (6-MP)
blocks de novo purine synthesis
MOA: 5-fluorouracil (5-FU)
inhibits thymidylate synthase (↓dTMP)
Metabolism sites - Mitochondria (4)
Fatty acid oxidation (β-oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation
Metabolism sites - Cytoplasm (5)
Glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
Metabolism sites - Both (3)
Heme synthesis, Urea cycle, Gluconeogenesis (HUGs takes two)
caused by a defect in fibrillin
energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat, and variable edema.
Major apolipoproteins - E
Mediates extra (remnant) uptake
Major apolipoproteins - C-II
Cofactor for lipoprotein lipase
Major apolipoproteins - B-48
Mediates chylomicron secretion
Major apolipoproteins - B-100
Binds to LDL receptor, mediates VLDL secretion
Major apolipoproteins - A-I
Lysosomal storage diseases - Tay-Sachs disease
Findings: Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly (vs. Niemann-Pick) Deficient enzyme: Hexosaminidase A Accumulated substrate: GM2 ganglioside Inheritance: AR
Lysosomal storage diseases - Niemann-Pick disease
Findings: Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells Deficient enzyme: Sphingomyelinase Accumulated substrate: Sphingomyelin Inheritance: AR
Lysosomal storage diseases - Metachromatic leukodystrophy
Findings: Central and peripheral demyelination with ataxia, dementia Deficient enzyme: Arylsulfatase A Accumulated substrate: Cerebroside sulfate Inheritance: AR
Lysosomal storage diseases - Krabbe's disease
Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells Deficient enzyme: Galactocerebrosidase Accumulated substrate: Galactocerebroside Inheritance: AR
Lysosomal storage diseases - Hurler's syndrome
Findings: Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly Deficient enzyme: α-L-iduronidase Accumulated substrate: Heparan sulfate, dermatan sulfate Inheritance: AR
Lysosomal storage diseases - Hunter's syndrome
Findings: Mild Hurler's + aggressive behavior, no corneal clouding Deficient enzyme: Iduronate sulfatase Accumulated substrate: Heparan sulfate, dermatan sulfate Inheritance: XR
Lysosomal storage diseases - Gaucher's disease (most common)
Findings: Hepatosplenomegaly, aseptic necrosis of the femur, bone crisis, Gaucher's cells (macrophages that look like crumpled tissue paper) Deficient enzyme: β-glucocerebrosidase Accumulated substrate: Glucocerebroside Inheritance: AR
Lysosomal storage diseases - Fabry's disease
Findings: Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease Deficient enzyme: α-galactosidase A Accumulated substrate: Ceramide trihexoside Inheritance: XR
Liver enzyme - Pancreatic lipase
degradation of dietary TG in small intestine
Liver enzyme - Lipoprotein lipase (LPL)
degradation of TG circulating in chylomicrons and VLDLs
Liver enzyme - Hormone-sensitive lipase
degradation of TG stored in adipocytes
Liver enzyme - Hepatic TG lipase (HL)
degradation of TG remaining in IDL
X-linked recessive, defective purine salvage owing to absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production. Findings: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
protein malnutrition resulting in skin lesions, edema, liver function (fatty change due to ↓ apolipoprotein synthesis). Clinical picture is a small child with swollen belly. Malnutrition, Edema, Anemia, fatty Liver.
immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out); associated with situs inversus
At a single locus, only 1 allele is active; the other is inactive (imprinted / inactivated by methylation). Deletion of the active allele → disease Both syndromes due to inactivation or deletion of genes on chromosome 15 Can also occur as a result of uniparental disomy
Immunohistochemical stains: Vimentin
Immunohistochemical stains: Neurofilaments
Immunohistochemical stains: GFAP
Immunohistochemical stains: Desmin
Immunohistochemical stains: Cytokeratin
(inclusion cell disease) - inherited lysosomal storage disorder; failure of addition of mannose-6-phosphate to lysosome proteins (enzymes are secreted outside the cell instead of being targeted to the lysosome). Results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Often fatal in childhood.
Condensed, transcriptionally inactive, sterically inaccessible
Hardy-Weinberg law assumptions (4)
1. No mutation occuring at the locus 2. No selection for any of the genotypes at the locus 3. Completely random mating 4. No migration
Glycogen storage diseases - Von Gierke's disease (type I)
Findings: severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood lactate, hepatomegaly Deficient enzyme: Glucose-6-phosphatase
Glycogen storage diseases - Pompe's disease (Type II)
Findings: Cardiomegaly and systemic findings leading to early death Deficient enzyme: Lysosomal α-1,4-glucosidase (acid maltase)
Glycogen storage diseases - McArdle's disease (type V)
Findings: ↑ glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria with stenuous exercise Deficient enzyme: Skeletal muscle glycogen phosphorylase
Glycogen storage diseases - Cori's disease (type III)
Findings: milder form of type I with normal blood lactate levels Deficient enzyme: Debranching enzyme (α-1,6-glucosidase)
Genetic terms: Variable expression
Nature and severity of phenotype vary from 1 individual to another
Genetic terms: Uniparental disomy
Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent
Genetic terms: Pleiotropy
1 gene has > 1 effect on an individual's phenotype
Genetic terms: Mosaicism
Occurs when cells in the body have different genetic makeup. Can be a germ-line mosaic, which may produce disease that is not carried by parent's somatic cells
Genetic terms: Loss of heterozygosity
If a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. This is not true of oncogenes.
Genetic terms: Locus heterogeneity
Mutations at different loci can produce the same phenotype
Genetic terms: 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.
Genetic terms: Incomplete penetrance
Not all individuals with a mutant genotype show the mutant phenotype
Genetic terms: Imprinting
Differences in phenotype depend on whether the mutation is of maternal or paternal origin
Genetic terms: Heteroplasmy
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondial inherited disease.
Genetic terms: Dominant negative mutation
Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning.
Genetic terms: Codominance
Neither of 2 alleles is dominant
Genetic terms: Anticipation
Severity of disease worsens or age of onset of disease is earlier in succeeding generations
Genetic code features: Universal
Genetic code is conserved throughout evolution
Genetic code features: Unambiguous
Each codon specifies only 1 amino acid
Genetic code features: Degenerate / redundant
More than 1 codon may code for the same amino acid
Genetic code features: Commaless, nonoverlapping
Read from a fixed starting point as a continuous sequence of bases
Findings: Orotic aciduria
↑ orotic acid in urine, megaloblastic anemia (does not improve with administration of vitamin B12 or folic acid), failure to thrive. No hyperammonemia (vs. OTC deficiency - ↑ orotic acid with hyperammonemia)
Less condensed, transcriptionally active, sterically accessible
Ethanol metabolism: Fomepizole
inhibits alcohol dehydrogenase and is an antidote for methanol of ethylene glycol poisoning
Ethanol metabolism: Disulfiram (Antabuse)
inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms)
can be caused by α1-antitrypsin deficiency, resulting in excess elastase activity
Stretchy protein within lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae → relaxed and stretched conformations). √. Rich in proline and glycine, nonglycosylated forms. √. Tropoelastin with fibrillin scaffolding. √. Broken down by elastase, which is normally inhibited by α1-antitrypsin.
Drugs that act on microtubules
1. Mebendazole / thiabendazole (antihelminthic) 2. Griseofulvin (antifungal) 3. Vincristine / vinblastine (anti-cancer) 4. Paclitaxel (anti-breast cancer) 5. Colchicine (anti-gout)
DNA replication: Single-stranded binding proteins
Prevent strands from reannealing
DNA replication: Replication disk
Y-shaped region alond DNA template where leading and lagging strands are synthesized
DNA replication: Proofreads
DNA polymerase III has 5' → 3' synthesis and proofreads with 3' → 5' exonuclease DNA polymerase I excises RNA primer with 5' → 3' exonuclease
DNA replication: Primase
Makes an RNA primer on which DNA polymerase III can initiate replication
DNA replication: Origin of replication
Particular sequence in genome where DNA replication begins. May be single (prokaryotes) or multiple (eukaryotes)
DNA replication: Helicase
Unwinds DNA template at replication fork
DNA replication: DNA topoisomerases
Create a nick in the helix to relieve supercoils created during replication
DNA replication: DNA polymerase III
Prokaryotic only. Elongates leading strand by adding deoxynucleotides to the 3' end. Elongates lagging strand until it reaches primer of preceeding fragment. 3' → 5' exonuclease activity "proofreads" each added nucleotide
DNA replication: DNA polymerase I
Prokaryotic only. Degrades RNA primer and fills in the gap with DNA
DNA replication: DNA ligase
DNA repair: Nucleotide excision repair
Specific endonucleases release the oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively. Mutated in xeroderma pigmentosum
DNA repair: Nonhomologous end joining
Brings together 2 ends of DNA fragments. No requirement for homology
DNA repair: Mismatch repair
Unmethylated, newly synthesized string is recognized, mismatched nucleotides are removed, and the gap is filled and resealed. Mutated in Hereditary nonpolyposis colorectal cancer (HNPCC)
DNA repair: Base excision repair
Specific glycosylases recognize and remove damaged bases, AP endonuclease cuts DNA at apyrimidinic site, empty sugar is removed, and the gap is filled and resealed.
Cytoskeletal elements: Microtubule (5)
Cilia, flagella, mitotic spindle, neurons, centrioles
Cytoskeletal elements: Intermediate filaments (5)
Vimentin, desmin, cytokeratin, glial fibrillary acid proteins (GFAP), neurofilaments
Cytoskeletal elements: Actin and myosin (4)
Microvilli, muscle contraction, cytokinesis, adherens junctions
microtubule polymerization defect resulting in ↓ phagocytosis. Results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy
Carbamoyl phosphate is involved in which 2 metabolic pathways?
1. de novo pyrimidine synthesis 2. urea cycle
Autosomal dominant diseases - von Hippel-Lindau disease
Findings: hemangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors. Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p). Results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors. Von Hippel-Lindau = 3 words for chromosome 3.
Autosomal dominant diseases - Tuberous sclerosis
Findings: facial lesions (adenoma sebaceum), hyperpigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, ↑ incidence of astrocytomas. Incomplete penetrance, variable presentation.
Autosomal dominant diseases - Neurofibromatosis type 2
Bilateral acoustic schwannomas, juvenile cataracts. NF2 gene on chromosome 22; type 2 = 22.
Autosomal dominant diseases - Neurofibromatosis type 1 (von Recklinghausen's disease)
Findings: café-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal disorders (e.g., scoliosis) and optic pathway gliomas. On long arm of chromosome 17; 17 letters in von Recklinghausen.
Autosomal dominant diseases - Marfan's syndrome
Fibrillin gene mutation → connective tissue disorder affecting skeleton, heart, and eyes. Findings: tall with long extremities, pectus excavatum, hyperextensive joints, and long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta → aortic incompetence and dissecting aortic aneurysms; floopy mitral valve. Subluxation of lenses.
Autosomal dominant diseases - Huntington's disease
Findings: depression, progressive dementia, choreiform movements, caudate atrophy, and ↓ levels of GABA and ACh in the brain. Symptoms manifest in affected individuals between the ages 20 and 50. Gene located on chromosome 4; trinucleotide repeat disorder: (CAG)n. "Hunting 4 food"
Autosomal dominant diseases - Hereditary spherocytosis
Spheroid erythrocytes due to spectrin or ankyrin defect; hemolytic anemia; ↑ MCHC. Splenectomy is curative.
Autosomal dominant diseases - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
Inherited disorder of blood vessels. Findings: telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs).
Autosomal dominant diseases - Familial hypercholesterolemia (hyperlipidemia type IIA)
Elevated LDL due to defective or absent LDL receptor. Heterozygotes (1:500) have cholesterol ≈ 300mg/dL. Homozygotes (very rare) have cholesterol ≈ 700+mg/dL, severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon); MI may develop before age 20.
Autosomal dominant diseases - Familial adenomatous polyposis
Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected. Mutation on chromosome 5 (APC gene); 5 letters in "polyp".
Autosomal dominant diseases - Autosomal-dominant polycystic kidney disease (ADPKD)
Formerly known as adult polycystic kidney disease. Always bilateral, massive enlargement of kidneys due to multiple large cysts. Patients present with flank pain, hematuria, hypertension, progressive renal failure. 90% of cases are due to mutation in APKD1 (chromosome 16; 16 letters in "polycystic kidney"). Associated with polycystic liver disease, berry aneurysms, mitral valve prolapse. Infantile form is recessive.
Autosomal dominant diseases - Achondroplasia
Cell-signaling defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism; short limbs, but head and trunk are normal size. Associated with advanced paternal age.
Deletion of normally active maternal allele Mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet")
Amino acids necessary for purine synthesis
Glycine, Aspartate, Glutamine