Example of dominant versus recessive genetics
Eye color, pea smoothness, pea color
Marfan Syndrome is an example of what type of genetic insufficiency?
Haploinsufficiency syndrome, 50% of a gene product results in mutant disorder
What type of 'Loss of Function Mutation' is Osteogenesis Imperfecta?
Dominant Negative, mutation in a gene whose products are a component of a protein complex
What type of 'Loss of Function Mutation' is Huntington's Disease?
Dominant Negative, mutation in gene causes the gene product to bind or inhibit another protein's activity
What type of 'Loss of Function Mutation' is Early Prostate Cancer?
Dominant Negative, mutant causes hyperactivity of gene product
What are the two main mechanisms for nucleoside/nucleotide analog pharmaceuticals?
Inhibition of nucleic acid sythesis, DNA incorporation leading to termination
Azidothymidine (AZT) (desc)
Nucleoside analog which lacks a free 3' OH, high affinity for reverse transcriptase, used against HIV
Didanosine (ddl) (desc)
Nucleoside analog which lacks a free 3' OH, high affinity for reverse transcriptase, used against HIV
Nucelotide analog which possesses open chain structure in place of pentose, inhibitor of viral DNA polymerase, causes termination of DNA replication, used against Herpes
Nucelotide analog which possesses open chain structure in place of pentose, inhibitor of reverse transcriptase, used against HIV
e.g. Cytosine a. and Adenosine a., planar structures which inhibit DNA polymerase, induce DNA damage via DNA incorporation, anti-cancer drugs
Cytidine Analogs (desc)
e.g. 5-aza-2'-deoxycytidine and 5-azacytidine, disrupt epigenetic process of DNA methylation (via N atom at position 5 of cytidine), inhibitors of DNA-methyl-transferase
Converted to FdUMP which inhibits thymidylate kinase > inhibits thymine synthesis, anti-cancer drugs
Metabolized to 6-mercaptopurine, surpresses organ rejection
Inhibits xanthine oxidase allowing less products to be converted to uric acid, gout treatment
Adenosine (Adenocard) (desc)
Used to treat supraventricular tachycardia, also used to treat sleep regulation
Is converted to acyclovir triphosphate by thymidine kinase, which serves as substrate for viral DNA pol, lack of 3' -OH causes DNA termination
Cytarabine (Other Name)
Vidarabine (Other Name)
Inhibits DNA gyrase, leaving DNA supercoiled (quinalone drug)
RNA Dependent RNA Polymerase (Replicase) (desc)
Transcribe RNA from RNA template
Examples of RNA Dependent RNA Polymerases (Replicases)
Polio, Hepatitis C, Dengue Fever, Rubella, West Nile, Common Cold
RNA Dependent DNA Polymerase (desc)
Single stranded RNA genome, transcribes DNA from RNA template using reverse transcriptase, DNA copy inserted into host genome
Example of RNA Dependent DNA Polymerase
Death Cap Mushroom (amanita phalloides, mech)
Produces alpha-amanitin which inhibits RNA pol II
Phases of Death Cap Mushroom poisoning
1) Asymptomatic, 2) Severe diarrhea/vomiting, 3) Apparent recovery, 4) Renal/Liver failure > death (7-10 days)
Antibiotic which inhibits bacterial gyrase
Family of antibiotics that inhibit bacterial gyrases, e.g. novobiocin
Family of antibiotics that inhibit bacterial gyrases, e.g. nalidixic acid, ciproflaxin
Rifamycin (Rifampen) (mech)
Antibiotic that inhibits transcription initiation in prokaryotes
Actinomycin D (mech)
Inhibits transcription and replication in both prokaryotes and eukaryotes by interchelating dsDNA, not allowing it to unwind
Example of eicosanoid, inhibition of prostaglandin and thromboxane synthesis, e.g. Aspirin
Releases NO, used to treat angina pectoris
Which adrenergic receptor would be targeted by bronchodilators?
Beta-2 (Gs > increased cAMP > smooth muscle relaxation)
Cholera Toxin (mech)
ADP ribosylates alpha subunit of Gs rendering GTP unable to hydrolyze to GDP, chloride channel permanently open > cell dehydration
T/F: Mutations in RAS genes can lead to cancer
Approximately what percentage of human cancers are known to have mutations in RAS genes?
T/F: Proto-oncogenes are mutated
T/F: Oncogenes are mutated
Symptoms of lineoleic acid deficiency
Scaly dermatitis, hair loss, poor wound healing
Linoleic acid deficiency (test)
Mead acid (formed from oleic acid, signals linoleic acid deficiency)
Total Parenternal Nutrition (TPN) (def)
Intravenous essential FA administration
Respiratory Distress Syndrome (def, etiologies)
Deficiency of lung surfactant either by premature birth, type II pneumocyte harm or ABC transporter (delivers surfactant) defect
What is indicated from the ratio of PC to sphingomyelin?
Fetal lung maturity
What ratio of PC (Lecithin):sphingomyelin is indicative of fetal lung maturity?
Caveolae (def, pathology mech)
Patches of plasma membrane with unique protein/lipid composition, pathogens usually enter cells here
T/F: Diabetic patients can utilize GLUT 4 transporters
Describe the relationship between SGLT 2 and diabetic patients
SGLT 2 may help in the uptake of glucose by nephrons in diabetic patients
Cystic Fibrosis Transmembrane Regulator (CFTR) (desc)
An ABC-transporter, once two ATPs are cleaved, the channel opens allowing chloride ions to pass out of the cell
Name a non-CFTR clinical function of ABC-transporters
Drug excretion (multidrug resistance, cancer), Surfactant release into alveoli, Free cholesterol release to HDL transport to liver
Physiological results of cystic fibrosis
Thick mucus in respiratory and intestinal mucosal linings, congenital bilateral absence of vas deferens
Codon 508: Phenylalanine
Most common mutation site for CFTR gene
Cystic Fibrosis (diagnostic)
Sweat test, high NaCl concentrations outside of the cell
Deficiency of CAT1 or CAT2 enzymes result in the loss of what energy producing pathway?
Jamaican vomiting sickness is caused by eating what?
Unripe fruit of the ackee tree
Unripe ackee fruit contains hypoglycin. Hypoglycin produces what effect?
Powerful irreversible inhibitor of medium and short chain acyl-CoA dehydrogenases > inhibition of beta oxidation
What congenital defect results in soluble acyl carnitines being found in the blood and urine?
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
What deficiency can result in methylmalonate production being found in the urine and bloodstream of affected patients?
Vitamin B12 (pernicious anemia, methylmalonyl-CoA mutase malfunction)
What general defect is caused by the biogenetic lack of peroxisomes in all tissues?
What is the name of the rare autosomal recessive genetic disorder in which alpha-oxidation is impaired?
What molecules are found in the blood stream during period of starvation and/or uncontrolled type one diabetes?
During metabolic analysis, which ketone bodies can help determine the reduction status of a patient's mitochondria?
Acetoacetate and 3-hydroxybutyrate
An increased concentration of ketone bodies in the blood is termed what?
An increased concentration of ketone bodies in the urine is termed what?
A hydrogen ion imbalance associated with the production of ketone bodies is termed what?
Acetylsalicylic acid is what type of enzymatic inhibitor?
What molecule acts as a structural analogue of succinate, which drives its function as a competitive inhibitor of succinate dehydrogenase?
What molecule binds to the Fe2+ ion in the active site of aconitase, rendering the reaction inhibited?
What is the mechanism of phenylketouria?
Deficiency in phenylalanine hydroxylase, diversion of metabolism to phenyl ketone derivatives
What molecule (relating to Maple Syrup Disease) accumulates in children causing the inhibition of mitochondrial pyruvate translocase?
Describe maple syrup urine disease
A genetic disorder causing a defect in branched-chain amino acid metabolism
Name two molecules that react with lipoamide and prevent it from reacting within the PDH complex
T/F: Agent 2,3-dimercaptopropanol removes the inhibition of PDH caused by Hg2+ and/or arsenite
A deficiency of what cofactor results in Beri-beri disease?
T/F: Westerners are most prone to Beri-beri disease than Asians
T/F: Thiamine can be obtained from the diet in rice, meat and yeast
What condition results when a minor deficiency of thiamine is present?
Dry beri-beri disease
What condition results when a major deficiency of thiamine is present?
Wet beri-beri disease
What condition results when thiamine deficiency is combined with alcohol abuse?
T/F: Severe defects in any PDH enzymes can lead to neurological disease which can result in mental retardation or death
What condition(s) results from the build up of lactate due to PDH deficiency?
Leigh's disease (acidosis from increased amounts of lactate)
Where is the gene found which encodes for the alpha subunit of the E1 part of the PDH complex (common deficiency)?
While no cure is presently available for PDH diseases, what type of diet benefits some patients?
Low carbohydrate, high fat
Proteins that are misfolded are generally tagged as defective with ubiquitin. In what neural disease(s) is this function not present?
Alzheimer's disease, prion disease
T/F: DHP (di-isopropyl phosphofluoridate) is an irreversible inhibitor is acetylcholine esterase
To which residue does DHP bind to tin render acetylcholine esterase inhibited?
Serine in catalytic site
T/F: Aspirin is a reversible inhibiter
What enzyme does aspirin irreversibly inhibit?
What is the amino acid related mechanism of aspirin inhibition?
Aspirin acetylates a serine residue in the active site of cyclooxygenase
Is Lovastatin a competitive or non-competitive inhibitor based on the information that it binds to the enzyme's active site?
T/F: Myocardial cells must die in order for their contents to be released
T/F: Hepatocytes must die in order for their contents to be released
What is the half-life of creatine kinase in the blood?
What is the half-life of aspartate aminotransferase in the blood?
1day (cytosol), 1hr (mitochondria)
What is the half-life of lactate dehydrogenase (LDH1) in the blood?
T/F: Creatine kinase is found in the liver
What pathologies can CK markers be used for?
AMI, rhabdomyolosis, muscular dystrophy, acute renal failure
What are the subunits of creatine kinase?
M and B
Where is CK-BB found?
Brain, intestinal smooth muscle
T/F: CK-BB accumulates in serum
In myocardium, what percentage of CK is CK-MB?
In myocardium, what percentage of CK is CK-MM?
Generally, what percentage of total CK needs to be CK-MB to be indicative of an MI?
Where is CK-MM primarily found?
Approximately what percent of skeletal muscle CK is CK-MB?
How can CK isozymes be separated?
What serum markers can be visualized within hours of an acute MI?
CK-MB, troponin I, troponin T, myoglobin
T/F: Myoglobin is specific to the heart
T/F: Tropnin C does not have an isozyme that is specific for the heart
What are the two subunits of the serum marker LDH?
H and M
In what body area(s) can LDH1 normally be found?
Heart > RBC
In what body area(s) can LDH2 normally be found?
RBC > Heart
In what body area(s) can LDH5 normally be found?
Liver > Muscle
T/F: Normally, the body has a low LDH1/LDH2 ratio
T/F: Upon cardiac injury, the switch to a high LDH1/LDH2 ratio is termed the 'LDH Flip' and is indicative of an MI
Approximately how long does CK-MB take to again reach baseline once increased?
T/F: Functional liver failure does not occur until 80% of the liver capacity has been damaged
Which enzyme is found more in hepatocytes than any other tissue in the body and can be indicative of liver damage via systemic cirulation?
Alanine aminotransferase (ALT, sALT)
Which enzyme is found in hepatocyte cytosol and mitochondria and can be indicative of liver damage via systemic circulation?
Aspartate aminotransferase (AST, sAST)
T/F: An indicator for ethanol-related liver damage would be a sAST/sALT <2
This enzyme can be found in liver, bone, intestine and placenta. Its placement in the blood can be indicative of cirrhosis or gall stones.
Alkaline phosphatase (ALP)
This enzyme is involved in the gamma-glutamyl cycle and can be induced in the liver after high ethanol intake or due to medical drugs.
Which serum marker(s) might be elevated during biliary tree obstruction?
What is a common serum marker for prostate cancer?
What is a common serum marker for liver cancer?
What are common serum markers for acute pancreatitis?
Alpha-amylase, pancreatic lipase
What occurs when there are variations in the DNA sequence of the cytochrome p450 gene?
Variations in the individual's ability to metabolize certain drugs
What is the mechanism behind osteogenesis imperfecta?
Abnormal collagen formation leading to brittle bones
Nalidixic acid (mech)
Inhibits DNA gyrase, leaving DNA supercoiled (quinalone drug)
Individuals with lupus possess antibodies that attack which component of a splicesome?
U1 RNA component
T/F: Individuals with beta-thalasemmia have mutations in the beta globin gene that generate additional splice sites within the mRNA
A mutation in the calpain 3 gene that generates a new splice site within exon 16 occurs in which disease?
Limb Girdle Muscular Dystrophy
This disease can be common in most adults and leads to bloating and diarrhea after ingestion of milk
What is the main mechanism for Kwashiorkor manifestations?
Insufficient dietary protein (primarily albumin)
T/F: Antacids do not interfere with protein degredation
Deficiency of conjugated bile salts can lead to which two conditions
Gallstones and/or steatorrhea
T/F: Steatorrhea can lead to lack of dietary fatty acids and fat-soluble vitamins
A lack of which fat-soluble vitamin may lead to night blindness
What is the condition termed that results from activation of digestive enzymes while still in the pancreas?
Patients suffering from cystic fibrosis should eat what type of diet?
Frequently eat diet rich in milk and TAGs with medium chain FAs
List some common causes for cholelithiasis
Decreased amounts of bile salts (PC in bile), increased biliary cholesterol secretion
What is primary lactose intolerance?
Reduced lactase activity, common with age
What is secondary lactose intolerance?
Intestinal injury stemming from severe diarrhea, gastroenteritis (rotavirus) or celiac disease
In which populations is primary lactose intolerance most prevalent?
Asians, African-Americans, Native Americans
In which population is primary lactose intolerance lease prevalent?
Northern Europe societies
What is congenital lactase deficiency?
A rare autosomal recessive disorder (previously life-threatening)
The sugar-type ring in arabinose drugs is termed what?
What molecule may accumulate in the eye, potentially leading to cataracts or blindness?
What population is particularly prone to MCADD deficiency?
Nursing infants (as they are reliant on FA nutrition)
This molecule is an important diagnostic indicator of high plasma ketone body levels when detected on the breath of affected individuals
The PKU disorder can result in an accumulation of phenylpyruvate, which inhibits what molecule transporter?
T/F: Thiamine is required to make the prosthetic group of alpha-ketoglutarate dehydrogenase and transketolase
List some inhibitors of Complex I within the ETC
Rotenone, Amytal, Piericidin A
Name an inhibitor of Complex III within the ETC
List some inhibitors of Complex IV within the ETC
Cyanide, Azide, H2S, Carbon monoxide
T/F: Rotenone is used as a fish poison by South American Indians
T/F: Amytal is a barbituate
T/F: Cyanide, azide and H2S all bind to the Fe3+ form of cytochrome a3
T/F: Carbon monoxide binds to the Fe3+ form of cytochrome a3
Synthesis of ATP can be inhibited by this drug, which binds to one of the subunits of Fo and prevents re-entry of H+ ions into the mitochondrial matrix
This molecule acts as an uncoupler of the ETC by providing a means whereby H+ ions can re-enter into the mitochondrial matrix without participating in ATP synthase
This substance destroys that inner mitochondrial membrane potential by bringing K+ ions within the membrane
This substance uncouples the ETC by forming a hydrophilic trans-membrane channel, through which ions can cross the membrane
This substance forms channels in the inner mitochondrial membrane which allows ions such as Cl- and OH- to pass from the matrix to the intermembrane space, resulting in heat release
T/F: Thermogenin occurs naturally to aid in newborn infant heat maintenance
This compound is a competitive inhibitor of the ATP/ADP translocase transport protein
This compound is another inhibitor (non-Atractyloside) of ATP/ADP translocase transport
T/F: Atrctyloside, bongkrekik acid and oligomycin all may eventually lead to ETC shutdown by the presence of such a large H+ gradient
Are mitochondrial diseases transmitted maternally or paternally?
T/F: Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disease
T/F: Myoclonic Epilepsy and Ragged-Red-Fiber Disease (MERRF) is a mitochondrial-based disease
T/F: Mitochondrial Myopathy, Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) is a mitochondrial-based disease
T/F: Aminoglycoside Induced Deafness is a mitchondrial-based disease
T/F: Glycogen storage diseases are numbered (e.g. I, II)
Which of the glycogen storage diseases is most common?
Von Gierke's (Type I)
Which enzyme is faulty in von Gierke's disease?
Which glycogen storage disease results from the deficiency of lysosomal alpha-1,4 and 1,6 glucosidase enzymes?
Which glycogen storage disease results from the absence of debranching enzyme?
Cori's (Type III)
Which glycogen storage disease results from the absence of branching enzyme?
Andersen's (Type IV)
T/F: Anderson's disease is fairly common
Which glycogen storage disease results from the absence of muscle phosphorylase?
McArdle's (Type V)
Which glycogen storage disease results from a deficiency in liver phosphorylase?
Hers' (Type VI)
Which glycogen storage disease results from a deficiency of PFK1 in muscle and RBCs?
Tarui's (Type VII)
Which of the glycogen storage diseases are most fatal?
Pompe's (II), Andersen's (IV)
What is a mneumonic for glycogen storage diseases (1-6)?
Viagra Pills Cause A Major Hardon
What is a mneumonic for glycogen storage diseases (1-7)?
Go Pick Cherries And Make Her Talk
What condition may arise when drugs such as primaquine, aspirin, sulfonamides are administered? (possibly with the addition of fava beans)
Drug Induced Hemolytic Anemia
What condition results from a deficiency in glucose-6-phosphate dehydrogenase?
Drug Induced Hemolytic Anemia
T/F: Drug Induced Hemolytic Anemia is not a sex linked genetic disorder
What ethnic groups suffer most from Drug Induced Hemolytic Anemia?
African, Mediterranean, Black Americans
What condition is caused by a defect in the gene for aldolase B?
Hereditary Fructose Intolerance (HFI)
T/F: Hereditary Fructose Intolerance (HFI) is inherited in an autosomal dominant manner
What condition results from a defect in the fructokinase enzyme?
What enzyme deficiency/deficiencies causes galactosemia and/or galactosuria?
Galactokinase, Galactose 1-Phosphate Uridyl Transferase
What is a clinical result of the accumulation of galactitol?
What enzyme is deficient in classical galactosemia?
Galactose 1-Phosphate Uridyl Transferase
How can both galactokinase and galactose 1-phosphate uridyl transferase deficiencies by treated via the diet?
Restricting the intake of galactose
Which set of diseases affect the proper development/maintenance of the skeletal system and are characterized by a defect in sulfation in growing GAG chains?
What is the name of the bacteria primarily responsible with causing gastric ulcerations?
A dysfunctional ECM may result in which pathologies?
Cancer cell mobility, osteoarthritis, rheumatoid arthritis, renal malfunction
Vitamin C deficiency can lead to improper collagen formation, known to clinicians as what pathology?
What disease may result from defect enzymes in collagen synthesis?
Which type of Osteogenesis Imperfecta is the mildest?
Which type of Osteogenesis Imperfecta is the most severe?
Which type of Osteogenesis Imperfecta is the most common?
What protein is defective in Marfan's Syndrome?
T/F: Pompe's disease is classified as both a glycogen storage and lysosomal storage disease
A deficiency in iduronate sulfatase leads to this LSD
Hunter Syndrome (MPS II)
List some characteristics/symptoms of individuals with Hunter Syndrome
Broad range of severity, facial feature coarseness, frequent ear/respiratory infection, mental retardation, deafness, short stature, claw hands, hepatosplenomegaly
A deficiency in iduronase leads to this LSD
Hurler Syndrome (MPS I)
List some characteristics/symptoms of individuals with Hurler Syndrome
Short stature, choarse facial features, macrocephaly, restricted joint mobility, hepatosplenomegaly, cloudy corneas, moderately severe mental delay
Which LSD is more severe, Hunter or Hurler?
What is the common diagnostic for either Hunter or Hurler Syndrome?
GAGs in urine
Which LSD, Hunter or Hurler, is X-linked?
Which LSD, Hunter or Hurler, presents with the symptom of corneal clouding?
List different sphingolipidoses
Tay-Sach's, Fabry, Gaucher's, Niemann-Pick Diseases
Which enzyme is deficient in Tay-Sach's disease?
Beta hexosaminidase A
Which metabolic storage diseases present with cherry-red macula inclusions?
Tay-Sach's, Hurler Syndrome, Niemann-Pick Disease
T/F: Tay-Sach's can present in either an infantile or late-onset form
Which LSD presents with reddish skin lesions, impaired sweating, burning/tingling of extremities, and/or muscle weakness/fatigue?
T/F: Fabry's Disease is not X-linked
T/F: The Fabry's Disease symptom of reddish skin lesions are usually hidden under clothes
Which LSD is the most prevalent?
Histologically, what appearance does Gaucher's Disease give?
Crumpled tissue paper within the cytoplasm
T/F: Gaucher's Disease is often found in infants
List two symptoms of Gaucher's Disease in adults
Severe hepatosplenomegaly, osteoporosis of long bones
Name the disorder that results from a defect in transport of several lysosomal enzymes from their synthesis in the ER into lysosomes
T/F: I-Cell Disease is considered rare
Which LSD is similar to Hurler Syndrome but has an earlier onset and presents with no GAGs in the urine?
The deficiency of acid sphingomyelinase results in which LSD?
What compound accumulates in the spleen, liver and brain in Niemann-Pick Disease?
T/F: Type A Niemann-Pick Disease is considered classic infantile and does not lead to death
T/F: Type B Niemann-Pick Disease is considered visceral and does not lead to death
Which compound accumulates in Tay-Sach's Disease?
Which enzyme is deficient in Fabry's Disease?
Alpha galactosidase A
Which compound accumulates in Fabry's Disease?
Which enzyme is deficient in Gaucher's Disease?
Which compound acumulates in Gaucher's Disease?
I-Cell Disease results from an absence of what?
What other alias does I-Cell Disease have?
Which enzyme is deficient in Niemann-Pick Disease?
What is the purpose of alpha-antitrypsin?
Inhibit neutrophil elastase
Where is alpha-antitrypsin mostly synthesized?
This agent is an irreversible inhibitor of acetylcholine esterase as it covalently binds to the serine in the active site
Di-isopropyl phosphofluoridate (DFP)