week 2 Flashcards
Thalassemia
autosomal recessive; caused by many types of genetic mutations that lead to common outcome- reduced or elimination of globin proteins, leading to loss of oxygen carrying capacity and aggregation of remaining globin chains, causing RBC destruction; major type called Cooley’s Anemia is complete absence of beta globin- serious side effects; minor form is reduced amounts of beta globin, no symptoms unless high altitude or exertions; disease can be caused by mutation in splice junctions; mutation in invariant sequence results in NO splicing- major form, may result in use of cryptic splice junction in middle of intron- non-functional protein; mutation in consensus sequence leads to reduced splicing, milder outcome
Shiga toxin
found in certain E coli strains; contains RNA glycosidase activity and eliminates a critical A residue from the catalytic 28S rRNA in the large ribosomal unit, meaning that peptide bond formation can no longer occur-inhibits translation, causing human cell death
Cholera and diptheria
target the eEF2 elongation factor, important for translocation of the ribosome, resulting in dead human cells
sonic hedgehog disease
autosomal dominant preaxial polydactyly; single base change in an enhancer region drastically affects Tc of sonic hedgehog gene
Sulfonylurea-based drugs (glipizide)
given to type II diabetics; they bind to and close the potassium channels on the beta cells in order to increase calcium influx and thus insulin release from the beta cells
MODY: Maturity onset diabetes of the young
usually age 15-25; genetic mutation, may be in glucokinase which decreases its affinity for glucose (higher Km), leading to a higher threshold of glucose needed in order to enter the beta cell, produce ATP, and stimulate insulin release
Lack of liver glycogen synthase
Type 0 Glycogen storage disease; unable to store glucose as glycogen, meaning don’t have stores to raise glucose when fasting; fasting hypoglycemia; hyperketonemia (high ketone bodies); hyperglycemia after eating due to inability to store excess glucose and lactic acidemia because the excess glucose will go through glycolysis; treatment: feed uncooked corn starch, which slowly releases glucose from digestive system
Lack of glucose 6 phosphatase
GSD type 1, von Gierke disease; unable to release degraded glycogen or gluconeogenesis products into the blood, fasting hypoglycemia; hepatomegaly due to increased glycogen in liver (G6P activates glycogen synthase and inhibits phosphorylase, lactic acidosis- high G6P goes through glycolysis, small amount of glucose gets out through debranching enzyme; no ketone bodies formed because fatty acid synthesis is favored, leading to gout and hyperlipidemia
Lack of lysosomal alpha-glucosidase activity
type 2 GSD, Pompe disease; used to cause death within 2 years; lysosomal storage disease- leads to inability to degrade glycogen and so glycogen builds up in the cell, impairing its ability to function; Lumizyme enzyme replacement therapy (has mannose-6-P tag)- effective for heart but not skeletal muscle
lack of debranching enzyme
type 3 GSD, Cori disease; fasting hypoglycemia, hepatomegaly (can’t break down all glycogen), elevated glycogen levels with abnormal structure (limit dextrins), inflamed liver
Lack of branching enzyme
type IV GSD, Anderson disease; fatal disease, low levels of non-branched, insoluble glycogen, cirrhosis (scarring of the liver), needs liver transplant
lack of muscle phosphorylase
type V GSD, McArdle disease; inability to use muscle glycogen as an energy source, weakness and cramping after exercise
lack of liver glycogen phosphorylase
type VI, Her disease; hepatomegaly (can’t break down glycogen), fasting hypoglycemia; could also be due to mutation in PKA, phosphorylase kinase or phosphorylase which affects its functioning
lack of muscle PFK-1
type VII GSD, Tarui syndrome; muscle can’t do glycolysis to make ATP; exercise intolerance, not able to use glycogen as an energy source
Fanconi-Bickel syndrome
GLUT2 mutations- affects liver, pancreas, kidney, intestines; glycogen accumulation in liver and kidney; fasting hypoglycemia, glucose in the urine, short stature, glucose can’t leave tissues
Beriberi
thiamin deficiency caused by alcoholism (alcohol blocks B1 uptake from the gut); Dry Beriberi: affects nervous system, since not enough energy for fuel, nystagmus (fast uncontrollable eye movements), confusion, tingling, speech difficulties; wet Beriberi: after cardiovascular system, increased heart rate, shortness of breath, CHF
Wernicke-Korsakoff syndrome
brain disorder due to lack of thiamin; Wernicke encephalopathy: confusion, loss of mental activity, loss of muscle coordination, nystagmus; Korsakoff syndrome (not reversible damage), inability to form new memories, loss of memory, confabulation, hallucinations
PDH deficiency
lactic acidemia (have to do more glycolysis), neurological problems because brain isn’t getting enough energy; usually X linked dominant because E1 subunit located on X chromosome
Kearns-Sayre Syndrome
deletion in mitochondrial DNA, affects nerves and muscle
Pearson Syndrome
deletion of mito DNA, affects the bone marrow
MERRF
Myoclonic Epilepsy and ragged red fiber disease; point mutation in tRNA lys
MELAS
mitochondrial encephalopathy, lactic acidosis, and strokelike episodes; point mutation in tRNA leu
Leigh disease
missense mutation in mito DNA; affects nerve and muscle, sometimes mutation occurs in ATP synthase
LHON
leber hereditary optic neuropathy; missense mutation in mito DNA; usually mutation in complex I; note: partial loss of activity in complex I, III, or IV leads to exercise intolerance
