5/4 Biochemistry/ Mixed Flashcards
Short non-coding RNA sequences (micro RNA and small interfering RNA) role in gene silencing
Induce posttranscriptional gene silencing by base-pairing with complementary sequences within target mRNA molecules
Hormone-sensitive lipase
Found in adipose tissue
Functions to drive the breakdown of stored triglycerides into free fatty acids and glycerol
During times of starvation, this enzyme provides substrated for hepatic gluconeogenesis and ketone body formation
Stimulated in response to stress hormone (catecholamines, glucagon, ACTH), inhibited by insulin
NOTE: brain can only use ketone bodies/glucose (FFA do not cross BBB), RBC only use glucose (no mitochondria
Hereditary fructose intolerance
Aldolase B deficiency
Failure to thrive, jaundice, hepatomegaly
Lynch syndrome (hereditary nonpolyposis colon cancer)
Autosomal Dominant
Defective DNA mismatch repair (MSH2, MLH1 mutations) > MutS and MutL homologs
Acetyl-CoA’s role in gluconeogenesis
Acts as an allosteric activator by increasing the activity of pyruvate carboxylase (pyruvate to oxaloacetate). Note, this only occurs when Acetyl-CoA levels are high. When Acetyl-CoA is low, pyruvate is shunted toward Acetyl-CoA production, preventing the cell from becoming energy depleted
Sucrose
Fructose + Glucose
Avoid in aldolase B deficiency (hereditary fructose intolerance)
Most common genetic cause of hyperhomocysteinemia (increased thrombotic events)
MTHFR deficiency (methylene tetrahydrofolate reductase)
also deficiencies of Vit B12, 6, and folate
More than one codon can code for a particular amino acid
Genetic code is degenerate
Wobble
Secondary lactate deficiency
Can occur after inflammatory (celiac disease) or infectious (giardiasis) processes damage the microvilli of the small intestines
Abdominal distension, cramping, flatulence, diarrhea
Conversion of norepinephrine to epinephrine
Phenylethanolamine-N-methyltransferase
Adrenal medulla
Cortisol increases converstion
(no pituitary= no ACTH= no cortisol)
Galactosemia
Impaired galactose-1-phosphate metabolism
Deficiency of galactose-1-phosphate uridyl transferase
Vomiting, lethagy, failure to thrive soon after breastfeeding
Scurvy (vit C deficiency)
perifollicular hemorrhages, myalgias, subperiosteal hematoma, gingivitis, hemarthrosis, petechial hemorrhages, impaired wound healing, weakened immune responses
Base excision repair
Repairs non-bulky DNA base alterations (depurination, alkylationmoxidation, deamination)
Excessive consumption of dietary nutrutes can promote deamination
Glycosylases, endonuclease, lyase DNA polymerase, ligase
Cofactor for oxaloacetate to phosphoenolpyruvate during gluconeogenesis
GTP (synthesized by succinyl-CoA synthetase during the conversion of succinyl-CoA to succinate in the Citric acid cycle)
During gluconeogenesis, phosphoenolpyruvate carboxykinases uses GTP to synthesize phosphoenolpyruvate from oxaloacetate
Wernicke encephalopathy
Opthalmoplegia, ataxia, confusion (coma, death)
Foci of hemorrhage/necrosis in mammillary bodies
Chronic thiamine (B1) deficiency
Dx: baseline erythrocyte tranketolast activity is low but increases with addition of thiamine pyrophosphate
Treat with thiamine supplementation and glucose infusion
Smooth ER
Contains enzymes for steroid and phopholipid biosynthesis
All steroid producing cells (e.g. cells in the adrenals, gonads, and liver) contains a well developed smooth ER
Methylmalonic acidemia
AR, organic acidemia
Deficiency of methylmalonyl-CoA mutase
Metabolic acidosis, hypoglycemia, ketones, hyperammonemia
Elevated urine methylmalonic acid and propionic acid
Lethargy, vomiting, tachypnea
Pompe disease
Deficiency of acid-a-glucosidase
Infancy, cardiomegaly, macroglossia, muscular hypotonia
Glucose-6-phosphate dehydrogenase (G6PD deficiency)
Hemolytic anemia after infections (pneumonia, viral hepatitis), consumption of fava beans, meds (primaquine, sulfa drugs)
G6PD converts glucose 6-phosphate to ribulose-5-phosphate, 2 NADPH are produced (pentose phosphate pathway)
Major source for cellular NADPH
Necessary for reducing glutathione (preventing oxidative damage), biosynthesis of cholesterol, fatty acids, steroids
Spinal muscular atrophy
Mutation in SMN1 gene
impaired assembly of snRNPs in lower motor neurons
Flaccid paralysis dye to degeneration of anterior horn cells
Familial erythrocytosis
B-globin mutation > reduced binding of 2,3-BPG, results in loss of positive charge in pocket, causes hemoglobin A to resembled fetal hemoglobin (binds oxygen with a higher affinity, due to inability to interact with 2,3-BPG
GLUT-4
Skeletal muscles, adipocytes
Insulin-sensitive
What causes cataract formation in a patient with galactosemia
(Galactokinase deficiency)
Galactitol accumulates in lens of patients with galactosemia and causes osmotic damage leading to cataract formation.
Galactitol is formed from excess circulation galactose in galactosemia by aldose reductase
Glucagon second messenger system mechanism
Exerts it effects via G-protein coupled receptors using adenylate cylase second messenger system, cAMP, protein kinase A
TSH, glucagon, PTH receptors all use this system!
Lesch-Nyhan syndrome
- deficiency of HGPRT
- increases the demand for de novo purine synthesis
- activity of PRPP aminotransferase must increase to supply a sufficient quantity of purine nucleotides
Cofactor for transaminases
Pyridoxine (Vit B6)
Transamination reactions (N) typically occur between an amino acid and an a-keto acid
Amino group is transferred to a-keto acid from amino acid and the a-keto acid thereby becomes an amino acid
Glutamate reacts with oxaloacetate to form asparate and a-ketoglutarate
Ataxia-telangiectasia
AR, defect in DNA-repair genes
DNA is hypersensitive to ionizing radiation
Cerebellar ataxia, oculocutaneous telangiectasias, repeated sinopulmonary infections, increased incidence of malignancy
Rx of moderate-severe allergic asthma
Anti-IgE antibodies given as SQ injection (Omalizumab)
Helps to reduce dependency on both oral and inhaled steroids
Most important mediator of sepsis
TNF-a (produced by activated macrophages), induces a systemic inflammatory response
(IL-1 and IL-6 are also involved)
Theophylline intoxication
Seizures, tachyarrhythmias, nausea/vomiting, abdominal pain, diarrhea
Rx: activated charcoal, B-blockers, benzodiazepines/barbituates (seizures)
Best indicator of severity of mitral regurgitation?
Presence of audible S3
Indicates a high regurgitant volume and severe mitral regurg, left ventricular volume overload (reflects increased rate of left ventricular filling due to a large volume of regurgitant flow-reentering the ventricle during mid diastole)
Pulsus paradoxus
decrease in systolic blood pressure of >10 mm Hg with inspiration
seen in patients with cardiac tamponade (pericardial dx), severe asthma, COPD, constrictive pericarditis
Quanitified by the difference between systolic pressure at which Korotkoff sounds first become audible during expiration and the pressure at which they are head throughout all the phases of respiration
How do beta-adrenergic agonists control acute asthma/COPD?
Cause bronchial smooth muscle relaxation via increased intracellular cAMP
Drugs that have been shown to improve long-term survival in patients with heart failure due to left ventricular systolic dysfunction
Beta blockers, ACE inhibitors, angiotensin II receptor blockers, aldosterone antagonists
Stop codons
UAA, UAG, UGA
Cause releasing factor proteins to bind the ribosome and stimulate release of the formed polypeptide chain
Note: START = AUG
Colchicine
Inhibits tubulin polymerization into microtubules (cytoskeleton)
Used for acute Rx and prophylaxis of gout
SE: nausea, abdominal pain, diarrhea
Which artery supplies Broca’s area and Wernicke’s area
Middle cerebral artery
Broca= superior division
Wernicke= inferior division
