Block 2 exam (bio+gene) Flashcards
Lypophilic “LieS are SPACeD TogetheR, be NiCeR” vs. Hydrophilic “Need MASHED Potatoes Cooked In Gravy & Lamb fAt”
Lipo= Steroid hormones (progesterone, aldosterone, cortisol, vitamin D), Thyroid hormone (thyroxine), Retinols (retinoic acid, retinol) & Receptors in the cytoplasm + nucleus
hydro= AA derived (Noreepi/epi, histidine, Methionine, Serine, dopamine), Polysaccharides (cytokines, glucagon, insulin), Lipid metabolism (Acetylcholine)
GCPR general activation principle “GP’s LECture ABout the GI”
A ligand binds (extracellularly) to the receptor causing a confirmational change in the receptor —> this allows a G protein to bind to the receptor (intracellularly) & swap GDP for GTP to activate —> The G protein then dissociates into alpha & beta/gamma (stable+ anchored to the membrane) subunits. –> The G-alpha subunit can undergo further casades into
Gs (alpha) –> + AC –> increase cAMP –> increase protein kinase A (increases glycogen breakdown into glucose via serine/threonine kinase phosphorylation od glycogen phosphatase (+) & synthase (-) (aka glycogenolysis + hypoglycemia))
Gi (alpha) –> inhibits AC –> decrease cAMP –> NO protein kinase A
Gq (alpha) –> + phospholipase c –> cleaves PIP2 into DAG/diacylglycerol (membrane bound which forms PKC) & IP3/inositol triphosphate (cytosol, which increases Ca2+ release from the SR, to + PKC)
General RTK activation “Real Tough Kids, are LADs that Be CAPTains with INK SMears of 2 SHarks”
Ligand binds a subunit (extracellularly) & triggers dimerization and a confirmational change in the beta subunits to cause auto/cross-phosphorylation —> this increases kinase activity because the phosphorylated tyrosine residues allow signal molecules with SH2 binding domains to bind to the RTK then undergo either PI3K or MAPK depending on the effector involved
RTK insulin MAPK cascade “I’M An IRS MEmbERR”
Gereneral RTK activation activation happens & the autophosphorylation of the tyrosine residues attracts the IRS (insulin receptor substrate) —> the IRS recruits RAS+GTP (active) –> this increases kinase activity forming RAF + MAP KKK –> MEK + KK –> ERK +K which can then enter the nucleus and binds ELK to transcribe genes for cell growth and proliferation
RTK insulin PL3K cascade “Rough Tough Kids, CAn Really PaCk a PunCh, PoweD!”
RTK general activation happens —> the cross/auto phosphorylation of the tyrosine residues attracts the IRS (insulin receptor substrate) –> the IRS then recruits Phospholipase C which cleaves PIP2 into IP3 (increases intracellular calcium for smooth muscle contraction + activate PKC) and DAG (makes PKC acts on transcription factors for cell growth/proliferation)
Lipophilic “LieS are SPACeD TogetheR, be NiCeR” vs. Hydrophilic “Need MASHED Potatoes Cooked In Gravy & Lamb fAt”
Lipo= Steroid hormones (progesterone, aldosterone, cortisol, vitamin D), Thyroid hormone (thyroxine), Retinols (retinoic acid, retinol) & Receptors in the cytoplasm + nucleus
hydro= AA derived (Noreepi/epi, histidine, Methionine, Serine, dopamine), Polysaccharides (cytokines, glucagon, insulin), Lipid metabolism (Acetylcholine)
NON-RTK (JAK-STAT) activation “JAK TooK APpleS So Sweet Down Past the Jagged Gorge”
A ligand binds the receptor and causes dimerization —> the dimerization triggers the tyrosine kinase containing domains (JAK) to cross/autophosphorylate —> this forms SH2 binding domains which attract STAT proteins to bind, dimerize, and phosphorylate –> The STAT proteins can then act within the nucleus as transcription factors to regulate JAK-STAT-associated genes
Galactosemia
Classical “CaGed Bears Have Fierce Jaws & Claws” vs Galactokinase def “Gary’s Kool CaST”
Classical: Usually happens after breastfeeding (introducing lactose to the baby) because it has a deficient galactose-1-p uridylyltransferase (means galactose-1-p can’t be converted to glucose-1-p, so it accumulates, reducing ATP and stopping gluconeogenesis & glycogenolysis)
Look for: cataracts, hepatomegaly, failure to thrive, & jaundice
Galactokinase def: is due to def galactokinase causing galactose to accumulate & be converted into galactitol via aldose reductase
Look for: cataracts, no social smile, and no tracking objects, otherwise it’s asymptomatic
fructosuria
Hereditary fructose intolerance “FAtHer JoHn’s Hell for Fucking Small Children” vs Essential fructosuria “EFFective Hemp FArMs”
HFI: Deficient Adolase B (causes an increase in fructose-1-p, reducing ATP and stopping gluconeogenesis & glycogenolysis)
Look for Hypoglycemia, Jaundice, Hepatomegaly, Seizures, Fail to thrive, & Cirrhosis
Treatment = Avoid sorbitol, fructose, & sucrose
EF: deficient fructokinase (fructose accumulates)
Look for: high fructose levels in the blood, but because hexokinase can metabolize fructose, this condition is asymptomatic and doesn’t need treatment
Pompe (glycogen/lysosomal storage disease) “Pompe Can Always Degrade & Hurt the Heart”
Deficient alpha-glucosidase means it can’t breakdown glycogen, and the buildup causes hypotonia, cardiomegaly, & elevated creatine kinase in the blood
Cori disease (glycogen storage) “I CAn Work 1-6 Hrs on Cardio”
A deficient alpha (1,6) glucosidase enzyme (no glycogen breakdown) causes milder hypoglycemia, weakness, & cardiomyopathy
McArdles (glycogen storage) “MC Donalds Makes Crispy Fries & Marvelous Meats”
A deficient Myophosphorylase (glycogen can’t be broken down in skeletal muscle) causes fatigue, muscle cramps, & myoglobinuria (rusty/dark pee)
Make sure to eat complex carbs and simple sugars
lactic acidosis in infants due to:
Pyruvate Dehydrogenase deficiency
Pyruvate Decarboxylase
PDH= build up of pyruvate gets shunted by Lactate DH to lactate & ALT to alanine leading to lactic acidosis
treat with a ketogenic diet (leucine & lysine)
Pompe’s
“PoMpe Always Hurts My heart”
Deficient alpha-1,6 glucosidase (causing an increase in glycogen in lysosomes)
Causes:
- Hypotonia (floppy baby)
- muscle weakness
- cardiomegaly (dead by 1 yr :( )
- Macroglossia
Classical galactosemia
“CaGed Bears Have Fierce Jaws & Claws+
Def galactose-1-p uridyl transferase
Causes
- Cataracts
- Hepatosplenomegaly
- Fail to thrive
- Begins with breastfeeding
- Jaundice
Galactokinase def
def galactokinase = build-up of galactitol via aldolase
= Cataracts + no social smile + can’t track objects
Hereditary fructose intolerance
“FAther JoHn’s in Hell for Fucking Children”
Def Aldolase B (buildup of glucose-1-p)
causes:
- Hepatomegaly
- Seizures
- Jaundice
- Cirrhosis
- Fail to thrive
Essential fructosuria
Def fructokinase (build-up of fructose causing high levels of hexokinase via glycolysis)
Reducing agents in the urine
Von Gierks
“SHEiLD”
Def glucose-6-phosphatase
Causes
- doll face (fat cheeks)
- Hepatomegaly
- Severe fasting hypoglycemia
- High lactic acid, uric acid, & Cholesterol
- Excess liver glycogen
Avoid fasting/frequent feeding/high sugar diets
Signalling proteins
Gas “FLAT CHAMP’s CHuGG”
Gai “SMAll DP”
Gq “GOAT HAG”
Gas= FSH, LH, ADH (V2), TSH, CRH, Histamine (H2), ACTH, MSH, PTH, Calcitonin, GHRH, hCG, Glucagon + beta-adrenergic receptors
Gai= Somatostatin, M2, alpha-2, D2, Prostaglandins
Gq= GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1), Angiotensin II, Gastrin
Glut (1-2 SGLUT) transporters
G1/3= BBB for the brain and RBCs (High affinity under any conditions)
G2= Beta cells of the liver and pancreas (low affinity)
G4= Insulin dependent fat & muscle
G5= high affinity for fructose
SGLUT 1= Gut
SGLUT 2= Kidney
Insulin RTK IP3K Pathway
Ligand binds the RTK receptor (alpha subunit), —> triggers a conformational change in the beta subunit causing autophosphorylation of the tyrosine residues —> this attracts an IRS (insulin response substrate) to bind and form an SH2 binding domain —> IP3Kinase binds the SH2 and converts PIP2–> PIP3 —> PKB =
- +mTOR genes (protein phosphate to phosphorylate) = +glycogen synthase & - glycogen phosphorylase (+ glycogenesis, - glycogenolysis)
- Increase GLUT4 #’s
- phospho/activation of SREBP = + glucokinase, PD, LPL, FAS, ACC (+ Glycolysis & Fatty acid synthesis)
- +PDE = low cAMP –> no PKA = no lipolysis
Insulin RTK MAPK Pathway
Ligand binds the RTK receptor (alpha subunit), —> triggers a conformational change (dimerization) in the beta subunit, causing autophosphorylation of the tyrosine residues —> this attracts an IRS (insulin response substrate) to bind and form an SH2 binding domain —> Grb2 binds to SH2 & attracts RAF+GTP (active) —> RAF X3 MAPK —> MEK X2 MAPK —> ERK MAPK —> translocates into nucleus and binds ELK to increases transcription factors for cell growth and division
JAK-STAT
Ligand binds and causes conformational change (dimerization) in receptor –> this triggers Jaks to autophosphorylate and prep a phosphate for STAT —> STAT binds to SH2 and is phosphorylated (activated) —> STAT separates from the receptor, dimerizes, then translocated to the nucleus to bind transcription factors (increase transcription/expression of JAK-STAT regulated genes)
