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188 Cards in this Set
- Front
- Back
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Pick's Disease
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frontotemporal dementia, tau protein accumulation
aphasia, behavioral changes, personality alterations, depression, less memory prob then Alzheimers spares first temporal gyrus, ammons horn, substantia nigra |
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fronto - temporal dementias
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- progressive supranuclear palsy
- corticobasal degeneration - agyrophylic grain disease - demetia with Lewy bodies |
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Fibrillary tangles appear in
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Alzheimers
old age Jacob Creutzfeld supranuclear palsy (posttraumatic dementia) postencephalitic Parkinsonism |
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location of tau gene
phosphorylation leads to |
chr 17q21
DISRUPTION OF MICROTUBULE ORGANIZATION IN NEURONS |
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alpha synuclein
found in |
Lewy bodies in Parkinson
Lewy body dementia Alzheimer plaques Hallervorden Spatz syndrome |
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I cell disease
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resembles Hurler syndrom
early childhood growth retard./ cognitive retardation recurrent inf ( resp., otitis ) dwarfism hepatospleenomegaly heart valve enlargement |
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I cell disease mechanism
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lack off GlcNAc phosphotransferase.
Hydrolases out off Golgi not tagged with mannose-6-phosphate can't reach lysosomes, deactivated extracell. by PH: reduced phagocytosis accumulation off waste |
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macrophage off the CNS
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Migroglia
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reservoir for HIV in CNS and periph.
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CNS - Microglia
periph - dentritic cells in lymphknodes |
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Illnesses that cause Childhood cardiomyopathy
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alpha L Irunidase def
acid maltase def Carnithin uptake def LCAD def muscle glycogen phosphorylase def |
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fasting hypoglycemia and hypoketosis suggest
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block in fatty acid oxidation
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rate limiting step in catecholaminesynthesis
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tYROSINE ---> Dopa by tyrosine hydroxylase
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what digests triacylglyceroles if pancreatic lipase is missing
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lingual lipase
gastric lipase |
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Thromboxane a2
prod inhibited by Aspirin irrev. which is antithrombogenic effect of Aspirin |
prod by platelets
promotes their aggregation vasocon mobilizes intracell CA SM contraction, opposed by Prostacylcin |
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Prostacyclin PGI2
prod by vessel effect platelet effect |
endothelium
vasodilation inhibits aggregation |
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Leukotriene A4
produced by |
platelets leukocytes mast cells
heart & lung vasc tissues |
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Leukotriene A4 effects
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SM contraction
Bronchoconstriction Vasoconstriction incr. vasc permeability |
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Leukotriene B4
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chemotaxis
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PGE2
produced by effects |
most tissues esp. kidney
Vasodilation relaxes SM, but leads to uterine contraction used to induce labor |
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PGF2
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bronchoconstriction
uterine contractions |
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uses of Prostaglandins
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abortion, induction of labor
keep PDA open erectile dysfunction glaucoma |
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calcium oxalate stone
cystine stone |
Kidney stones
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calciumbilirubin stone Pigment stones found in
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hemolytice anemias, gallbladder
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signs of ketoacidosis
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Polyuria, dehydration thirst
hyperglycemia, glucose in urine => diuresis osmotic ( water follows ) CNS depression, Coma Decreases Plasma bicarbonate potential depletion of K( masked) Acetone breath |
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Aldose reductase
in diabetics in galactosemia |
forms sorbitol from glucose => Cataracts
forms galactidol from galactose => cataracts |
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Galactosemia sympt
classic form / uridyltransferase missing |
hepatomegaly cirrhosis, renal failure, cataracts, and brain damage
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norm HbA1c
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4- 5,9% of Hemoglobin
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bleeding, pancytopenia, bone erosions / fractures, hepatosplenomegaly
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Gaucher,
def.Glucocrebrosidase crumbled paper Macrophages |
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Km
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substrate concentration at half max velocity shows affinity of enzyme to substrate, cannot be altered by s or e concentration
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Km high means
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affinity low
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mitochondrial enzymes in urea cycle
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carbamoylphosphate synthetase
ornithine Transcarbamoylase |
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ketogenic aas
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leucine
lysine |
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glucogenic & ketogenic aa
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phenylalanine
isoleucine threonine tryptophane tyrosine |
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alphaketoglutarate dehydrogenase
oxo glutarate dehydrogenasemetabolism off |
lysine degradation
TCA cycle tryptophan metabolism |
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propionic acid pathway
metabolism off |
( V(o)mit)
valine methionine isoleucin threonine odd-carbon fatty acida |
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only two enzymes that use B12
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methylmalonyl CoA mutase
( Krebs )=> succinyl cOA N-methyl THF homocysteine methyl transferase => THF + Methionine from Homocysteine+ MethylTHF ( Folate metabolism and regenerating SAM ) |
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MCC for B12 def
B 12 stored def develops slowly |
pernicious anemia ( lack intrinsic factor parietal cells)
chron. pancreatitis gastric resection aging vegetarian diet parasite from raw fish D.latum |
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B 12 def symptoms
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megaloblastic anemia
periph. neuropathy homocysteinuria methylmalonic aciduria |
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Folate def
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megaloblastic anemia
homocysteinuria develops in 3-4 months neural tube defects in fetus |
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MCC Folate def
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pregnancy
alcoholism severe malnutrition |
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what all contains heme
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myoglobin
hemoglobin cytochrome electron transport chain p450 catalase peroxidas guanylate cyclase |
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Vit B6 def
Pyridoxine |
associated with isoniacide ther in TBC
leads to sideroblastic anemia with ringed siseroblast neccessary for ALA synthase in heme synthesis from Glycine+ succinylCoa |
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Iron def. anemia
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microcytic hypochromic anemia
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Causes of sideroblastic anemia
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lead poisoning
Vit B6 def |
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tissues insensitive to Insulin
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Brain
RBCs |
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Insulin effects ( fed state )
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fill glycogen stores then
fatty acid synthesis Triglyceride synthesis entry of Glucose in adipose + muscle |
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RbCs metabolism
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always anaerobic
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fast state hormones
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Glucagon
epinephrine |
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effects of glucagon epinephrine in fasting state
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glycogen degrad. in liver
gluconeogenesis in liver both glucagon release of aa from muscleand fatty acids from adipose via epinephrine aa give carboskel and fa give ATP for gluconeogenesis |
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prolonged fast
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glucagon + epinephrine high
rapid lipolysis => excess Acetyl CoA =>ketone synthesis lipids and ketones increased in blood muscle uses fa as fuel brain uses ketone bodies sparing proteins RBCs always use glucose ! no mitos |
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ketones are used in starvation by
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cardiac
resting skelettal muscle brain |
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fatty acids are used in starvation by
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cardiac muscle ( also in fed state ! )
skeletal muscle liver adipose |
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Liver energy sources in fed state
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mainly excess amino acids the glucose !!
transferes Glu into glycogen and fa into triglycerides then VLDL |
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carbon skeletons for gluconeogenesis from
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amino acids
lactate glycerol |
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location of lipoprotein lipase
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endothelium cap bed adipose
induces fa release from VLDL |
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acetyl CoA in fasting used for
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TCA
ketone bodies |
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normal blood glucose
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4-8 mMol
70-140 mg/dl |
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GLUT 2
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hepatocytes + pancreatic beta cells
low affinity captures excess glc for storage |
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GLUT 4
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adipose and muscle
number increased by Insulin translocation stimulated by excercise indep from Insulin |
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Glut 1 + 3
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baseline glucose uptake,
brain nerves RBCs Vmax at normal glc level |
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glucose used in adipose tissue for
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formation of DHAP
converted to Glycerolphosphate as skelleton for triglycerides |
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Glycolysis takes place in ?
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Cytoplasm
|
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Glucokinase is found in ?
and is activated by |
Liver
pancreatic Beta cells Insulin activated |
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PFK 2 is activated / deactivated by ?
Fructose-2,6 -Bisphospate stimulates ? |
Insulin/ Glucagon
PFK 1 |
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PFK-1 is stimulated by
inhibited by |
F-2,6 BP
AMP stimulate Citrate, ATP inhibit |
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Aldolase
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Fructose 1,6 BP to
DHAP and Glyceraldehyde 3-p |
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2,3 BPG
increased in deficient in transfusion leads to O2 trapping ! |
in RBCs via mutase from 1,3 BPG
decreases affinity of HbA to O2 => unloading in tissues increased in high altitude COPD Chronic anemia |
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what replenishes 2,3 BPG ?
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inosine
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High altitude adaptation
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hypervent
resp. Alkalosis initial lower P50 for hgb incr. glycolysis incr. 2,3 BPG restores P50 inc hemoglobin + hematocrit ( days ) |
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which has higher affinty to O2
HbA or HbF ? |
HbF
does not bind 2,3BPG to well |
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MCC hemolytic anemia
2nd MCC |
G6PDH
Pyruvatekinase def |
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GLycerol-3-p needed for
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glycerol shuttle for electron transport chain ( to FADH2)
triglyceride synthesis |
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glycerol-3-P comes from ?
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DHAP + NADH via G-3-P dehydrogenase to Glycerol-3_P
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Electron shuttles for NADH to ETC ?
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Malate shuttle : NADH + OAA =>Malate+NAD and reverse in Mito
NADH+ DHAP => Glycerol-3-P + NAD add FAD inner mito membrane=> FADH2 + DHAP |
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ATP yield 1 glucose glycolysis via malate shuttle
via Glyc-3-P shuttle ( FADH2) |
8 ATP
6 ATP |
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Aldolase reductase
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in lens metabolizes accumulated galactose to galactidol => cataracts
also converts glucose in diabetics to sorbitol in lens => osmotic damage => cataracts |
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Galactosemia
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def off Galactokinse or
Uridyl transferase later is more severe Cataracts Vomiting , diarrhea jaundice hyperbili liver dissease , cirrhosis lethargy mental retardation |
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Aldolase B
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Fructose 1-P => DHAP + Glyceraldehyde
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Sucrose is
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tablesugar
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fructose is metabollized where ?
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Liver + kidney via Fructokinase & Aldolase B
other tissues via hexokinase |
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fructose-1-P accumulation in ?
Sympt |
Aldolase B def.
severe hypoglycemia lactic acidosis Vomit etc prox renal tube disorder not noticed while breastfeeding |
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where is Pyruvate dehydrogenase loacted ?
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Mito
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Cofactors PDH
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Thiamine PP
Lipois acid Coenzyme A from pantothenic acid FAD from riboflavin NAD fromNiacin ( synth from tryptophan ) |
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Hartnup's disease
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autosomal recessive
disorder in absorption of neutral amino acids (particularly tryptophan that can be, in turn, converted into Serotonin, Melatonin and Niacin fotosensitivity failure to thrive ataxia nystagmus tremor |
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PDH def
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lactic acidosis
brain damage early death x-linked dominant rare |
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Wernicke Korsakoff
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C-onfabulations
O - phthalmoglegia M - emory loss A - taxia congestive Heart failure wet beri beri Thiamine def B1 affects brain + muscle |
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Electron shuttles to inner mito
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OAA + NADH => MALATE + NAD
to NADH and Complex 1 in ETC DAHP + NADH=> Glycerol-3-P + NAD to FADH2 in ETC |
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Pyruvatekinase def
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2nd MCC chronic hemolysis
incr. 2,3 BPG no HEinz bodies |
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Cofactors PDH
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Thiaminpp
Lipoic acid NAD niacin B3 FAD riboflavin B2 Coenzyme A pathotenate |
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3 irreversible steps in Glycolysis
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Hex/Glucokinase
PFK1 Pyruvatekinase |
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Where is succinatedehydrogenase located + function
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inner mitochondrial membrane
TCA ( succinate=> Fumarate) at same time Complex 2 of ETC |
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Alpha ketoglutarate DH coenzymes
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Coenzyme A
Lipoic acid Thiamine B1 Niacin B3 NAD FAD riboflavin B2 |
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Citrate shutlle
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leaves Mito from TCA to fatty acid synthesis in cytosol
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SuccinylCoA does
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activate ketone bodies
react with GLycin in heme production react to succinate via SCoAsythetase to Succinate prod GTP |
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Thiamine is a cofactor in
|
PDH
Alpha -ketoglutarate DH Transketolase alpha keto acid dh |
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Hypoketotic hypoglycemia is a sign of
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Carnithin palmitoyl transferase 1 deficiency with
incr carnithine hepatomegaly muscle weakness aut rez |
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Maple syrup urine disease think off
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trees & branches !
Brached chain alpha ketoacid DH deficiency or Cofactor Thiamine |
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tetrahydrobiopterin is a cofactor for
|
Phenylalaninehydroxyase
Tyrosine hydroxylase Tryptophanhydroxylase NO synthase |
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bilirubin glucoronyl transferase forms
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water soluble gucuronide bilirubin for excretion
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Purines
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Pur as gold
Adenine Guanine both in DNA+RNA Others not in DNA/RNA : xanthine Hypoxanthine Uric acid |
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Pyrimidines
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Cut the py
Cytosine Uracil only in RNA ( U R ) Thymidine only in DNA |
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Desaminierungsprodukt of
Guanine is Adenine |
Xanthine
Hypoxanthine |
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Nucleoside of Hypoxanthine is
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Inosine
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COmplementary pairs in DNA
and number of bonds ) which kind ? |
A -T : 2 hydrogen bonds
G - C : 3 hydrogen bonds |
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CHargaff rules
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DNA is
antiparallel complementary A-T G-C Purine amount = pyrimidine amount |
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G-C rich DNA is called ?
had which characteristics ? |
Z-DNA and left handed double helix
instead B-DNA and right handed watson Crick high Tm cause 3 bonds !! |
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size in DNA double helix
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complete turn : 3nm
with 2 nm |
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what denatures DNA ?
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heat
alkaline PH chemicals : formamide urea disrupts hydrogen bonds between bases |
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Tm of DNA
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melting tem, temp at which 50% of hydrogen bonds denatured
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When is DNA denatured
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hydrogen bonds broken
high absorbtion at 260 nm |
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negatively supercoiled DNA is ?
who changes supercoiling ? |
looser then Watson Crick nec. for biologic reactions
Topoisomerase |
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What is a nucleosome ?
How big is it ? |
packaging unit off CHromatin :
HIstone octamer ( H2a,H2b, H3, H4 two of each ) with DNA wound around 10 nm |
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Histones are rich in
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lysine and arginine
basic aa positively charged bind to neg charged DNA |
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H1 histone is found on ?
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Linker DNA between NUcleosomes
packs them in 30nm solenoid fiber |
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which is packed tighter
Euchromatin or Heterochromatin ? |
Heterochromatin tight and inactive
Euchromatin corresponds to 30nm fiber |
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CHromatin modifying activities for transcription are ?
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Histone acetylation and
Histonephosphorylation ( fills pos charge => loosening from DNA ) |
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CHromosome abnormalities are analysed in
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Karyotyping of metaphase chr +
banding of pro or prometaphase chromosomes |
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most condensed DNA
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mitotic
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deamination product of Cytosine is ?
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Uracil
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Quinolones inhibit ?
ex rx |
Prokaryotic topoisomerase II
ex : Nalidixic acid Ciprofloxacin Norfloxacin RX : gomorrhea upper & lower urinary inf |
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Telomerase activity ?
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reverse transcriptase activity
replaces lost telomeres in germ and stem cells lsot in somatic cells contains short RNA template high in cancer cells ! |
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reverse transcriptase in retroviruses inhibited by
|
ddC. ddI. AZT
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Polymerase gamma
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mitochondrial !
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DNA polymerase III and I
|
prokaryotic
I has 5-3 exonuclease and excises primer |
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the template DNA is read in which direction ?
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3"- 5 "
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The mRNA is synthesized in which direction?
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5 '- 3'
antiparallel and complementary |
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RNAs and their polymerases starting with most abundant?
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rRNA - polymerase I
tRNA - polymerase III mRNA - polymerase II HnRNA = pre mRNA - pol II (eu) snRNA = splicing - pol II (eu) ribozymes |
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what is a snurp ?
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small nuclear RNA + protein
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RNA polymerase II
moves in direction synthesizes mRNA in |
3'- 5'
5'- 3'direction |
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DNA polymerase III / delta synthesizes DNA in whhich direction ?
|
5'-3'
|
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eukaryotic DNA polymerases
|
delta - leading
alpha - lagging gamma - mitochondrial beta & epsilon - DNA repair |
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quuinolones inhhibit what ?
|
prokaryotic topoisomerase II
|
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prokaryotic DNA polymerases
|
III - leading and lagging
I - removal of primers replace ment of RNA with DNA primase does RNA primer |
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coding strand versus template strand
|
template used for RNA synthesis
coding strand not used same sequence as RNA mol only with Thymine. also calleed antitemplate |
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base sequence of a gene is given from which strand
|
coding !!! in 5'-3'direction
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ribosome translates mRNA in direction ?
aa produced in which ? |
5'-3'
aa from amino - carboxyl end NH2 - COOH |
|
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all base sequences are written 5'- 3'!!!!
RNA never has T in it except one in TRNA |
5'TAGC 3'
|
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rifampin inhibits ?
|
rho factor needed for termination of transcription in prokaryotes
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Actinomycin D mech of action ?
|
binds to DNA inhibiting ALL transcription :
prokaryotic alpha2beta beta eukaryotic RNApol II |
|
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prokaryotic RNA polymerases
|
ONE ! RNA pol ALpha beta beta'
sigma factor for initiation on promoter rho factor for termination |
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RNA pol in eukaryotes
|
pol I - ribosomal, in nucleolus
pol II - mRNA/ hnRNA nucleoplasm pol III - tRNA /snRNA/5SrRNA in nucleoplasm TFIID helps pol II |
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alpha amanitin inhibits ?
|
RNA polymerase II
|
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promotor contains
|
TATA / pribnow box
-35 sequence |
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what is the AUG codon ?
|
start codon for prok prot synthesis
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what is shine Dalgarno sequence ?
|
on mRNA of prok binds ribosomes
complementary to 16s rRNA of prokaryotic ribosome ! |
|
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monocystronic mRNA
polycystronic mRNA |
transcribed from single gene info for single protein (all euk. are monocystronic )
contains info from several genes and codes for several prot only in prokaryotes ! |
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posttranscriptional processing takes place in ?
|
nucleus of eukaryotic cells
|
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posttransciptional modifications of mRNA are ?
|
7-methylguanosinecap on 5'end prevents degradation and is ribosome binding site
poly A tail on 3'end prevents degradation and facilitates move to cytoplasm |
|
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poly A tail addition signal
|
AAUAAA
endonuclease cuts at 3'end and adds 200 As |
|
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are there RNA without poly A tail ?
|
histone mRNA
|
|
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mechanism of beta thalassemia
|
mutations in splicing cites for beta globin mRNA !
|
|
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examples of alternative splicing
|
troponin T
tropomyosin immunoglobulins from unstimulated membrane bound versus stimulated secreted from B lymphocytes |
|
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eukaryotic ribosomal units
|
60s 40s
28s 18s 5.8s 5s makes 80 S |
|
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prokaryotic ribosomal subunits
|
50 S & 30 S
23S 16s 5s makes 70 S |
|
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triplet repeat expansion examples
|
huntington + spinocerebellar ataxia both CAG ( aut -dom )
fragile X myotonic dystrophy spinobulbar musc atrophy ( x-linked ) Friedreich ataxia |
|
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Friedreich ataxia
|
aut rec
Friedreich's ataxia is the result of nerve degeneration caused by a trinucleotide repeat expansion mutation.GAA chr 9 < 25a stumbling, hearing + vision loss sluring speech, heart prblems, diabetes |
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Fragile X
|
aut dom with reduced penetrance
intellectual disability elongated face, large or protruding ears, flat feet, (macroorchidism), and low muscle tone Expansion of the CGG codon leads to methylation and silencing |
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spinobulbar musc atrophy
|
CAG repeat expansion
Androgen receptor mutation on x chr - X linked rec speach, breathing,swallowing difficulty lower motoneuron : muscle wasting decr. reflexes impotence etc |
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stop codons
|
UAA
UAG UGA |
|
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start codon
|
AUG
Methionine always in euc formylmet in proc |
|
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transition ?
|
point mutation replacing purin-pyrimidine
with purin- pyr |
|
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Transversion
|
point mut
replces pur-pyr with pyr - pur base pair |
|
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Alpha thalasemia mechanism
|
unequal crossover delteion on chr 16
|
|
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deletions in crossover during meiosis examples
|
Cri du chat Chr 5
Alpha thalassemia |
|
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Ef II inhibited by
|
Pseudomonas ,Diphtheria toxins
|
|
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cystic fibrosis cause
|
deletion oh Phe in F508
abnormal prot folding abnormal chloride channel protein = CFTR aut rec |
|
|
proteins translated on RER ribosomes are ?
|
secreted prot
prot inserted in cell membrane lysosomal enzymes |
|
|
proteins translated on free ribosomes are ?
|
cytoplasmic prot
mitochondrial prot those encoded by nuclear genes |
|
|
ubiquination
|
marking of prot for degradation and digestion by proteasomes
|
|
|
what are molecular chaperones ?
|
aid in prot folding
calnexin biP transfer mitochondrial prot( from nuclear genes) into mitochondrium |
|
|
what directs enzyme protein to lysosome after translation ?
|
phosphorylation of mannose residues
|
|
|
What directs ribosomes / proteins to RER after translation beginns in cytoplasm ?
|
N-terminal hydrophobic signal sequence
signal recognition particle ribosome attaches to RER |
|
|
diseases with mutations in splice sites
|
Gaucher
Tay -Sachs beta Thalassemia |
|
|
disease with segment deletion mutations ?
|
Alpha thalassemia chr 16
Cri du CHat chr 5 Ip36 |
|
|
protein glycosylation in Golgi / RER
|
N-linked at asparagine needs Dolchilol
O-linked at serine and Threonine |
|
|
Lysosomal storage disease
|
Tay - Sachs - ganglioside HEXA
|
|
|
I cell disease
MLII aut rec |
Mukolipidosis
GlcNac phosphotransferase in Golgi missing no mannose-6-p, acc of enzymes in extracell space ,+inclusion bodies in cells s: bonde deformities coarse facial features hepatospleenomeg clouded cornea mental retard. short trunk dwarfism resp infections congest. heart failure |
|
|
hydroxyproline is unique to
Deficiency of what causes lack of hydroxylation in RER ? |
collagen
cofactor ascorbate ! neede for hydroxylases in RER |
|
|
Cu is needed by enyzymes
|
lysyl oxidase ( collagen fibrils)
Dopamine beta hydroxylase superoxide dysmutase cytochrome c oxidase |
|
|
CHemotactic factors
|
IL 8
IFn-gamma C5a |
|
|
normal anion gap acidosis
causes |
HARD-UP
Hyperalimentation Acetazolamide ( Carbonic anhydrase inhibitors) Renal tubular acidosis Diarrhea Ureteroenteric fistula Pancreatico-duodenal fistul |
|
|
Azotemia
|
decreased GFR oliguria anuria
increased BUN + Creatinine and other nitrogen rich compounds prerenal, renal, postrenal faigue, tachycardia, dry mouth Uremic frost , edema, thirst |
|
|
prerenal Azotemia
|
decreased CO => decr. renal blood flow
BUN : Cr > 15 as BUN is filtered AND reabsorbed !! |
|
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renal Azotemia
|
leads to uremia
BUN: Cr normal < 15 prox tubule damaged => no reabsorbtion BUN => excreted like crea |
|
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postrenal Azotemia
|
blockage postrenal
incr. BUN reabsorb via pressure BUN : Cr > 15 |
|
|
amyloidosis diagnosis histo
|
apple green birefringence
Congo red stain |
|
|
neurological Amyloid
|
ALZHEIMER
hUNTINGTON PARKINSON CREUTZFELD JACOB PRION DISEASE KURU FATAL FAMILIAL INSOMNIA BOVINE SPONGIFORMENCEPHALOPATHIE |
|
|
aMYLOID TYPES
|
AL light chain from Ig ( BEnce JOnes prot ) multiple myeloma
AA prot from liver PrP prion derived BETA 2 MICROGLOBULIN - in chronic hemodialysis BETA AMYLOID - Alzheimer TRANSTHYRETIN |
