Biochem Block 3
Card Set Information
Biochem Block 3
Biochem block 3
Which Sphingolipidosis produce cherry red macula?
What enzyme is deficient in GM1 gangliosidosis?
What substrate accumulates
What enzyme is deficient in Tay-Sacchs?
What substrate accumulates?
What enzyme is deficient in Sandoffs?
What substrate accumulates?
N-acetylhexosaminidase A and B
GM2 ganglioside and globoside
In what sphingolipidosis are pain in lower extremities, reddish purple rash, and treatment with enzyme replacement possible?
Which sphingolipidoses produces lipid laden(crumpled tissue paper) appearance?
What local molecule released by active platelets promotes platelet aggregation and constriction of blood vessels in the area of injury?
Vascular endothelial cells produce what compound that prevents platelet aggregation and vasodilates blood vessels?
PGF2 is a constrictor or dilator of blood vessels?
PGE2 is a vaso- constrictor or dilator?
What enzyme produces Prostoglandins and Thromboxane A2?
What enzyme produces Leukotrienes?
What are the precursors to prostoglandins, thromboxanes and leukotrienes?
Linoeic acid(18 carbons)----arachidonic acid( 20C)
Conversion of Arachidonic acid to prostoglandins is done by what enzyme?
PG endoperoxide synthase (PGES)
What are the two isoenzymes of PG endoperoxide Synthase?
COX-1 and COX-2
What is the difference between COX 1 and COX 2?
COX 1 is expressed constitutively abundantly and is involved in maintenance of gastric mucosa, renal homeostasis and platelet aggregation
COX 2 is inducible involved in in heat pain and inflammation
What enzyme converts membrane lipid( phosphotidylcholine) to arachidonic acid?
What prevents the action of phospholipase A2 and COX-2?
What effect does aspirin have on platelet aggregation and cox 1?
irreversibly binds COX-1 and reduces platelet aggregation
What drug inhibits only COX-2?
What acts as a neutrophil chemotactic agent?
Leukotrienes LTC4, D4, E4 function to do what?
increase vascular permeability
contraction of smooth muscle
Endoperoxides give rise to what 3 distinct group of signalling molecules?
Prostocyclin--inhibit platel gatherin, vasodilation
Prostoglandin---pain, uterine tone, temperature
Thromboxanes- promote platelet aggregation, vasoconstriction
Heparin inhibits synthesis of what factors?
Warfarin inhibits the synthesis of what clotting factors?
Protein C, S, Vitamin K derived clotting factor--2,7,9,10
What is the rate limiting step for FA synthesis?
Acetyl coa Carboxylase
What is the rate determining enzyme for FA oxidation?
Carnitine acyl transferase I
Rate limiting step for HMP shunt?
G6PD--glucose 6 phosphate dehydrogenase
Rate limiting step for TCA?
Rate limiting step for glycolysis?
Rate limiting step for cholesterol synthesis?
HMG coA reductase
What is the rate limiting step for glycogen lysis?
Rate limiting step for gluconeogenesis?
Fructose 1,6 bisphosphatase
Rate limiting step for glycogen synthesis?
Why doesnt glucokinase have an allosteric inhibitor?
because it has a high Km/low affinity for glucose
acts as a glucose buffer in the blood
Which glucose transporter is insulin sensitive?
Which GLUT is needed for fructose transport?
What is the structure of Acetyl coA Carboxylase?
Desaturation of fatty acids occurs where?
What 2 components are used for desaturation of FA?
On the glycerol back bone what is the nature of FA on C1
C1 saturated FA
C2 Unsaturated FA
C3 sat or unsaturated
What is the source of NADPH for FA synthesis?
2 NADPH from HMP shunt
1 NADPH from malate to pyruvate
Fatty acid synthase produces what kind of FA?
What inhibits carnitine acyltransferase I?
How does liver synthesize Glycerol 3 Phosphate?
Using glycerol Kinase
How does Adipose tissue synthesize glycerol 3 phosphate
Glucose is broken down to dihyroxyacetone phosphate which is reduced to glycerol 3 phosphate
What is the activator of lipoprotein lipase?
Why cant adipose tissue synthesize TAG when insulin is slow?
insulin is needed for glucose uptake which is then converted to Glycerol 3 phosphate
What are the two enzymes that produces NADPH?
Glucose 6 phosphate dehydrogenase
Conversion of malate to pyruvate is done by what enzyme?
NADPH is produced
What enzyme converts pyruvate to OAA?
Addition of fatty acyl coA to glycerol 3 phosphate produces what?
Phosphatidic acid is converted to diacylglycerol by what enzyme?
What enzyme removes FA's from C1 and C3 of TAG's?
Hormone sensitive lipase (HSP)
What enzymes phosphorylate and thus induce the action of hormone sensitive lipase?
Glucagon, Epinephrine, Cortisol??, Thyroxine?, GH??
Glycerol released from TAG's cannot be used because?
Adipose tissue lacks glycerol kinase so it is instead transported to the liver
Upon hydrolysis from TAG's, how are FA activated?
By conversion to fatty acyl coA
What is the rate limiting enzyme of FA beta oxidation?
Fatty acyl coA enzyme that activates FA? is located where?
Outer mitochondrial membrane
Carnitine acyltransferase converts fatty acylcoA to what product?
Fatty acyl carnitine
Carnitine acyltransferase I (CPT I) is located where?
in the outer mitochondrial membrane
What happens to fattyacyl carnintine that is formed in the intermembranous space?
It is translocated into the mitochondrial matrix
What enzyme converts fattyacylcarnitine to fatty acyl coA in the mitochondrial matrix?
Carnitine acyltransferase II
What happens to the carnitine that is released in the mitochondrial matrix from the enzymatic action of Carnitine acyltransferase?
it is translocated back to the intermembraneous space
What are the sources of carnitine?
What chain length fatty acids need carnitine for transport into the mitochondrial matrix?
CAT I deficiency primarily affects what organ?
CAT II deficiency primarily affects what organs?
skeletal muscle and cardiac muscle
Medium chain acyl coA dyhydrogenase (MCAD) deficiency is a deficiency of what enzyme?
acyl coA dehydrogenase
What kind of FA's provide a glucogenic intermediate?
Odd chain Fatty acids
Why does only Odd chain fatty acids provide a glucogenic intermediate?
Because after beta oxidation, a 3 carbon molecule(propionyl coA) remains which is converted to succinyl coA
Methylmalonyl coA Mutase is involved in the conversion of priopionyl CoA to succinyl coA. What is the necessary coenzyme?
Vitamin B12 is needed for what processes?
myelination, RBC maturation, oxidation of Odd length chain fatty acids
What are the products of one round of beta oxidation on a FA?
Methylmalonic acidemia and aciduria can be caused by what factors, what are they?
Vit B12 deficiency
Methylmalonyl coA mutase
Which one is glucogenic, propionyl coA or acetyl coA?
Oxidation of unsaturated FA may require what high energy molecule?
Failure to target VLCFA to peroxisome or peroxisome insufficiency results in what syndrome?
Failure to transport VLCFA to Peroxisome results in what disorder?
What high energy molecule is used in beta oxidation in peroxisomes which produces the hydrogen peroxide radical?
Refsum's disease results from deficiency of what enzyme?
What are the 3 ketone bodies?
Ketone body production occurs where?
in the liver
Under what condition does ketone body formation occurs?
high TAG in the blood
Why are ketone bodies produced?
oxaloacetate is shunted to gluconeogenesis
acetyl coA cant form citrate with OAA
acetyl coA is diverted to form ketone bodies
Ketone bodies are made from what?
How are HMG coA made?
acetyl coA+ acetyl coA= acetoacetyl coA
acetoacetyl coA + acetyl coA= HMG coA
Which ketone body is not metabolized?
What gives rise to acetoacetate?
What is hypoketotic hypoglycemia?
low levels of ketone bodies and hypoglycemia
Which ketone body is readily usable?
Excretion of ketone bodies in urine causes what condition?
What activates LCAT?
Ammonia is converted to what?
In what situations is positive nitrogen balance?
When is negative nitrogen balance seen?
What types of protein are stable?
structural proteins (e.g)--Hb, collagen
HB 27 marker on MHC predisposes individuals to what condition?
Ankylosing spondylitis or other inflammatory conditions
Cholesystokinin and secretin are secreted in response to what in the stomach?
Zymogens are released to prevent what?
Why is digestion not normal in cystic fibrosis?
hepatopancreatic duct is clogged up with thick secretions so no enzymes reach the intestine--poor digestion
severe muscle wasting
What converts pepsinogen to pepsin?
H + in the stomach
What converts trypsinogen to trypsin?
What are serine proteases?
protein digesting enzymes
Trypsin cleaves what a.a?
Chemotrypsin cleaves what?
hydrophobic or acidic AA
Elastase cleaves what?
A.A with small side chains
ala, gly. ser
What are the 3 exopeptidases
Carboxypeptidase A, B
How is the transport of A.A differ across the luminal and serosal surface?
lumen-- Na+ cotransport ATP used
serosa-- facilitated diffusion
Deficiency of neutral amino acids transport causes?
Cystinuria or dibasic aciduria is caused by a deficiency of what a.a?
cystine, ornithine, lysine, Arginine
Dicarboxylic aciduria is caused by a deficiency of what a.a?
Joseph's syndrome or glycinuria is caused by?
gly, pro, hyprolinen
Hartnup has what conditions?
Cystinuria occurs bc of faulty transport of a.a where?
epithelia brush border of sm. intestine and renal tubules
Excess cysteine in blood can lead to ?
In a transamination, what new a.a is formed?
During starvation, glutamate is converted to what?
alpha keto glutarate
Peroxisomes have what amino acid oxidase?
L-amino acid oxidase
source of hydrogen peroxide
D-amino acid oxidase is used to degrade proteins from what source?
During Transamination, all nitrogen is tunneled into what a.a?
Alpha amino group is moved from what to what?
donor amino acid to an acceptor alpha keto acid
What vitamin is needed for transamination?
pyridoxal phosphate B6
Aminotransferases exist for all amino acids except what?
Apartate amino transferase and alanine aminotransferase are clinically important, why?
Indicates hepatic disease
What enzymes would be present in hepatic cell injury?
Gamma glutymal transferase
alcoholic liver cirhosis
Cholestatic lesion is caused by?
bile duct obstruction
Alkaline phosphatase is a marker for what two conditions?
Non-oxidative deamination is seen in what two a.a deamination?
Glutamate dehydrogenase utilizes what two high energy carriers?
Glutamate dehydrogenase converts glutamtate to what ?
alpha ketoglutarate and ammonium ion
Xanthine oxidase produces what?
Urea cycle takes place where?
The nitrogen atoms in urea come from what 2 sources?
The Carbon in urea comes from ?
Carbamoyl Phosphate I is involved in what cycle?
What is the rate limiting step of the urea cycle?
Carbamoyl Phosphate synthetase I
Formation of ornithine takes place where in the cell?
After citrulline is formed in the mitochondria what happens to it?
it enters the cytoplasm
What is the allosteric activator of Carbamoyl phosphate synthetase I?
How is nitrogen amount in the blood measured?
amount of nitrogen divided by the blood's urea (e.g.......14/60)
What is used to screen for kidney function?
BUN and creatine
Copper accumulation in the liver
causes chorea form movements
caudate deposition of copper
Kwashiokor condition results from protein deficient MEAL?
What does the MEAL stand for
Liver change (fatty) decreases lipoprotein synthesis
What converts pepsinogen to pepsin?
What converts Trypsinogen to trypsin?
Deficiency of absorption of neutral a.a like tryptophan results in what condition?
Which a.a are not absorbed in the PCT of the kidney and as a result cause Cystynuria?
What a.a is present in excess in the kidney in Cystynuria?
Absorption deficiency of cysteine in Cystynuria can cause what?
Defective neutral a.a transporter on kidney tubules and intestinal cells causes what condition?
Which a.a undergo non-oxidative deamination?
Upon deamination, aspartate becomes what?
Aminotransferases exist for all amino acids except 2, what are they?
In a transamination reaction,what does
alpha ketoglutarate become?
alpha ketoglutarate----> glutamate
Transaminases use what cofactor?
pyridoxal phosphate (Vitamin B6)
In a transamination rxn, what does
alpha ketoglutarate---> glutamate
What a.a give rise to alpha keto glutarate?
Urinary levels of FIGLu would be high bc of a deficiency of what?
What a.a give rise to pyruvate?
Phenylalanine hydroxylase uses what coenzyme?
Sources of succinyl coa
Isoleucine and valine
What accounts for the high mitochondrial mutation rate?
No proof reading capabilities
Any gene located in nucleus produces what pattern?
Identical mitochondria population
An example for reduced penetrance
Split hand deformity
Example of variable expression
mitochondrial mutations primarily produce what clinical disease?
Pearson syndrome affects what type of tissues?
tissue that depend on oxidative phosphorylation
What two coenzymes are needed for SAM regeneration?
What is the most soluble porphyrin?
Which porphyrin is not important for synthesis of heme?
Porphyrin I is elevated in what condition?
Heme containing proteins is called what?
Heme proteins are also present where?
All porphyrins have a characteristic absorption spectrum in what?
visible and ultraviolet light
400-700 nm is what light?
What is cancer phototherapy?
tumor take up porphyrin
tissue is irradiated with UV light bc porphyrin absorb UV
Biosynthesis of Heme?
Liver and bone marrow
Heme synthesis occurs where in the cell?
What are 3 processes that take place in mitochondria and cytosol?
What are the precursors of heme?
How many molecules of glycine and succinyl coA are needed for 1 molecule of heme?
What TCA cycle intermediate is used for heme synthesis?
how many molecules of acetyl coa are needed to form cholesterol?
What is the rate determining step of heme synthesis?
What coenzyme is needed for ala synthase
2 molecules of alpha alanine combine to form what?
What enzyme forms porphobilinogen?
1 porphobilinogen + 3 porphobilinogens coupling is catalyzed by what enzyme?
uroporphyrinogen I synthase
What converts hydroxymethylbilane to uroporphyrinogen II?
Uroporphyrinogen II synthase
Uroporphyrin is made from what?
What inhibits ALA synthase?
ALAS1 ia present where?
ALAS2 is present where?
At what molecular level does heme control the ALAS1 enzyme?
What is hemin?
oxidized (ferric) form of heme
Hemin is found where?
methemoglobin---> chocolate cyanosis
What sugar inhibts heme synthesis?
Drugs have what effect on ALA synthase?
they upregulate ALA synthase
Why would drugs upregulate ALA synthase?
cytochrome 450 uses heme and is involved in drug metabolism
Lead inhibits what 2 enzymes?
Lead poisoning causes what?
Porphyrias are caused by?
low heme presence
All but one porphyrias are inherited in what manner?
Porphyrias could be of 2 kinds?
What are they?
Acute type of porhyria is characterized by what?
What are the symptoms of cutaneous type of porphyria?
Acute intermittent porphyria
Uroporphobilinogen I synthase
Congenital erythropoietic Porphyria is caused by what?
uroporphobilinogen III synthase
Uroporphyrin I is found in what type of porphyria?
Congenital erythropoietic porphyria
Protophyria caused by a deficiency of what enzyme?
What diminshes photosensitivity?
X linked sideroblastic anemia is caused by what?
Deficiency of ALA synthase 2
What accumulates in Refsum disease?
phytanic acid---branched chain FA
What is the defect in Wilson disease?
Kayser-Fleisher ring is seen in what condition?
Treatment for Wilsons desease
Cause for Menke's Syndrome
Efflux of copper
What 2 acids undergo non oxidative deamination?
What two a.a do not have transaminases?
Oxidative deamination is catalyzed by what enzyme?
D amino acid oxidase uses what high energy coenzyme?
What are the 2 ways of transporting ammonia?
alanine from pyruvate
Amino acid oxidases rxn take place where in the cell?
Glutamate dehydrogenase (oxidative deamination) takes place where in the cell?
Formation of alanine from pyruvate is done by what enzyme?
The 2 nitrogens and 1 carbon in urea come from where?
N-aspartate via glutamate
N--free ammonium ion
How many ATP's are used in Urea cycle?
Argininosuccimic acidemia is caused by a deficiency of what enzyme?
What substrate accumulates in Fructose intolerance?
Fructose intolerance is caused by deficiency of what enzyme?
Essential fructosuria is caused by a deficiency of what enzyme?
Classic galactosemia is caused by what?
galactose 1 phosphate uridyltransferase
Glucose 6 phosphatase is found where in the cytosol?
ER in the liver
2 Uncoupling agents?
Accumulation of fructose 1 phosphate inhibits what pathway?
High levels of galactose and/or fructose result in what condition?
change to galacticol and fructisol
which are osmotically active
High levels of ammonium ion have what effect on the TCA cycle?
it depletes alpha ketoglutarate inhibiting TCA cycle
What is the only phospholipid with antigenic properties?
Plasmalogens are found where?
Cardiolipin is found where?
Inner mitochondrial membrane
Sphingomyelin has what backbone?
Which glycosphingolipids are common in membranes?
Paroxysmal Nocturnal Hemoglobinuria is caused by?
PIGA gene which is needed for synthesis of GIP anchors
What is a symptom of Paroxysmal Nocturnal Hemoglobinuria?
What phospholipid is deficient in Paroxysmal Nocturnal Hemoglobinuria?
What are the 3 types of Glycosphingolipids?
Globosides- N acetyl galactosamine
What degrades Phospholipids?
Glycerophospholipids are synthesized from where?
Glycerol 3 phosphate
Phosphatidylinositol is broken down into what two components?
IP3 and DAG
Digestion of lipids begins where?
Using what enzyme?
What are two enzymes that degrade short to medium chain fatty acids?
Where do they act?
What is the structure of bile salts?
sterol ring with taurine or glycine attached to it
Increasing chain unsaturation does what to melting point?
it decreases it
Which FA is needed for prostoglandin synthesis if arachidonic acid is not present?
The R1, R2, R3 is what in a TAG?
Human milk is rich in what TAGs?
Short and medium length fatty acids
Pancreatic lipase converts TAG's to what?
2 free fatty acids
What activates Lipase?
What does orlistat do?
inhibits pancreatic lipase secretion
C2 FA of phosphotidylcholine is removed by what enzyme?
What hormone stimulates the contraction of gall bladder?
Release of pancreatic enzyme?
Inhibits gastric emptying?
Which FA do not need miscelles for transport across SI Wall?
short and medium chain
Where in the enterocytes are TAG resynthesizes?
How are TAG resynthesized?
FA are activated by thiokinase and added to 2-monoglycerol
After cholesterol and FA are resynthesized in the ER what happens to them?
they are packed into a chylomicron with apo B48
Type I hypercholesterolemia is caused by what?
deficiency of Lipoprotein lipase or its activator apo protein C II
What leads to Familial Hyperlipoproteinemia type III?
deficiency of uptake of chylomicrons remnants
What a.a is used to form N-glycosidic bonds in glycoproteins?
FIGLu excretion in urine is a symptom of deficiency of what coenzyme?
What acts as a high energy reserve molecule in the muscle?
Non ketotic HyperGlycynemia is caused by what?
deficient glycine degradation
high glycine in blood
Deficiency of what enzyme causes non ketotic Hyperglycenemia?
Glycine cleavage complex
Primary Hyperoxaluria caused by?
increased conversion of glycine to oxalate
Glycinuria is caused by?
defective absorption of glycine in kidney
Biliverdin thats bound to albumin dissociates from albumin in the liver and binds to what?
What is needed for the conversion of heme to biliverdin?
NADPH, O2 and Fe
Biliverdin formation takes place where in the cell?
Salicylates and sulfanamides have what effect on the albumin-bilirubin complex?
it dissociates it, freezing bilirubin which can cross BBB and cause kernicterus
What is the rate limiting step in bilirubin excretion?
What does MOAT do?
Transports bilirubin into canaliculi
What drug increases the synthesis of UDP-Glucoronyl transferase?
What is Gilberts syndrome?
Partially deficient UDP glucuronyl transferase enzyme
deficient uptake of bilirubin
Deficient UDP glucuronyl transferase
Dubin Johnson and Rotor syndrome are what?
deficient excretion of conjugated bile
Alkaline phosphatase is a marker of what two physiological sites?
What is the direct reacting bilirubin?
What is the indirect reacting Bilirubin?
Which drug has combined effects of pharmokinetics and dynamics?