Biochem Flashcards
Histones are rich in what two amino acids?
Lysine and argenine (makes them positively charged)
Which is the only histone not found in the nucleosome core?
H1
Which histones make up the nucleosome core?
H2A, H2B, H3, H4 (each x2)
How does histone methylation affect gene transcription?
Methylation represses DNA transcription
“Methylation Mutes DNA”
How does Histone Acetylation affect gene transcription?
“Acetylation Activates DNA”
Relaxes DNA coiling, allowing for transcription
How does Leflunomide inhibit Pyrimidine base synthesis?
Inhibition of Dihydroorotate DH, which is responsible for the conversion of Carbamoyl phosphate into Orotic acid
How does Hydroxyurea inhibit pyrimidine base synthesis?
Inhibition of Ribonucleotide reductase, which is responsible for the conversion of UDP into dUDP
How does Methotrexate inhibit pyrimidine synthesis?
Inhibition of Dihydrofolate Reductase, which reduces DHF into THF
How does Trimethoprim (TMP) inhibit pyrimidine synthesis?
Inhibition of Dihydrofolate Reductase, which reduces DHF into THF
How does Pyrimethamine inhibit pyrimidine synthesis?
Inhibition of Dihydrofolate Reductase, which reduces DHF into THF
How does 5-Flourouracil (5-FU) inhibit pyrimidine synthesis?
Inhibition of Thymidylate sythase, which converts dUMP into dTMP
What is the RLS for pyrimidine synthesis?
Carbamoyl phosphate synthetase II
What is the precursor for 6-Mercaptopurine?
Azathioprine
What does 6-MP inhibit?
Purine base synthesis (PRPP–>IMP)
How does Mycophenolate inhibit purine base synthesis?
Inhibition of IMP DH
How does Ribavirin inhibit purine synthesis?
Inhibition of IMP DH
Deamination of which base gives uracil?
Cytosine
Why would a molecule with greater GC:AT ratio have a higher melting point?
G&C connect with 3 H bonds, A&T connect with 2 H bonds
What 5 substances are required to make a purine?
Glycine, Aspartate, Glutamine (GAG)
Tetrahydrofolate, CO2
What substances are required to make a pyrimidine?
Aspartate, Carbamoyl phosphate (glutamine+ATP+CO2)
Ribonucleotide reductase is an enzyme involved in the synthesis of what? What drug inhibits it?
Pyrimidine synthesis, Hydroxyurea
Thymidylate synthase is an enzyme involved in the synthesis of what? What drug inhibits it?
Pyrimidine synthesis, 5-FU
Dihydrofolate reductase is an enzyme used for the synthesis of what? What drugs inhibit it?
Pyrimidine synthesis; Methotrexate, Trimethoprim, Pyrimethamine
Orotic aciduria is caused by a mutation in what enzyme?
Pt has high orotic acid and ammonium levels
UMP synthase
Which GLUT receptors require insulin for glucose uptake and where are they found?
GLUT-4
-Skeletal muscle, Adipose tissue
Which GLUT transporter is responsible for fructose uptake in the GI tract?
GLUT-5
RLS of Glycolysis
PFK-1
RLS of Gluconeogenesis
Fructose 1,6 bisphosphate
RLS of TCA cycle
Isocitrate DH
RLS of Glycogenesis
Gycogen synthase
RLS of Glycogenolysis
Glycogen phosphorylase
RLS of HMP shunt
Glucose-6-phosphate DH (G6PD)
RLS of de novo Pyrimidine synthesis
Carbamoyl Phosphate Synthetase II
RLS of De novo Purine synthesis
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
RLS of Urea cycle
Carbamoyl Phosphate Synthetase I
RLS of fatty acid synthesis
Acetyl-CoA carboxylase (ACC)
RLS of fatty acid oxidation?
Carnitine acyltransferase I
RLS of Ketogenesis
HMG-CoA synthase
RLS of Cholesterol synthesis
HMG-CoA reductase
Pt with painful muscle cramps, myoglobinuria (red urine) with strenuous exercise and arrhythmia from electrolyte abnormalities
McArdle Dz (glycogen storage dz type V)
- Deficiency of Glycogen phosphorylase in muscle cells
- Can’t break down glycogen’s alpha 1,4 bonds
What enzyme is deficient in McArdle dz?
Glycogen phosphorylase (breaks down alpha 1,4 bonds)
Severe fasting hypoglycemia, elevated lactate in blood, hepatomegaly. Liver biopsy shows elevated glycogen in the liver cells
Von Gierke dz (glycogen storage dz Type I)
-Deficiency in Glucose-6-phosphatase (G6P=>glucose)
What is the enzyme deficient in Von Gierke dz?
Glucose-6-phosphatase
Milder form of type I glycogen storage dz with normal lactate
Cori dz (Type III) -lack of debranching enzyme (alpha1-6 bonds)
Glycogen storage dz leading to cardiomyopathy and early death
Pompe dz (type II) -Lack of lysosomal alpha-1-4-glucosidase
RLS of glycogen synthesis?
Glycogen synthase
RLS for glycogenolysis?
Glycogen phophorylase
What enzyme converts glucose-6-phosphate to glucose?
Glucose-6 phosphatase
Glycogen phosphorylase deficiency
McArdle dz
Glucose-6-phosphatase deficiency
Von Gierke dz
Lactic acidosis, hyperlipidemia, hyperuricemia (gout)
Von Gierke dz
Alpha 1,6 glucosidase deficiency (debranching enzyme)
Cori dz
Alpha 1,4 glucosidase deficiency
Pompe dz
Cardiomegaly
Pompe dz (infantile)
Diaphragm weakness leading to respiratory failure
Pompe dz (adult)
Increased glycogen in liver, severe fasting hypoglycemia
Von Gierke dz
Hepatomegaly, hypoglycemia, hyperlipidemia (normal kidneys, lactate and uric acid)
Cori dz
Painful muscle cramps, myoglobinuria with strenuous exercise
McArdle dz
Severe hepatosplenomegaly, enlarged kidneys
Von Gierke dz
What’s the RLS of the HMP shunt (pentose-phosphate) pathway?
Glucose-6-phosphate Dehydrogenase (G6PD)
What is G6PD usually used for?
Generation of NADPH
How does a deficiency of G6PD result in hemolytic anemia?
G6PD generates NADPH which is used by Glutathione Reductase to reduce Glutathione (GSH). Glutathione is used by Glutathione peroxidase to detoxify free radicals and peroxides.
Without G6PD, RBC are highly susceptible to oxidative damage and will lyse in response to oxidative stress
What enzyme is deficient in classic galactosemia?
Galactose-1P Uridyltransferase
-failure to thrive, cataracts, hepatomegaly, jaundice, mental retardation
Deficiency of Galactokinase
Galactokinase deficiency (feygit)
Deficiency of Aldolase B
Fructose intolerance
Deficiency of lactase
Lactose intolerance
Deficiency of Galactose-1P Uridyltransferase deficiency
Classic Galactosemia
Deficiency of Fructokinase
Essential fructosuria
What is Apo B-48 used for?
Chylomicron secretion from enterocyte to lymphatic system
What is Apo B-100 used for?
Liver packages VLDL with Apo B-100 for excretion into system (so cells can pull FFA off of it)
-Apo B-100 found on VLDL, IDL, LDL
What is the purpose of Apo E?
Mediates extra remnant uptake
What’s the purpose of Apo A-1?
Found on HDL, Activates LCAT (puts cholesterol from tissue cells onto HDL)
What’s the purpose of Apo C-II?
Cofactor for Lipoprotein lipase (LPL)
-LPL pulls FFA off of chylomicrons and VLDL and puts it into tissue
What is the RLS for cholesterol synthesis?
HMG-CoA reductase
What is cholesterol made from in the liver?
Acetyl-CoA
What is the RLS for Ketone synthesis?
HMG-CoA Synthase
What is the RLS for Fatty acid synthesis?
Acetyl-CoA Carboxylase
-FA synthesis occurs in the cytoplasm
What is the RLS for FA degradation?
Carnitine acyltransferase-1 (carnitine palmitoyl transferase 1)
What deficiency causes familial hypercholesterolemia?
LDL receptor deficiency
Activates LCAT
Apo A1
Mediates Chylomicron secretion
Apo B48
Binds to LDL receptor
Apo B100
Cofactor for lipoprotein lipase
Apo CII
Mediates uptake of remnant particles
Apo E
Mediates VLDL secretion
Apo B100
What are the essential amino acids?
"PVT TIM HaLL" Phenylalanine Valine Threonine Tryptophan Isoleucine Methionine Histidine Leucine Lysine
Classic basic AAs
Lysine, argenine (both have an extra ammonia group)
Histidine
Which of the basic AAs are found in high concentrations in histones?
Argenine and Lysine
-Their positive charges allow for interaction with (-) DNA
Acidic AAs
Aspartate, Glutamate (Aspartic acid, glutamic acid)
(-) charge at body pH
What’s the AA precursor for Epinephrine?
Phe=>Tyrosine=>DOPA=>Dopamine=>NE=>Epi
What amino acids build up in Maple Syrup urine dz?
"I LoVe maple syrup" Isoleucine Leucine Valine (Branched chain AAs)
What enzyme is deficient in Maple syrup urine dz?
alpha Ketoacid DH
