Biochemistry Flashcards
Adenosine deaminase deficiency is one of the major causes of what disease process?
SCID
What is the pathophysiology of Lesch-Nyhan syndrome?
Defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production and de novo purine synthesis.
What is the inheritance pattern of Lesch-Nyhan?
X linked recessive.
What are the clinical findings of Lesch-Nyhan?
Intellectual disability, self-mutilation, aggression, hyperuricemia, gout, dystonia. “HGPRT: Hyperuricemia, Gout, Pissed off, Retardation, dysTonia”
What is the treatment for Lesch-Nyhan?
Allopurinol or febuxostat (2nd line)
Which two disease involve the purine salvage pathway?
SCID and Lesch-Nyhan
What is the role of primase in DNA replication?
Makes an RNA primer on which DNA Pol III can initiate replication.
What is the function of DNA Pol III (prokaryotic only)?
Elongates strands
What is the function of DNA Pol I (prokaryotic only)?
Degrades RNA primer; replaces it with DNA
What is the function of telomerases?
An RNA-dependent DNA polymerase that adds DNA to the 3’ end of chromosomes to avoid loss of genetic material with every duplication.
What is a Missense DNA mutation?
Nucleotide substitution resulting in changed AA
What is a Nonsense DNA mutation?
Nucleotide substitution resulting in early stop codon
Nucleotide excision repair is defective in what disease?
Xeroderma pigmentosum; prevents repair of pyrimidine dimers because of UV exposure
Mismatch DNA repair is defective in which disease?
Hereditary Nonpolyposis Colorectal cancer (HNPCC)
Nonhomologous end joining DNA repair is mutated in which disease?
Ataxia telangiectasia
What are the 3 mRNA stop codons?
UGA, UAA, UAG
What toxin inhibits RNA pol II?
alpha-amantin; found in AManita phalloides (death cap mushroom)
What is the polyadenylation signal?
AAUAAA
Antibodies to spliceosomal snRNPs (anti-Smith Abs) are highly specific for what disease?
SLE
Anti-U1 RNP Abs are highly associated with what disease?
Mixed connective tissue disease
What is the purpose of snRNPs?
Small nuclear ribonucleoproteins; combine with primary transcripts to form spliceosome
Amino acids are bound to which end of the tRNA?
The 3’ end, attached to CCA
Which enzyme is responsible for attaching the correct amino acid to the tRNA?
Aminoacyl-tRNA synthetase
What are the eukaryotic ribosomal subunits?
40S + 60S –> 80S
Describe the process of translation elongation, including specific sites on the ribosome.
First, aminoacyl-tRNA binds to the A site. Then, rRNA catalyzes peptide bond formation, transfers growing polypeptide to amino acid in the A site. Ribosome advances 3 nucleotides toward the 3’ end of the mRNA, moving peptidyl tRNA to the P site (translocation).
Describe the steps of post-translational modification.
Removal of N- or C-terminal propeptides from zymogen to generate mature proteins (e.g., trypsinogen to trypsin). Phosphorylation, glycosylation, hydroxylation, methylation, acetylation, and ubiquitination.
p53 and Rb normally inhibit which transition in the cell cycle?
G1 to S progression
What are examples of “permenent” cell types? (Cells that remain in G0 and are regenerated from stem cells)
Neurons, skeletal and cardiac muscle, RBCs
What are examples of “stable/quiescent” cell types? (Cells that enter G1 from G0 when stimulated)
Hepatocytes, lymphocytes
What are examples of “labile” cell types? (Cells that never go to G0, divide rapidly with a short G1, most affected by chemotherapy)
Bone marrow, gut epithelium, skin, hair, germ cells
What are Nissl bodies?
Rough ER in neurons - synthesize peptide neurotransmitters for secretion
What is inclusion cell disease (I-cell disease)?
Inherited lysosomal storage disorder; defect in phosphotransferase. Failure of Golgi to phosphorylate mannose residues on glycoproteins. Proteins are secreted extracellularly rather than delivered to lysososomes.
What are the clinical features of I-cell disease?
Course facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Often fatal in childhood.
What is Signal Recognition Protein (SRP) responsible for?
Trafficking proteins from ribosome to RER
COPI (a vesicular trafficking protein) moves vesicles from where to where?
Golgi –> Golgi (retrograde); Golgi –> ER
COPII (a vesicular trafficking protein) moves vesicles from where to where?
Golgi –> Golgi (anterograde); ER –> Golgi
Clathrin (a vesicular trafficking protein) moves vesicles from where to where?
trans-Golgi –> lysosomes; plasma membrane –> endosomes
What is a peroxisome?
Membrane-enclosed organelle involved in catabolism of very long-chain fatty acids, branched-chain fatty acids, and amino acids
What is a proteasome?
Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.
Microtubules compose which 3 cellular structures?
Flagella, cilia, and mitotic spindles (& more)
Describe Kartagener syndrome?
Immotile cilia due to a dynein arm defect. Resuls in male and female infertility, can cause bronchiectasis, recurrent sinusitis, and situs inversus.
What is the most abundant protein in the human body?
Collagen
Type I collagen composes what?
Bone, skin, tendon, dentin, fascia, cornea, late wound repair
Type II collagen composes what?
Cartilage, vitreous body, nucleus pulposus ; “carTWOlage”
Type III collagen composes what?
Reticulin-skin, blood vessels, uterus, fetal tissue, granulation tissue
Type IV collagen composes what?
Basement membrane, basal lamina, lens
Which vitamin is required for collagen synthesis?
VitC (scurvy Arrrrrrrrgh). The arrrrghh is for pirates, by the way.
Problems in forming the triple helix of collagen results in what disease?
Osteogenesis imperfecta
Problems with cross-linking staggered tropocollagen molecules outside fibroblasts results in what disease?
Ehlers-Danlos
What is the inheritance pattern of the most common form of osteogenesis imperfecta? What type of collagen is defected?
Autosomal dominant; Type 1 collagen
What are the clinical manifestations of Osteogenesis imperfecta?
Brittle bones, blue sclerae, hearing loss, dental imperfections
What are the clinical manifestations of Ehlers-Danlos?
Hyperextensible skin, tendency to bleed, and hypermobile joints
What are the three types of Ehlers-Danlos?
Hypermobility type (most common), Classical type (joint/skin), and Vascular type (type III collagen)
What is the pathophysiology of Menkes disease?
Connective tissue disease caused by impaired copper absorption and transport. Less activity of lysyl oxidase.
What are the clinical manifestations of Menkes disease?
Brittle kinky hair, growth retardation, and hypotonia
Elastin is broken down by elastase. Which molecule normally inhibits elastase? (The deficiency of this can lead to emphysema)
alpha1-antitrypsin
Marfan syndrome is caused by a defect in what?
Fibrillin, which forms a sheath around elastin
What does PCR amplify?
A piece of DNA
What are the steps of PCR?
- Denaturation of DNA by heating
- Annealing - during cooling, excess premade DNA primers anneal to specific sequence on each strand to be amplified
- Elongation - heat stable DNA polymerase replicates DNA
* steps are repeated multiple times
What is used to compare the size of separate PCR particles?
Agarose gel
What is Southern blot used for?
Visualize DNA particles
What is Northern blot used for?
Visualize RNA particles
What is Western blot used for?
Sample protein is separated via gel electrophoresis and transferred to a filter. Labeled Ab used to bind to relavant protein.
What is Southernwestern blot used for?
Identify DNA-binding proteins using labeled oligonucleotide probes
What are microarrays used for?
Used to profile gene expression levels of thousands of genes simultaneously to study certain diseases and treatments. Able to detect single nucleotide polymorphisms and copy number variations.
What is an indirect ELISA?
Uses a test antigen and a labeled Ab to detect another Ab in patient’s serum (HIV ELISA works this way)
What is a direct ELISA?
Uses a test Ab to see if specific antigen is present in patient’s blood. A secondary Ab coupled to an enzyme is added to detect the antigen.
What is the approximate sensitivity and specificity of ELISA tests?
100%
What are FISH studies used for?
Used for specific localization of genes and direct visualization of anomalies at molecular level; fluorescence - gene is present, no fluorescence - gene has been deleted
What is Cre-lox system?
Can inducibly manipulate genes at specific developmental points (to study a gene whose deletion causes embryonic death)
What is RNA interference (RNAi)
A dsRNA is synthesized that is complementary to an mRNA of interest. When inserted into human cells, the dsRNA splits and promotes degradation of target mRNA, “knocking down” expression.
In genetics, what is pleiotropy?
One gene contributes to multiple phenotypic effects
In genetics, what is locus heterogeneity?
Mutations at different loci can produce a similar phenotype
In genetics, what is allelic heterogeneity?
Different mutations in the same locus produce the same phenotype
In genetics, what is heteroplasmy?
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease
What is uniparental disomy?
Offspring receives 2 copies of a chromosome from 1 parent and no copies from other parent (correct number of total chromosomes) - this is NOT Down Syndrome.
Prader-Willi and Angelman syndromes are due to deletions of genes on which chromosome?
15
What is the inheritance pattern of Hypophosphatemic rickets?
X-linked dominant
Mitochondrial myopathies are a rare group of disorders that often present with what?
Myopathy, lactic acidosis, and CNS disease; secondary to failure in oxidative phosphorylation.
What does muscle biopsy of mitochondrial myopathies usually show and what stain is used?
“Ragged red fibers” on Gomori trichrome stain - yes, I got a World question on this :{
What are the names of the three classic Mitochondrial myopathies?
- Myoclonic epilepsy with ragged red fibers (MERRF)
- Leber optic neuropathy (blindness)
- Mitochondrial encephalopathy with stroke-like episodes and lactic acidosis (MELAS)
What disease is associated with defective Type IV collagen?
Alport syndrome
Multiple endocrine neoplasias (MEN) types 2A and 2B are associated with which gene?
Ret gene
NF type 1 is caused by mutations in the NF1 gene on which chromosome?
17
NF type 2 is caused by mutations in the NF2 gene on which chromosome?
22
What are the findings of NF type 2?
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas
CF is due to mutations in the CFTR gene on which chromosome?
7
What are the treatments of CF?
N-acetylcysteine to loosen mucus plugs, dornase alfa (DNAse) to clear leukocytic debris, enzymes for digestion
What are the classic X-linked recessive disorders?
“Be Wise, Fool’s GOLD Heeds Silly HOpe.” Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne (and becker) muscular dystrophy, Hunter Syndrome, Hemophilia A and B, Ornithine transcarbamylase deficiency
What is the specific type of mutation in Duchenne muscular dystrophy? In Becker?
Frameshift and point respectively
What is a common cause of death in patients with Duchenne?
Dilated cardiomyopathy
Describe Myotonic type 1 muscular dystrophy
CTG trinucleotide repeat expansion in the DMPK gene –> abnormal expression of myotonin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
Fragile X syndrome involves which gene?
FMR1
Fragile X syndrome is a trinucleotide repeat of what?
CGG
What are the findings of Fragile X syndrome?
Intellectual disability, macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse
Prenatal screening of a fetus with DS would show what?
Low AFP, high beta-hCG, low estriol, high inhibin A
What are the health risks of a person with DS?
Duodenal atresia, Hirschsprung disease, congenital heart disease (ASD - ostium primum), ALL, AML, Alzheimer
Prenatal screening of a fetus with Edwards would show what?
Low AFP, low beta-hCG, low estriol, low or normal inhibin A
Prenatal screening of a fetus with Patau would show what?
Low free beta-hCG, low PAPP-A, and high nuchal translucency
What is Cri-du-chat syndrome?
Congenital microdeletion of short arm of chromosome 5 (46,XX or XY, 5p-). Findings are microcephaly, moderate to severe intellectual disability, high-pitched crying, epicanthal folds, cardiac abnormalities (VSD)
What is Williams syndrome?
Congenital microdeletion of the long arm of chromosome 7 (includes elastin gene). Findings are distinctive “elfin” facies, intellectual disability, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, CV problems.
22q11 deletions lead to what in a developing fetus?
Aberrant development of the 3rd and 4th branchial pouches.
What are the findings of 22q11 syndromes?
Variable presentation including Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia; “CATCH-22”
What’s another name for VitB1?
Thiamine
What’s another name for VitB2?
Riboflavin, FAD
What’s another name for VitB3?
Niacin, NAD+
What’s another name for VitB5?
Pantothenic acid: CoA
What’s another name for VitB6?
Pyridoxine
What’s another name for VitB7?
Biotin
What’s another name for VitB9?
Folate
What’s another name for VitB12?
Cobalamin
What’s another name for VitC?
Ascorbic acid
What is the function of VitB1?
In thiamine pyrophosphate, a cofactor for several dehydrogenase enzyme reactions: Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase, branched-chain ketoacid dehydrogenase
What are the symptoms of deficiency of VitB1?
Deficiency: Impaired glucose breakdown which leads to -
Wenicke-Korsakoff syndrome (malnutrition and alcoholics), Dry beriberi, Wet beriberi
What is the function of VitB2?
Component of flavins FAD and FMN, cofactors in redox reactions
What are the symptoms of deficiency of VitB2?
Cheilosis and corneal vascularization
What is the function of VitB3?
Constituent of NAD+, NADP+ (redox reactions). Derived from tryptophan. Synthesis requires B2 and B6. Used to treat dyslipidema; lowers VLDL and raises HDL.
What are the symptoms of deficiency of VitB3? Of excess?
Deficiency: Glossitis, pellagra, malignant carcinoid syndrome can cause deficiency. Symptoms of pellagra include diarrhea, dementia, dermatitis
Excess: Facial flushing, hyperglycemia, hyperuricemia
What is the function of VitB5?
Essential component of coenzyme A and fatty acid synthase
What are the symptoms of deficiency of VitB5?
Deficiency: Dermatitis, enteritis, alopecia, adrenal insufficiency
What is the function of VitB6?
Converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation, glycogen phosphorylase. Synthesis of lots of neurotransmitters.
What are the symptoms of deficiency of VitB6?
Convulsions, hyperirritability, peripheral neuropathy, siderblastic anemias
What is the function of VitB7?
Cofactor for carboxylation enzymes
What are the symptoms of deficiency of VitB7?
Rare.. dermatitis, alopecia, enteritis
What is the function of VitB9?
Converted to THF, a coenzyme for 1C transfer/methylation reactions. Important in synthesis of bases in DNA and RNA.
What are the symptoms of deficiency of VitB9?
Neural tube defects, macrocytic megaloblastic anemia, hypersegmented PMNs, glossitis, no neuro symptoms
What is the function of VitB12?
Cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase.
ake hemoglobin.
What are the symptoms of deficiency of VitB12?
Macrocytic megaloblastic anemia, hypersegmented PMNs, paresthesias, subacute combined degeneration of spinal cord due to abnormal myelin
What is the function of VitC?
Antioxidant, facilitates iron absorption by reducing it to ferrous state. Necessary for hydroxylation of proline and lysine in collagen synthesis. Necessary for DA beta-hydroxylase, which converts DA–>NE.
What are the symptoms of deficiency of VitC? Of excess?
Deficiency: Scurvy, weakened immune response
Excess: Nausea, vomiting, diarrhea, fatigue, Ca oxalate nephrolithiasis.
What is the function of VitD? *And what are all its different names and forms (4 of them)
D2 = ergocalciferol - ingested from plants
D3 = cholecalciferol - consumed in milk, formed in sun-exposed skin (stratum basale)
25-OH D3 = storage form
1,25-(OH)2D3 (calcitriol) = active form
Increase intestinal absorption of Ca and phosphate, increase bone mineralization
What are the symptoms of deficiency of VitD? Of excess?
Deficiency: Rickets, osteomalacia, hypocalcemia tetany
Excess: Hypercalcemia, hypercalciuria, loss of appetite, stupor; seen in sarcoidosis
What is the function of VitE?
Antioxidant (protects erythrocytes and membranes from ROS)
What are the symptoms of deficiency of VitE?
Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination
What is the function of VitK?
Cofactor for the gamma-carboxylation of glutamic acid residues on various proteins required for blood clotting (II, VII, IX, X); synthesized by intestinal flora
What are the symptoms of deficiency of VitK?
Neonatal hemorrhage with inreased PT and aPTT but normal bleeding time
What is the function of Zinc?
Essential for activity of 100+ enzymes
What are the symptoms of deficiency of Zinc?
Delayed wound healing, hypogonadism, dysgeusia, anosmia, acrodermatitis enteropathica
What is the function of VitA?
Antioxidant, visual pigments, used to treat measles and AML subtype M3
What are the symptoms of deficiency of VitA? Of excess?
Deficiency: Night blindness (nyctalopia), dry scaly skin, alopecia, corneal degeneration, immune suppression
Excess: Arthralgias, skin changes, alopecia, cerebral edema, pseudotumor cerebri, osteoporosis, teratogenic
What are the general steps of ethanol metabolism?
Ethanol –> acetaldehyde (via alcohol dehydrogenase, in cytosol) –> acetate (via acetaldehyde dehydrogenase, in mitochondria)
What is the MOA of fomepizole and when is it used?
Inhibits alcohol dehydrogenase and is an antidote fro methanol or ethylene glycol poisoning
What is the MOA of disulfiram and when is it used?
Inhibits acetaldehyde dehydrogenase - acetaldehyde accumulates leading to hangover symptoms. Used to treat alcoholism. Aka Antabuse.
Where in the cell does glycolysis occur?
Cytoplasm
Where in the cell does fatty acid oxidation occur?
Mitochondria
Where in the cell does steroid synthesis occur?
Cytoplasm
Where in the cell does heme synthesis occur?
Both cytoplasm and mitochondrion
Where in the cell does oxidative phosphorylation occur?
Mitochondria
Where in the cell does cholesterol synthesis occur?
Cytoplasm
Where in the cell does HMP shunt occur?
Cytoplasm
Where in the cell does protein synthesis occur?
Cytoplasm
Where in the cell does acetyl-CoA production occur?
Mitochondria
Where in the cell does TCA cycle occur?
Mitochondria
Where in the cell does the urea cycle occur?
Both cytoplasm and mitochondrion
Where in the cell does gluconeogenesis occur?
Both cytoplasm and mitochondrion
Where in the cell does fatty acid synthesis occur?
Cytoplasm
What is the rate-determining step of glycolysis? And what are its regulators?
PFK-1
Stimulated by AMP, fructose-2,6-bisphosphate
Inhibited by ATP, citrate
What is the rate-determining step of gluconeogenesis? And what are its regulators?
Fructose-1,6-bisphosphatase
Stimulated by ATP, acetyl-CoA
Inhibited by AMP, fructose-2.6-bisphosphate
What is the rate-determining step of the TCA cycle? And what are its regulators?
Isocitrate dehydrogenase
Stimulated by ADP
Inhibited by ATP, NADH
What is the rate-determining step of glycogenesis? And what are its regulators?
Glycogen synthase
Stimulated by glucose-6-phosphate, insulin, cortisol
Inhibited by epinephrine, glucagon
What is the rate-determining step of glycogenolysis? And what are its regulators?
Glycogen phosphorylase
Stimulated by epinephrine, glucagon, AMP
Inhibited by glucose-6-phosphate, insulin, ATP
What is the rate-determining step of the HMP shunt? And what are its regulators?
G6PD
Stimulated by NADP+
Inhibited by NADPH
What is the rate-determining step of de novo pyrimidine synthesis? And what are its regulators?
Carbamoyl phosphate synthetase II
Stimulated by PRPP
Inhibited by UTP
What is the rate-determining step of de novo purine synthesis? And what are its regulators?
PRPP amidotransferase
Inhibited by AMP, inosine monophosphate (IMP), GMP
What is the rate-determining step of the urea cycle? And what are its regulators?
Carbamoyl phosphate synthetase I
Stimulated by N-acetylglutamate
What is the rate-determining step of fatty acid synthesis? And what are its regulators?
Acetyl-CoA carboxylase (ACC)
Stimulated by insulin, citrate
Inhibited by glucagon, palmitoyl-CoA
What is the rate-determining step of fatty acid oxidation? And what are its regulators?
Carnitine acyltransferase I
Inhibited by malonyl-CoA
What is the rate-determining step of ketogenesis?
HMG-CoA synthase
What is the rate-determining step of cholesterol synthesis? And what are its regulators?
HMG-CoA reductase
Stimulated by insulin, thyroxine
Inhibited by glucagon, cholesterol
What is the effect of arsenic poisoning?
Causes glycolysis to produce zero net ATP
What are the major differences between hexokinase and glucokinase?
Hexokinase: In most tissues, not very selective, low Km for sugars, inhibited by glucose-6-P, low Vmax
Glucokinase: In liver and pancreatic beta cells, selective for glucose, high Km, inhibited by fructose-6-P, high Vmax, induced by insulin
What is the net glycolysis reaction?
Glucose + 2ADP + 2Pi + 2NAD –> 2Pyruvate + 2ATP + 2NADH + 2H + 2H2O
As a general rule of thumb, does glucagon phosphorylate or dephosphorylate?
Phosphorylates
Pyruvate dehydrogenase links what reaction?
Pyruvate –> Acetyl-Co-A
What are the clinical findings of arsenic poisoning?
Vomiting, rice-water stools, garlic breath
What are the 5 cofactors required by pyruvate dehydrogenase complex?
Pyrophsophate (B1), FAD (B2), NAD (B3), CoA (B5), Lipoic acid
What are the clinical findings of pyruvate dehydrogenase deficiency?
Neuro defects, lactic acidosis, high serum alanine
What is the MOA of the toxin ricin?
Inhibits protein synthesis by cleaving the rRNA component of the 60S subunit
Anemia from lead poisoning is due to the inhibition of which two enzymes?
Ferrochelatase and delta-aminlevulinicacid (ALA) dehydratase
What are the two organs that can make and secrete glucose and why?
Liver and kidney; only two tissues with Glucose-6-Phosphatase, the final enzyme in gluconeogenesis
What does the Krebs cycle produce?
3NADH, 1 FADH2, 1 GTP, 10 ATP/Acetyl-CoA
What exactly does Rotenone block in the electron transport chain?
Complex I
What exactly does Anitmycin A block in the electron transport chain?
Complex III
What exactly do Cyanide and CO block in the electron transport chain?
Complex IV
What exactly does Oligomycin block in the electron transport chain?
Complex V (ATP synthase)
What is the purpose of the HMP shunt?
Provides a source of NADPH when glucose-6-P is abundant, yields ribose for nucleotide synthesis and glycolytic intermediates
What are the tissue sites of the HMP shunt?
Lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs
What is the rate-limiting step of the HMP shunt?
G6PD enzyme
What gives sputum its blue-green pigment?
Myeloperoxidase from activated macrophages and neutrophils
What is the purpose of the respiratory (oxidative) burst?
Involves activation of the phagocyte NADPH oxidase complex which utilizes oxygen to rapidly release ROS
How can patients with CGD produce ROS? What kind of organisms are they susceptible to?
They utilize H2O2 generated by invading organisms and convert it to ROS. They are susceptible to catalase positive organisms.
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
What is the pathophysiology of G6PD deficiency?
HMP shunt is ineffective, which means that NADPH cannot be regenerated. NADPH is important in detoxifying ROS and peroxidases. Low NADPH in RBCs leads to hemolytic anemia due to ROS damage.
In which step of glycolysis does fructose enter?
Glyceraldehyde-3-P
Which two enzymes convert fructose into glyceraldehyde-3-P?
Fructokinase and aldolase B
Essential fructosuria involves a defect in which enzyme? What is its inheritance pattern?
Fructokinase, aut recessive
What is the clinical presentation of essential fructosuria?
Benign and asymptomatic since fructose does not get trapped in cells. Presents with fructose in blood and urine.
Fructose intolerance involves a defect in which enzyme? What is its inheritance pattern?
Aldolase B, aut recessive
What is the clinical presentation of fructose intolerance?
Hypoglycemia, jaundice, cirrhosis, vomiting
What is the pathogenesis of fructose intolerance?
Fructose-1-P accumulates causing decreased available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
What is the treatment of fructose intolerance?
Decrease intake of both fructose and sucrose (glucose+fructose)
How does galactose enter glycolysis?
Galactose –> Galactose-1-P –> Glucose-1-P –> Glucose-6-P (glycolysis)
What is the inheritance pattern of galactokinse deficiency ?
Autosomal recessive
What is the pathogenesis of galactokinase deficiency?
Galactitol accumulates if galactose is present in diet. Relatively mild condition.
What is the clinical presentation of galactokinase deficiency?
Galactose in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.
Classic galactosemia involves a defect in which enzyme? What is its inheritance pattern?
Galactose-1-P uridyltransferase, autosomal recessive
What is the pathogenesis of classic galactosemia?
Galactitol et. al. accumulate in lens of eye
What is the clinical presentation of classic galactosemia?
Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
What is the treatment of classic galactosemia?
Exclude galactose and lactose (galactose+glucose) from diet
Classic galactosemia can lead to what infection in neonates?
E. coli sepsis
What is the role of P-bodies?
mRNA quality control centers in the cytoplasm of cells
What is the nucleotide sequence at the 3’ end of tRNAs?
CCA
Which end on tRNAs do amino acids bind to?
3’ -OH end
What is the purpose of the D loop of tRNAs?
Contains dihydrouridine residues which help facilitate correct tRNA recognition by proper aminoacyl tRNA synthetase
What is the purpose of the T loop of tRNAs?
Contains a sequence necessary for tRNA binding to ribosomes
To which end of the RNA is the poly-A tail added?
3’
To which end of the RNA is the methylguanosine cap added?
5’
Which enzyme converts glucose to its alcohol counterpart, sorbitol?
Aldose reductase
Some tissues convert sorbitol to fructose using what enzyme?
Sorbitol dehydrogenase
Which tissues have both aldose reductase (glucose–>sorbitol) and sorbitol dehydrogenase (sorbitol–>fructose)?
Liver, ovaries, and seminal vesicles
Which tissues have primarily aldose reductase (glucose–>sorbitol) and not sorbitol dehydrogenase (sorbitol–>fructose)?
Schwann cells, retina, kidneys, lens
Dietary lactose intolerance is due to deficiency of which enzyme?
Lactase
What are the aromatic amino acids?
Tryptophan, phenylalanine, tyrosine
What are the essential amino acids?
Methionine, valine, histidine, isoleucine, phenylalanine, threonine, tryptophan, leucine, lysine
What are the acidic amino acids?
Aspartic acid and glutamic acid
What are the basic amino acids?
Arginine, lysine, histidine
What are the sulfur-containing amino acids?
Methionine and cysteine
What are the branched amino acids?
Isoleucine, leucine, valine
What does it mean to be a ketogenic amino acid?
No glucose production. Breakdown gives acetyl-CoA.
What does it mean to be a glucogenic amino acid?
Produce pyruvate or Kreb cycle intermediates.
Serum methylmalonic acid levels would help in the diagnosis of what?
VitB12 deficiency
Erythrocyte glutathione reductase levels would help in the diagnosis of what?
VitB2 (riboflavin) deficiency
Thiamine deficiency decreases the activity of what enzymes?
Transketolase
Serum protoporphyrin levels are increased in what disease process?
Iron deficiency anemia
What are the findings in Patau syndrome?
Severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease
What are the findings in Edwards syndrome?
Severe intellectual disability, rocker-bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease
How are fatty acids covalently anchored to plasma membrane cysteine residues?
Palmitoylation - increases protein hydrophobicity by anchoring receptor carboxyl tails to plasma membrane
Describe the latex agglutination test
Used to detect for presence of an antigen in a sample of interest. Add sample to collection of specific antibodies fixed to latex beads.
What is the Kozak consensus sequence?
(gcc)gccRccAUGG; helps initiate 5’ cap-dependent translation in eukaryotes
What is the Shine-Dalgarno sequence?
AGGAGG; facilitates translation initiation in prokaryotes
What is an open reading frame?
A continuous stretch of codons that code for a polypeptide without an intervening stop codon. Eukaryotes usually have 1 in a single mRNA transcript whereas prokaryotes often have many
What is ‘internal ribosome entry?’
During apoptosis, eIF degrades leading to interruption of translation. But proteins necessary for apoptosis continue to be translated through internal ribosome entry. A distinct nucleotide sequence called the internal ribosome entry site (IRES) attracts eukaryotic ribosome to mRNA and allows translation to begin in the middle of the mRNA sequence.
Does DNA methylation activate or silence those genes?
Silences
The two nitrogens in urea come from where?
1 N from ammonia and 1 N from aspartate
What is the purpose of the urea cycle?
To convert toxic ammonia to urea which can be excreted by the kidney
Where does the urea cycle take place?
Liver
What is the treatment of hyperammonemia?
Limit protein in diet. Benzoate or phenylbutyrate bind amino acid and lead to excretion and may be given to decrease ammonia levels. Lactulose to acidify the GI tract and trap NH4+ for excretion.
What are the symptoms of ammonia intoxication?
Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurry vision
What is Carbamoyl phosphate synthetase I’s required cofactor?
N-acetylglutamate
What is the most common urea cycle disorder? What is its inheritance pattern?
Ornithine transcarbamylase deficiency; X-linked recessive
When does ornithine transcarbamylase deficiency usually present?
Usually evident in first first few days of life, but can present with late onset
What happens to the excess carbamoyl phosphate in ornithine transcarbamylase deficiency?
Converted to orotic acid (part of pyrimidine synthesis pathway)
What are the findings of ornithine transcarbamylase deficiency?
Increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs. orotic aciduria).
What are the derivatives of phenylalanine?
Phenylalanine (using BH4) –> Tyrosine (can diverge to make thyroxine) –> Dopa (can diverge to make melanin) –> Dopamine (using VtC) –> NE (using SAM) –> Epi
What are the derivatives of tryptophan?
Tryptophan (using B6) –> Niacin –> NAD+/NADP+
or
Tryptophan (using BH4 and B6) –> Serotonin –> Melatonin
What are the derivatives of histidine?
Histidine (using B6) –> Histamine
What are the derivatives of glycine?
Glycine (using B6) –> Porphyrin –> Heme
What are the derivatives of glutamate?
Glutamate (using B6) –> GABA
or
Glutamate –> Glutathione (GSH)
What are the derivatives of arginine?
Creatinine, urea, and nitric oxide
What are the derivatives of methionine?
Methionine –> SAM (high energy) –> SAH –> homocysteine –> cysteine or methionine
Alkaptonuria is a defect of what enzyme?
Homogentisate oxidase (tyrosine –> fumarate)
PKU (Phenylketonuria) is due to deficiency of what enzyme?
Phenylalanine hydroxylase
In PKU when phenylalanine cannot turn into tyrosine, what does it turn into instead?
Phenylpyruvate and phenylacetate (increased phenylketones in urine)
What are the clinical symptoms and findings of PKU?
Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor
What is the treatment of PKU?
Less phenylalanine and more tyrosine in diet
What is the inheritance pattern of PKU?
Autosomal recessive
What are the clinical findings of alkaptonuria?
Dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias.
What are the clinical findings of homocystinuria?
Increased homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, lens subluxation, thrombosis, and atherosclerosis
Describe the pathogenesis of cystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter for cysteine, ornithine, lysine, and arginine (COLA). May lead to precipitation of hexagonal cystine stones.
Where does synthesis of preprocollagen and procollagen take place?
RER
Where does transformation of procollagen to tropocollagen take place
Outside the fibroblast
Where does cross-linking of tropocollagen molecules take place?
Outside the fibroblast
Transamination requires which cofactor?
Pyridoxine (B6)
