Biochemistry Flashcards
(279 cards)
1
Q
What is the charge of DNA double helix?
A
Negative
2
Q
What is the charge of nucleosome?
A
Positive charge
3
Q
what are histones?
A
Amino acid lysine and arginine (Histones bind to nucleosomes and to linker DNA)
4
Q
what phase does DNA and histone synthesis occur?
A
During the S phase
5
Q
what are the characteristics of heterochromatin?
A
Condensed DNA, transcriptional inactive, and sterically inaccessible
6
Q
What is Euchromatin?
A
Less condesned,lighter on EM, and transcriptionally active
7
Q
What is DNA methylation?
A
Template strands (Cytosine and adenine) are methylated in DNA replication, so mismatch repair enzymes can distinguish between old and new strands.
8
Q
what happens in histone methylation?
A
usually suppresses DNA transcription, can can activate it in some cases
9
Q
what does histone ACETYLATION do?
A
Relaxes DNA coiling and allows for transcription
10
Q
What are the differences between nucloetides?
Nucloside
Nucleotide?
A
Nucloside: base + deoxyribose (sugar)
Nucleotide: base + deoxyribose +phosphate (linkare 3-5 phosphodiester bond)
11
Q
What is the difference between a purine and pyrimidine?
A
PURines (A, G) has 2 rings
Pyrimidines (C, U, T) 1 ring
12
Q
where is Uracil found?
Where is thymine found?
A
Uracil is RNA
Thymine is in DNA
13
Q
What determines the melting temperature of DNA?
A
Number of C-G bonds (3- H bonds so stronger) then A-T (2 H bonds)
14
Q
What amino acids are needed for purine synthesis?
A
GAG (gycine, aspartate, glutamine)
15
Q
What are medications that disrupt pyrimidine synthesis?
A
1) Leflunomide: dihydroorotate dehydroxygenase
2) Methrotrexate, trimethoprim (TMP), pyrimethamine (dihydrofolate reductase)
3) 5-flurocil: forms 5-F-dUMP inhibits thymidylate synthase
16
Q
What disrupts purine synthesis?
A
6-mercaptopurine and azathioprine: de novo purine synthesis
Mycophenolate and ribavirin: inhibits inosine monophospahte dehydrogenase
17
Q
What disrupts purine and pyrimidine synthesis?
A
Hydroxyurea: ribonucleotide reductase
18
Q
what are two medications that act on purine slavage pathways?
Which step do they act on?
A
1) Allopurinol and febuxostat, Probenecid
2) Allopurinol/febuxostat: Act on X0 (which is enzyme) prevents formation of Xanthine to Uric acid)
3) Probenecid: increases the transformation of Uric acid to urine
All these medications are used for gout
19
Q
what does adenosine deaminase deficiency cause?
A
1) SCID (severe combined immunodeficiency syndrome)
2) Increases dATP, which is toxic to lymphocytes.
20
Q
What is Lesch-Nyhan Syndrome?
What are the signs?
A
Deficiency in HGPRT enzyme
Symtoms match abbreviation (HyperuricemisGoutPissed off aggresionRetrardation DysTonia
21
Q
What are features of the genetic code?
A
1) Unambiguous: each codon is 1 amino acid
2) Degenerate/ redundant: most amino acids are coded by mutiple codons (except mehtionin and tryptophan)
3) Comaless/nonoverlapping: read from a fixed point, continuous sequence of bases (except virus)
4) Universal: genetic code is conserved throughout evolution, except in human mitochrondria.
22
Q
Where does origin of replication of DNA occur?
What is the difference between prokaryotes and eukaryotes promotor?
A
Base pairs, usually promoters (A-T rich segments)
2) Eukaryotes may have more then one promoter
23
Q
What is the replication fork?
A
Y shaped region where the leading and lagging strands are synthesized
24
Q
what is the function of helicase?
A
Unwinds the DNA at replication fork
25
What are the function of single stranded binding proteins?
Prevents strands from reannealing
26
What is function of DNA topoisomerase?
Create single or double stranded breaks in the helix to add or remove supercoils
27
What medications are DNA toposiomerase inhibitors?
fluroquinones
28
What is the function of primase?
Makes RNA primer on which DNA polymerase III can initiater replication
29
What is DNA polymerase III?
Prokaryote only, elongates the leading strand by adding deoxynucleotides to the 3' end.
Synthesis occurs in 5' to 3'
Proofreads with 3' to 5' exonuclease
30
what does DNA polymerase 1 do?
Prokaryote, degrades RNA primer, and replaces with DNA
(has same functions as DNA polymerase III but also excises RNA primer with 5' to 3' exonuclase
31
Is DNA replication semiconservative?
Yes
32
Is DNA replication continuous or discontinuous?
It is both. Discontinuous fragments called Okazaki fragments
33
What is the use of DNA ligase?
Catalyzes the formation of phosphdiesterase bond within double stranded DNA
34
What is function of telomerase?
An RNA dependent DNA polymerase that adds DNA to 3' end of chromosome to prevent lose of genetic material with each replication (eukaryotes only)
35
Which DNA component is often desregulated within cancer?
Telomerase.
36
What are the severity of DNA damage?
silent
37
What is a transition DNA mutation?
Purine to purine (A to G, or C to T)
| or pyrimidine to pyrimidine
38
What is a transversion mutation?
Purine to pyfrimidine (A to T) or pyrimidine to purine (C to G)
39
What is a silent mutation?
Nucleotide subsitution, but same amino acid base coded
40
What is missense mutation?
Nucleotide substitution in changed amino acid but with similar chemical structure
(sickle cell)
41
What is a nonsense mutation?
Results in nucelotide with early stop
42
What is a frameshift?
| what are some diseases?
Deletion and insertion that causes misreading of all nucloetides downstream
1) Tay sachs, Duchesse muscular dystrophy
43
What is splice site?
Retrained intron in the mRNA (protein is imparied)
| Cancer, dementia, epilepsy, B thalasemmia
44
What is the Lac operon?
1) Genetic responses to environmental changes
2) Ecoli prefers glucose metabolism, when no glucose, switches to lactose metabolism
High lactose, unbinds the repressor protein from reprressor/operator site and has transcription.
The LAC genes are expressed when there is no glucose and lactose available.
LAC genes are low basal when high glucose, lactose available
LAC genes not expressed if high glucose, and no lactose
45
what are the types of DNA repair, and when in cell cycle do they occur?
1) Nucleotide excision
2) Base Excisions
3) Mismatch repair
46
What is base excision repair?
| When is this type of repair important?
Base specific glycosylase removes altered bases
Occurs throughout the cell cycle
Spontaneous or toxic deamination
47
what is nucleotide excision repair?
| What diseases are caused by defective?
1) Endonucleases release the oligonucleotides and DNA polymerase ligase and fill, and reseal gap
Occurs in the G1 phase
Xeroderma pigmentosum
48
What is a mismatch repair?
| What diseases?
Looks are the strand, and mismatched nucloetides are removed the gap is filled in.
Occurs during the G2 phase
Diseases: HNPCC
(also called Lynch syndrome)
49
What are mechanism of repairing double stranded DNA?
1) Non homologous end joining (2 ends of DNA fragments to repair double stranded breaks) some DNA maybe lost
2) DNA, RNA protein synthesis direction (if have drugs that attack the 3' end hydroxyl attack
50
what are the mRNA start codons?
AUG or GUG
51
what is difference between eukaryotes and prokaryotes codons?
Eukaroates code for methionine which may be removed before translation is completed
Prokaryotes: n-formylmethionine
52
What are mRNA stop codons?
UGA (u go away)
UAA (u are away)
UAG (u are gone)
53
What are the regulators of gene transcription?
1) Promoter (site were RNA polymerase II and transcription factors bind to DNA upstream from AT CAAT or TATA boxes
2) Enhancer: stretch of DNA factors that alter gene expression by binding to transcription factors
3) Silencer: site where negative regulators bind
54
What are the different types of RNA polymerase?
RNA polymerase 1 (makes mRNA, most rampant)
RNA polymerase 2 (makes mRNA, largest, MASSIVE)
RNA polymerase 3 (makes 5s, rRNA, tRNA): t is the smallest..TINY
55
what disease associated with RNA polymerase II?
alpha-amanitin (death cap mushrooms and causes heptotoxicity)
56
What medication is associated with inhibition of RNA polymerase?
Rifampin
57
what are the steps of RNA production?
1) Transcript is heterogenous (nuclear) becomes hmRNA when modified
2) Capping of 5' end with 7 methylguanosine cap
3) Polyadenylation of 3' end (200A)
4) Splicing out introns
CAPPED, SPLICED, and TAILED is MRNA
5) Transported out of nucleus into cytosol
6) P-bodies: exonuclease, and enzymes and stored for future use.
58
How does splicing of pre-mRNA occur?
1) Transcript combines with snRNP and other proteins to form spliceosome
2) Lariat shaped intermediate is formed
3) Lariat removed intron to join the two exons
59
What are the differences, intron vs exons?
Exons contain genetic information for coding of the protein.
Introns are intervening non coding segments of DNA
60
what are micro RNA?
Non coding portions of mRNA that regulate protein expression
(introns can contain the microRNA genes)
They can cause degredation, ot inactivation of target mRNA
61
what is the shape of tRNA?
1) Cloverleaf form
2) Long 3' end
3) T arm: ribosome binding
4) D arm: tRNA recognition for tRNA synthetase
62
what is the wobble?
Accurate base pairing is usually required in 2 first nucloetide positions of an mRNA, the 3rd wobble may code for the same amino acid (degeneracy of the genetic code).
63
How does initiation of protein synthesis from mRNA?
1) GTP hydrolysis that causes 40S + 60S and 80S to assemble
64
How does elongation of the protein occur?
1) Aminoacryl site: incoming
2) P site: accommodates growing peptide
3) E site holds empty tRNA as it exits.
rRNA catylizes peptide bond
Ribosomes advance nucleotide toward 3'end
65
How does termination occur?
Stop codon is recongized and the polypetide is released
66
What are some modifications that can occur in post translation of rNA?
Removal of N and C terminal peptides
67
What are some covalent alterations?
1) Phosporylation, glycosylation, hydroxylation, methylation, acetylation, ubiqitation
68
What are chaperone proteines?
Intracellular proteins (yeast, HSP 60) that are expressed at high temperatures to prevent denaturing and misfolding
69
what are parts of M phase?
prophase, prometaphase, metaphase, anaphase, telophase
70
what are the steps of cell cycle?
```
Synthesis
Mitaosis
G1 (growth)
G2
G0
```
71
Where do tumor suppressors act?
p53 induces p21 which inhibits cyclin dependent kinases (these are checkpoints) inactivates E2F
Mutations lead to Li-Fraumani syndrome
72
what cell types (in terms of divison)?
1) Permenent (remain in GO and regenerate from stem cells) cardiac, neurons, skeletal, muscles, RBX
2) Stable enter into G1 when stimulated: heptocytes, lymphocytes
3) Labile never have Go, keep dividing (bone marrow, gut epithelium, skin, hair, germ cells)
73
What is I-cell disease and features?
1) Lysosome storage disease.
Golgi apparatus does not phosporylate mannose residue, and proteins are secreted extracellular rather then to lysosomes
```
Clinical features:
Coarse facial features
Clouded corneas
Restircted joint movememt
High lysosomal enzymes
```
74
What defects in proteosomes have been linked to disease?
Ubiquitin-proteosome system have been implicated in Parkinsons (do not tag protein properly)
75
```
What diseases do the following stains identify?
Vimentin
DesMin
Cytokeratin
GFAP
Neurofilaments
```
Vimentin: mesnchymal tumors (sarcoma, endometrail carcinoma, renal cell carcinoma)
DesMin (muscle tumor, rhabdomyosarcoma)
Cytokeratin (epithelial tumors squamous cell carcinoma)
GFAP: astrocytoma, glioblastoma
Neurofilatments: neuronal tumors: neuroblastoma
76
What are drugs that act on microtubules?
1) Mebendazole : antihelminthic
2) Griseofulvin: antifungal
3) Cholchicine: antigout
4) Vincristine/ Vinblastine: anticancer
5) Paclitaxel: anticancer
77
What is the cilia structure?
9+2 microtubules doublets
78
What is Kartagner syndrome?
cilia dyskinesia (immotile cilia due to dynein arm defect, results in male and female infertility, increases risk of ectopic pregnancy.
79
What is the cellular mechanism of Ouabin, and Digoxin?
Ouabin (for hypotension and arrythmias) inhibits by binding to the K+ site
Digoxin: Inhibits Na-K ATPase which leads to Na/Ca inhibition
80
What diseases are associated with the following types of collagen defects?
Type 1: Bone (osteogenesis imperfecta type 1)
Type 2: Cartwolage
Type 3: Ehlers Danlos
Type 4: Alport syndrome, Goodpasture
81
What steps of collagen synthesis are specifically associated with diseases?
Collagen hydroxylation deficiency:scruvy
Glycosylation deficiency: osteogenesis imperfecta
Crosslinking: Ehlers Danlos, Menkes Disease
82
What are features of osteogenesis imperfecta?
1) Multiple fractures with little trauma
2) Blue sclera
3) Hearing loss
4) Opalescent teeth that wear easilt.
83
what are characteristics of Ehlers Danlos syndrome?
Inheritance is either dominenet or recessive
Classical (joint/skin) mutation in type 5 collagen
Vascular: Type 3 collagen (vascular and organ rupture)
84
Characteristics of Menkes disease?
1) Kinky hair
2) Growth retardation
3) Hypotonia
Impaired copper absorption (ATP74, Menkes protein is defective)
85
What disorders are linked to elastin?
1) Fibrillin 1( glycoprotein forms sheath around elastin) Marfan
2) Emphysema alpha antitrypsin defeciency (lack of elastase)
3) Wrinkles due to collagen and elastin decrease
86
How to polymerase cahin reaction work, and what diseases can be tested?
1) Amplifies a specific desired fragment of DNA
| 2) Good for neonatal HIV and herpes encephalitis
87
What types of blotting techniques are used? What are the diseases which are identified?
1) Southern blot DNA
2) Northern blot RNA (gene expression levels)
3) Western blot: protein (HIV)
4) Southwestern blot (DNA binding proteins)
88
what is flow cytometry used for, and what diseases?
1) Assess size, granularity, and protein expression
| 2) Hemtological abnormalities: paraxymal nocturnal hemoglobinuria, fetal RBC, CD4 count HIV
89
When are microarrays used?
Genetic testing, cancer mutations. DNA probes sent to thousands of nucleic acid sequences to identify specific mutations.
90
what are enzyme linked immunosrbent assay?
detects presence of antigen or antibody in the blood
| HBsAg or anti HB
91
what and when karytype is done?
1) Can be done on the sample of blood
2) For trisomies or sex chromosome disorder
3)
92
when you do flurosecence in situ hybridization, where does flourescence sighting indicate?
1) Microdeletion: no fluo at site compared to other chromosome
2) Translocation: fluo outside of the original chromosome
3) duplication: extra fluo on one chromosome relative to homologous
93
What are steps to cloning?
1) Isolate mRNA of interest
2) Expose mRNA to reverse transcriptase cDNA
3) Insert cDNA fragments into bacterial plasmids
4) Transform recombinant plasmids into bactera
5) Surviving bacterial on antibiotics produce cloned DNA
94
What is codiminece?
Both alleles contribute to phenotype (blood type, alpha antitrypsin deficiency)
95
Variable expressivity?
Same gentoype, but the expression of phenotype leads to different seriousness of disease ( neurofibrmatosis type 1)
96
Incomplete penetrance?
Not all the same mutant genotype show the mutant phenotype
BRACA1 does not always results in breast and ovarian cancer
97
Pleiotrophy?
One gene contributes to multiple phenotypes
Phenylketonuria (light skin, intellectual disability and musky body odor)
98
Anticipation?
Increased severity and earlier onset with generations
| 1) Huntington's disease
99
Loss of heteroziosity ?
1) Need mutation of the gene, and of the suppressor gene to get disease (2 hit)
2) Retinoblastoma
3) Lynch syndrome HNPCC
100
What is mosaicism and the disease associated?
1) Presence of gentically distinct cell lines within individual
2) Somatic: through multiple cell lines
3) Gonadal: only in egg and sperm cells
McCune-Albright syndrome: mutation of G protein (cafe au lait sports, early puberty, multiple endocrine abnormalities)
101
Locus heterogeneity?
Mutations in different loci, lead to similar disease: Albino
102
Allelic heterogenity?
Different loci mutations lead to the SAME disease
B-thalasssemia
103
What are assumptions of HArdy-Weinberg genetics?
1) No mutation at the locus
2) Natural selection not occuring
3) Random mating
4) No net migration
104
What is the equation and meaning of HArdy Winberg?
PP= homozygous for p allele
qq= homozygous for q allele
2pq: heterozygous
pp+2pq+ qq= 1
105
What is imprinting?
At some loci, only 1 allele is active
If that only allele is inactivated, causes disease
```
Parder-Willi syndrome
Angelman syndromes (chromosome 15)
```
106
Clinical effects of Prader-Willi syndrome?
1) Hyperphagia
2) Obesity
3) Intellectual disability
4) Hypogonadism
5) Hypotnia
25% cases due to 2 maternal imprinted genes and no father gene (the maternal is silent)
107
What is AngelMan syndrome?
Paternal imprinting (silent) and maternal one is defective
5% due to paternal uniparental disomy (the gene from mother not received)
108
What are modes of inhertiance and the disorders associated?
1) Autosomal dominant (many generations, male +female)
2) Autosomal recessive (usually only 1 generation)
3) X linked recessive (son of mother have 50% chance)
4)
X linked dominent (50% males and 50% daugthers) : hypophospatemic rickets, fragile X, Alport Syndrome
109
Mitochondrial inheritance?
All female offspring will have
| Rare syndromes: MELAS (mitochrondrial encephalopathy), lactic acidosis
110
Achondroplasia?
Autosomal dominenet
FGFR3 mutation
Dwarf, limbs affected more
111
Autosomal polycystic kidney?
Autosomal dominent
| PKD1 orPKD2, have large cysts on kidney
112
Familial adenomatous polyposis?
Autosomal dominenent
Colon full of polyps at puberrt
5q mutation
113
Familial hypercholesterol?
Autosomal dominent
Elevated LDL
corneal ulcers
Tendon xanthomas
114
Hereditary hemorraghic telangiectasia?
Auto.DOm
| Blood vessel disorder, branching skin lesions , AVM, GI bleeding
115
Hereditery spheretocytosis?
```
Auto.Dom
spheroid erythrocytosis (hemolytic anemia, treat by taking out spleen)
```
116
Huntington?
```
Auto.Dom
Depression
Choreform movements
Dementia
Increased dopamine, decreased GABA, decreased Ach
```
117
Li-Fraumani sydrome?
AutoDom.
| TP53 mutation, many malignacies at young age (Sarcome, breast, leukemia, adrenal gland)
118
Marfan syndrome?
Auto.Dom
| FBNI, pectus excavatum, tall, tapering fingers and toes, hypermobile joints
119
Multiple endocrine neoplasia?
Auto.Dom
Men 1
Men 2A and 2B with the RET gen
Familial tumors of endocrine glands: pancreas, parathyroid, adrenal medulla,
120
Neurofibroatosis type 1
Autosomal Dom.
| Cafe au lait spots, optic gliomas, cutaneous neurofibromas
121
Neurofibromatosis type 2?
```
Autosomal Dom.
Bilateral acoustic schwannomas
Juvenile cateracs
Meningiomsa
Chromosome 22
```
122
Tuberous sclerosis?
Numerous benign harmartomas
123
Von Hippel-Laudau disease?
Autosomal dom.
Numerous tumors both bengin and malignant
Associated with deletion of VHL (tumor suppressor)
3 words for chromosome 3
124
What are some examples of autosomal recessive disease?
1) Albino
2) Polykystic disease
3) cystic fibrosis
4) glycogen storage disease
5) mucopolysaccharidose
6) Phenylketonuria
7) Sickle cellanemia
8) Sphingolipidose
9) Thalassemias
10) Wilson disease
125
What are genetics of cystic fibrosis disease?
1) Recessive
2) Defect in CFTR gene (chromosome 7)
3) Deletion of Phe 508
most common lethal genetic disease in Caucasian population
126
what is the pathophysicology of cystic fibrosis?
1) Misfolded protein (transport protein)
2) Decreases secretion of Cl and increases absorption of NA and increase absortion of the H20
3) Abnormally thick secretion in the GI and the respiratory tract.
127
How is the diagnosis made?
1) Cl concentration more then 60 mEq/L
| 2) Immunoreactive trypsinogen in the newborn
128
what are the complications from cystic fibrosis?
1) recurrent pulmonary infections (S. Aureus), P. Aeruginosa
2) Pancreatic insufficiency (malabsorption, steatorrehea)
3) Bilary cirrhsos, and liver disease
4) Infertility in men (no vas deferens, spermatogenesis is affected)
5) Nasal polyps
129
What is the treatment of cystic fibrosis?
1) Chest physio
2) Albuterl
3) Aerosolized dornase alfa
4) Azithromyicin (anti-inflammatory for enzyme insufficiency
130
What are some x-linked recessive disorders?
1) Ornithine transcarbylase insufficiency
2) Fabry disease
3) Wiscott-Aldrich syndrome
4) G6PD deficiency
5) Hunter syndrome
6) Hemophilia A and B
7) Lesch-Nyhan syndrome
8) Duchenne and Becker dystophy
131
what is cause of duchenne dystrophy (genetic)
1) X-linked, frameshift (truncated dystophin protein)
132
what happens in Duchenne dystrophy?
1) Inhibited muscle regeneration
2) Starts at the pelvic girdle muscle and progresses superiorly
3) Pseudohypertrophy of the calf muscle due to fibrofatty replacement of the muscle
133
What maneuver defines Duchenne dystrophy?
1) Uses the upper extremities to help stand up
2) waddling gait
3) Dilated cardiomyopathy can cause death
134
what protein is not properly coded in Duchenne dystrophy?
Dystrophin gene is deleted
135
What is the test for Duchenne dystrophy?
1) Western blot
| 2) Muscle biopsy
136
what is the cause of Becker's disease?
1) Have a non-frameshift mutation
2) also dystropin gene (partially functional)
3) Less severe then Duchenne
4) Onset without adolescent
137
what type of genetic disease is myoclonic type 1?
which gene is affected?
which protein does not work?
1) Autosomal dominent
2) DMPK gene
3) myotonin protein
138
What are the symptoms of myotonic type 1?
1) Myotonia
2) muscle wasting
3) cataracts
4) testicular atrophy
5) frontal balding
6) arrythmia
139
What gene is responsible for fragile x syndrome?
1) FMR1 (methylation and over expression)
140
What are signs of fragile x syndrome?
1) Intellectual disabity
2) enlarged testes (post-pubertal macroorchidsim)
3) large face
4) long jaw
5) large everted ears
6) autism
7) mitral valve prolapse
141
Menomic to remember the trinucleotide issues with the following diseases:
```
Huntington disease
Fragile x syndrome
Frederich ataxia
Huntington disease
Myotonic dystrophy
```
```
X-Girlfriend First Aid Helped Ace My Test
Fragile x (X-G) cGg
Frederich ataces (F-A) gAg
Huntington disease (H-A) cAg
Myotonic dystrophy (M-T) cTg
```
142
What is the genetic cause of Down's syndrome?
1) Meiotic non-disjunction (95%)
| 2) Unbalanced Robertsonian transolocation (chromosome 14 and 21)
143
What is the incidence of Down's syndrome?
Incidence 1:700
144
What are pre-natal tests for Down's syndrome? (first trimester) and then second trimester
First trimester
1) increased nuchal translucency
2) hypoplastic nasal bone
3) Decreased serum PAPP-A
4) Increased free b-hcg
Second trimester:
1) Decreased alpha fetoprotei
2) Increased B0hcg
3) Decreased estriol
4) Increased inhibin A
145
What is genetic defect for Edwards syndrome?
| What is the incidence of Edwards syndrome?
Trisomy 18
| 1:8000
146
What are the features of Edward's syndrome?
1) Intellectual disability
2) Rocker bottom feet
3) Micrognathia (small jaw(
4) Low set ears
5) Clenched hands with overlapping fingers
6) Prominent occiput
7) Congenital heart disease
8) Death within 1 year of birth
147
What are prenatal tests showing for this disease?
First semester:
1) PAPP-A decreased
2) Decreased B HCG (Down's is increased(
Second trimester:
1) Decreased alpha feto protein
2) Decreased b HCG
3) Decresed estriol
4) Decreased or normal inhibin A
148
What is the genetic of Patau syndrome?
1) Trisomy 13
149
What is the incidence of Patau syndrome?
1:15000
150
What are the clinical features of Patau syndrome?
1) Intellectual disaility
2) Rocker bottom feet
3) Mircopthalmia
4) Microcephaly
5) Cleft lip
6) Cleft palate
7) Polyadctyl
8) Congential heart disease
9) Death within 1 year
151
What tests are abnormal in the Patau syndrome?
1) B HCG
2) PAPP-A
both are decreased
152
Chromosome abnormality for von Hippel Laudau and renal cell carcinoma ?
Chromosome 3
153
Chromosone for PKD2, achondroplasia and Huntington?
Chromosome 4
154
Chromosome from Cri-de-chat?
Chromsome 5
155
Chromsoms for hemocrhomatosis?
Chromosome 6
156
Chromosome for Williams and Cystic fibrosis?
Chromosome 7
157
Chromsome for Frederich ataxia
Chromosome 9
158
Chromsome for Wilms tumor, B globin gene defects
Chromosome 11
159
Chromosome Patau syndroms, Wilson, retinoblastomia ?
Chromosome 13
160
Chromosome for Prader-Wilii, Angelman, Marfan?
Chromosome 15
161
Chromosome for ADPKD, alpha globin, gene defect, thalassemia?
Chromosome 16
162
Chromosome neurofibromatosis, BRCA 1?
Chromosome 17
163
Chromosome fro Edwards syndrome?
Chromosome 18
164
Chromosome for Down's Syndrome ?
Chromosome 21
165
Chromosome for Neurofibromatosis type 2, Digeorge syndrome? (22q11)
Chromosoms 22
166
What does a Robertson translocation look like?
| What happens if it is balanced/unbalanced?
1) Long arms of the chromosome fuse to the centromere and two short arms are lost
2) Balanced translocation are less bad
3) Unbalanced translocation lead to miscarriage, stillbirth, and chromosomal imbalances
167
What are the deletion for cri-de-chat syndrome?
| What are clinical features?
1) Microdeletion of short arm for chromosome 5 (46 XX or XY)
2) Clinical features:
a) Severe intellectual disability
b) high pitched mewing and crying
c) epicanthal folds (corner of eyes)
d) Cardiac abnormalities
168
What is Williams syndrome?
| What are the clinical features?
1) Microdelation of long arm (chromosome 7)
2) Elfin features
3) Intellectual disability
4) Hypercalcemia
5) Well developped verbal skills, very friendly with strangers
6) Cardiovascular problems.
169
What is the 22q11 deletion?
| What is the clinical symptoms?
Microdeletion of 22q11
2) Cleft palate
3) Thymic Aplasia (T Cell deficiency)
4) Parathyroid aplasia (hypocalcemia)
5) Digeorges syndrome: thymic, parathyroid, and cardiac defects
6) Velocardiofacial syndrome: palate, facial, and cardiac defects
170
What are the fat soluable vitamins?
ADEK
171
Why are the fat soluable vitamins more likely to have toxicity?
Have tendency to accumulate in fat
172
What type of absorption syndromes will cause fat soluble deficiency?
1) Absorption with steatorrhea (cystic fibrosis, sprue, mineral oil intake)
173
which are the water soluable vitamins ?
```
B1 (thaimine, TPP)
B2 (riboflavin)
B3 (niacin, NAD+)
B5 (pantothenic acid: CoA)
B6 (pyridoxine PLP)
B7 (biotin)
B9 (folate)
B12 (cobalamine)
C (ascorbic acid)
```
174
Water soluable vitamins are washed out easily from the body, which ones are not? for how long?
B12 (in liver for 3-4 years)
| B9 (liver for 3-4 months)
175
What are symptoms of B 12 complex deficiencies?
1) Dermatitis
2) Glossitis
3) Diarrhea
176
Watersoluable vitamins are precursors to what organic cofactors?
FAD and NAD+
177
What are the functions of vitamine A (retinol)?
1) Antioxidant
2) Retinal pigmanets
3) Differentiation of epithelial cells into specialized tissue (pancreatic cells, mucous-secreting cells)
178
What problems do retinol A treat?
1) Acne and wrinkles
2) isoretinoin cystic acne
3) All trans-retinoic acid to treat acute promyelocytic leukemia.
179
What happens if have retinol A deficiency?
1) Night blindness
2) Xdry scaly skin (Xerorsis cutis)
3) Corneal degeneration
4) Blind spots on conjunctiva
180
what happens if you have too much retinol A?
1) Nausa, vomit
2) Vertigo, blurred vision
3) Alopecia, dry skin
4) Hepatic toxicity
5) teratogenic (cleft palate, cardiac abnromal)
before giving isotertinoin need pregnanct test and two forms of birth control.
181
What is Vitamin B1 (thiamine) a cofactor for?
1) Pyruvate dehydrogenase TCA cycle
2) alpha ketoglutarate dehydrogenase (TCA)
3) Transketolase (HMP shunt)
4) Branched-chain ketoacid dehydrogenase
182
What are the diseases caused by B1?
1) Wernicke-Korsokoff; confusion, ataxia, confabulation,damage to the mammillary bodies
2) Dry beriberi: polyneuritis, symmetric muscle wasting
3) Wet beriberi: high output cardiac failure
183
What is the physiopathology of vitamin B deficinecy?
1) Imparied glucose breakdown (ATP depletion)
| 2) Seen in malnutrition and ETOH
184
How is diagnosis of vitamin B deficiency diagnosed?
1) Increased RBC transketolase activity following B1 adminstration
185
What is the function of Vitamin B2 (riboflavin)?
1) Component of FAD and FMN
186
what are the clinical signs of B2 deficiency?
1) Cheilosis (inflammation anc scaling of fissures)
| 2) Corneal vascularisation
187
What is the function of B3 (niacin)?
Constuent of NAD+ and NADP+
188
What are the clinical functions of B3?
They can be used to lower the levels of VLDL and raise levels of HDL.
189
What are clinical problems associated with B3 deficiency?
1) Glossitis
2) Severe can lead to pellgra (scaly red skin that looks like venous insufficiency)
3) Hartnup disease
```
Symptoms of pellegra include:
Diarrhea
Dementia
Dermatitis
Hyperpigementation of the limbs
```
Characteristics of Hartnup disease:
1) Autosomal recessive
2) Deficiency of neutral amino acid
190
What is the treatment for pellegra?
1) High protein diet
| 2) Nicotinic acid
191
What is Hartnup disease?
1) Autosomal recessive
2) Deficiency of neutral amino acids (tryptophan), with decrease tryptophan absorption in the gut, which leads to decrease transformation to niacin. This will lead to pellagra
192
What is the function of vitamin B5 (pentothenic acid)?
1) essential for coenzyme A
| 2) For synthesis of fatty acids
193
What is the function of vitamin B6 (pyridoxine)?
1) Converted to pyridoxal phosphate which is used for:
a) ALT and AST
b) synthesis of heme
c) Synthesis of neurotransmittors including serotonin, epinephrine, norepinhrine, dopamine, and GABA
194
What happens in deficiency of B6?
1) Convulsions
2) Irritability
3) Peripheral neuropathy
4) Sideoblastic anemia
195
what does Vitamin B7 do?
Cofactor for carboxylation enzymes (adds a C group)
1) Pyruvate (3C) to oxaloacetate (4C)
2) Acetyl CoA carboxylase (2c) to malonyl CoA (3C)
3) Propionyl-CoA carboxylase (3C) to methylmalonyl CoA
196
How do deficiency of B7 manifest?
1) Dermatitis
2) Alopecia
3) Enteritis
Usually due to excessive ingestion of egg whites
197
what is the function of vitamin B9 folate?
Converted to tetrahydrogolic acid (THF), important for DNA and RNA
198
Where does B9 (folate come from)?
Leafy green vegetables
199
What are diseases assocaited with Vitamin B9 deficiency?
1) Macrocytic anemia
2) Megaloblastic anemia
3) Hypersegmented polymorphonuclear cells
4) Glossitis
200
What is seen on vitamin B9 deficiency?
1) Increased homocyteine levels
| 2) Normal methylmalonic acid
201
What are causes of B9 deficiency?
1) Phenyltoin
2) sulfonamides
3) Methotrexate
202
What is the function of vitamin B12 (Cobalamin)
Cofactor for methoine synthesis
203
What diseases are associated with B12 deficiency?
1) Macrocytic anemia
2) Megaloblastic anemia
3) Hypersegmented PMN
204
what are causes of B12 deficiency?
1) Malabsorption (sprue, enteritis)
2) Crohn
3) Lack of terminal ileum
4) Pernacious anemia
205
What is function of ascorbic acid?
1) Antioxident
2) Facilitates absorption of FE
3) Hydroxylation of prolene and lysine
4) Needed to make dopamine and B-hydroxylase
206
What disease is caused by vitamin C deficiency?
Scruvy (swollen gums, bruising, petechiae, perifollicular and subperiosteal hemorrage)
Vitamin C defect, causes Scurvy due to Collagen synthesis deficiency.
207
What are the two types of vitamin D and where do they come from?
D2: ergocalciferol (ingested from plants)
D3: Cholecalciferol (consumed in milk, formed in sun-exposed skin)
208
What is the storage form of vitamin D ?
| What is the active form?
25-OH D3 (storage form)
| 1,25 (OH)2 D3 (calcitriol) active form
209
How does vitamin D function?
1) Increases intestinl absorption of calcium and phosphate
2) Increase bone mineralization at low levels
3) Increased bone absorption at higher levels
210
What happens if there is vitamin D deficiency? (children vs adults)
1) Children: rickets (bone pain, deformity)
2) OSteomalacia : bone pain and muscle pain
3) Hypocalcemia: tetany
211
What excabates vitamin D deficiency?
1) low sun exposure
2) pigmented skin
3) prematurity
212
What are symptoms of excess vitamin D?
1) Hypercalcemia
2) Hypercalcinuria
3) Loss of appetite
4) Stupor
213
What is the function of vitamin E ?
| What i effect on warfarin?
1) Antioxident (protects RBC and membranes)
| 2) Enhances effect of warfarin
214
How is vitamin E deficiency manifest itself?
1) Hemolytic anemia
2) Acanthycytosis
3) Muscle weakness
4) Spinocerebeller tract demeylination
215
How to differentiate between vitamin E and vitamin B12 deficiency?
Have neurological presentation (but vitamin E does not have megaloblastic anemia or hypersegmented PMN, or increased methylmalonic acid.
216
What are function of vitamin K?
Cofactor for glutamic acid, synthesizes the proteins required for blood clotting
217
What factors of blood clotting are affected by vitamin K?
II, 9, 7, 2, 10
Protein C
Protein S
218
Why are newborns given vitamin K injection at birth?
1) To prevent hemorrhagic disease
2) Have elevated Pt and aPTT (normal bleeding times)
3) Have sterile intestines, and can't synthesize vitamin K
219
What is the function of zinc?
1) essential for activity of 100 enzymes
220
what are consequences of zinc deficeincy?
1) Delayed wound healing
2) Decreased adult hair (axillary, facial)
3) Acrodermatitis enteropathica
221
What are two conditions that result from malnutrition?
1) Kwashiokor
| 2) Marasmus
222
What are the clinical symptoms of Kwashiokor?
1) Malnutrition
2) Edema
3) Anemia
4) Fatty liver
(theink of child with swollen abdomen)
223
What are cause of marasmus and the clinical symptoms?
1) Insuffiient calories (loss of tissue, and muscle wasting)
224
What chemical causes ETOH hangover?
Accumulation of acetaldehyde
225
How does ethanol affect the NADh/NAD +ratio in the liver?
1) Increases the ratio of NADH/NAD+
2) Causes: a) lactic acidosis
b) fastin hypoglycemia
c) heptosteatosis
226
How many ATP does aerobic metabolism produce?
1) 32 ATP through malate/aspertate shuttle (heart+ liver)
| 2) 30 ATP through glycerol 3-phosphate (muscle)
227
How many ATP for anaerobic metobolism?
1) 2 net ATP
228
What is cause of fructosuria?
1) Autosomal recessive(defect in fructokinase)
| 2) Fructose appears in the blood and urine
229
What is fructose intolerance?
What are symptoms?
What is treatment ?
1) Deficiency in aldolase B (autosomal recessive)
2) Leads to accumulation of fructose-1-phosphate which inhibits glycogeneolysis and glucogenesis
3) Hypoglycemia, jaundice, cirrhosis, vomiting
4) Treatment is to decrease fructose and sucrose intake.
230
What is galactokinase deficiency?
Deficiency of galactokinase, causes accumulation of galactitol (autosomal recessive)
231
what are symptoms of galactokinase deficiency?
1) Galacititol accumulates in the body
2) Usually mild condition, autosomal recessive
3) Galactose appears in the blood, and in the urine
4) Infantile cataracts, intellectual disability
232
what is treatment for galactokinase deficiency?
1) Relatively mild (autosomal recessive)
233
what is classic galactosemia?
1) Absence of galactose-1-phosphate uridyltransferase.
234
What are the symptoms of classic galactosemia?
1) Failure to thrive
2) Jaundice
3) Hepatomegaly
4) Infantile cateracts
5) Intellectual disabillty
6) Can cause e coli sepsis
235
What is the pertinence of sorbital in diabetes?
1) glucose vs (aldose reductase) is converted to sorbitol.
2) If the tissue doesn't have enough enzymes for this transformation, can have accumulation with osmotic damage (cataracts, retinopathy, periphereal neuropathy)
236
Where does lactase act?
1) on the brush border to digest lactose
237
In what type of people is it common?
2) Asian
3) African
4) Native American
238
What are the types of lactase deficiency?
1) Insufficient lactase enzyme
2) Primary: age dependent decline after childhood
3) Secondary: loss of brush border due to gastroenteririts
4) Congenital
239
What do patients with lactase deficiency show?
1) Stool with low PH
2) Breath with high hydrogen content
3) If patient has herreditary lactose intolerance, the biospy will be normal.
240
What are the symptoms and treatment for lactose deficiency?
1) Bloating
2) Cramps
3) Flatulence
4) Osmotic diarrhea
Treatment:
1) Avoid dairy product
2) Lactose pills
3) Lactose free milk.
241
what are the different amino acids?
1) essential
2) Acidic
3) Basic
Essential:
Glucogenic:
1) Methionine
2) Valine
3) Histidine
Glucogenic/ketogenic:
1) Isoleucine (Ile)
2) Phenylalanine (Phe)
3) Threonine (Thr)
4) Tryptophan (Trp)
5) Ketogenic : Leucine, lysine
Acidic:
1) Aspartic
2) Glutamic (Glu)
Basic:
1) Arginine
2) Lysince
3) Histadine
242
What are enzymes of urea cycle?
1) Ordinar Careless Crapper are Also Frivolous About Urination
```
Ornithine
Citrulline
Aspartate
Arginosuccinate
Fumarate
Urea
```
243
How is ammonia processed in the body?
1) Occurs in the muscle first and then the liver
2) The cahill cycle and the cori cycle link the muscles to the liver.
3) Starts with ammonia, and after processed by muscle and the liver, results in urea.
244
What are signs of hyperammonia?
1) Tremor (asterix)
2) Slurring speech
3) Somnolence
4) Cerebral edema
5) Blurring of vision
245
What happens (cellular level) when the ammonia accumulates?
1) Depletes alpha ketoglutate, leading to inhibition of TCA cycle
246
What are possible treatments for high levels of ammonia?
1) Lactulose to acidfy the GI tract and trap NH3 for excretion
2) Rifaximin to decrease colonic ammoniagenic bacteria
3) Benxoate, phenylacetate, or phenylbutyrate to bind the ammonia.
247
What is N-acetylglutamate synthase deficiency?
Causes hyperammonia
248
What is orinthine transcarbylase deficiency?
| What are findings?
1) X linked recessive
2) Interferes with body's ability to eliminate ammonia
Findings:
1) Increase orotic acid in blood and urine
2) Decrease BUN
249
what are the derivatives of the following amino acids?
1) Phenylalanine
2) Tryptophan
3) Histidine
4) Glycine
5) Glutamate
6) Arginine
Phenyalanine- NE and epi
Tryptophan NAD, NADP+, Serotonin, Melatonin
Histidine: Histamine
Glycine: Heme
Glutamate: GABA and glutatione
Arginine: Creatinine, Urea, Nitric oxide.
250
What is phenyketonuria?
1) Decreased phenylalanine hydorxylase----> phenylalanine---> excess phenylketones in urine
251
What are symtoms of phenylketonuria?
1) Intellectual disability
2) Growth retardation
3) Seizures
4) Fair skin
5) Eczema
6) Musty body odor
252
If there is maternal PKU (not properly treated)?
1) Microcephaly
2) Intellectual disability
3) Growth retardation
4) congential heat defect
253
What are the genetics of PKU?
1) Avoid aspartame
254
When and why should newborns be screened for PKU?
2-3 days after birth (before that the maternal enzyme is being used)
255
What is a distinguishing characteristic of PKU?
1) Has a musty body odor.
256
What is the basis of Maple Syrup urine disease?
1) Blocked degradation of branched amino acids (isoleucine, leucine, valine)
2) Increase ketoacids in the blood
257
What are the symptoms of maple syrup disease?
1) CNS defects
2) intellectual disability
3) Death
258
How to treat maple syrup urine disease?
1) Restrict isoleucine
Leucine
Valine
Thiamine
259
What is alkaptonuria?
1) Congential deficinecy of homogentisate oxidase
2) Recessive
3) Usually benign
260
What are the symptoms of alkaptonuria?
1) Blue-black connective tissue and sclera
2) Urine turns black when exposed to air
3) Painful arthalgias
261
What is homocytinuria types?
1) Cystathionine synthase deficiency
Treatement:decrease methionine, increase cysteine, incease B12
2) Methionine synthase deficiency (Increase mehtionin in the diet)
262
what are symptoms of homocystinuria disease?
1) Increased homocysteine in the urine
2) intellectual disability
3) Osteoporosis
4) Kyphosis
5) Thrombosis
6) Mi
263
What is the cause of cystinuria?
1) Hereditary defect of renal PCT and intestinal amino acid transporter that prevents resorption of cysteine, ornthine, lysine, arginine
2) Autosomal recessive (common 1:7000)
264
How to test for cystinuria?
Urinary cyanide-nitroprusside test
265
What is the treatment of Cystinuria?
1) Urine Alkanization (K, citrate, acetazolamide)
| 2) Chelating agents: penicillmine
266
What are the signs of cystinuria?
1) Reccurrent precipitation of hexagonal cysteine stones.
267
How is glycogen regulated by epinephrine?
Epinephrine activates the glucagon receptor, which will transform glycogen to glucose (this occurs within the muscle or the liver)
268
There are 12 tyoes of glycogen storage disease, what type of stain is used to identfy them?
Periodic acid (Schiff stain)
269
What are the types of liver storage diease ?
1) Von Gierke's disease
(fasting hypoglycemia, increased glycogen in the liver. )
Increase uric acid, heptomegaliy
: Glucose-6-phosphate
Treatement: oral glucose, and cornstarch
Has imparied glucogenesis
2) Pompe disease (deficient lysosomal 1,4 glucosidase)
Hypertrophic cardiomegaly
Exercise intolerance
Pomp trashed the pump (heart, liver, and muslce)
3) Cori disease (deficiency 1,6 glucosidase) mild accumulation of dextrin, and glucogenesis is intact
4) McArdle disease: (myophophorylase deficient)
Increased glycogen in the muscle, leading to painful muscle cramp and myoglobinuria i the urine
270
Name the lysosomal storage diseases?
1) Fabry disease ( alpha galactosidase)
2) Gaucher disease (Glucocerebrosidase)
3) Niemann-pick disease: sphingomyelinase
4) Tay-Sachs: Hexosaminidase
5) Krabbe disease : galacroberbroidase
6) Metachromatic leukodystrophy: arylsulfase
271
What type of metabolism occurs after being fed?
| Which hormone is acting?
1) Glycolysis
2) Aerobic respiration
Insulin stiumulates storage of lipids, proteins, and glycogen
272
What is the type of metabolism fasting (between meals)?
| Which hormone is acting?
1) Hepatic glycoenesis (major)
2) Hepatic glucognesis
Homrone: glucagon, and epinephrine which use fuel reserves
273
What type of metabolism after 1-3 days of starvation?
1) Hepatic glycogenolysis
2) Adipose release of FFA
3) Muscle and liver
4) Hepatic glucogenesis from peripheral lactate and alanine
274
What is the metabolism after day 3 of starvation?
Adipose stores (ketone bodies) are the main source of energy
| amount of stores determines survival time
275
What is the use of cholesterol?
1) Production of bile, steroids, and vitamin D
276
Which enzyme is responsible for cholesterol synthesis?
1) HMG-CoA
| statins reversibly inhibit this enzyme
277
what are the two types of lipoproteins? What are they responsible for?
LDL: cholesterol from the liver to tissues
HDL: cholesterol from the tissues to the livr
(H D L is healthy)
278
What are the familial types of dyslipidemia?
1) Hyperchylomicronemia
2) Familial hypercholesterolemia
3) Hypertriglyceridemia
279
What is the clinical picture of each kind of familial dyslipidemia?
1) Hyperchylomicronemia: Pancreatitis, hepatosplenomegaly, eruptive xanthomas
2) Familial hypercholestolemia (LDL, cholesterol) : MI before 20, tendon xanthomas, corneal arcus
3) Hypertriglyceridemia (VLDL, TG) acute pancreatitis.
