First Aid Biochem Flashcards
(237 cards)
1
Q
Histones are rich in what amino acids?
A
lysine and arginine
2
Q
How does H1 stabilize the chromatin fiber?
A
H1 binds to the nucleosome and to “linker DNA”
3
Q
What proteins make up a nucleosome?
A
(H2A, H2B, H3, H4) x2
4
Q
What are Barr bodies?
A
inactive X chromosomes; heterochromatin
5
Q
What allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes?
What happens at CpG islands?
A
template strand cytosine and adenine are methylated in DNA replication
DNA methylation at CpG islands represses transcription
6
Q
What does histone methylation cause?
A
usually reversibly represses DNA transcription, but can activate it in some cases depending on methylation location
7
Q
What relaxes DNA coiling, allowing for transcription?
A
histone acetylation
8
Q
What drugs disrupt pyrimidine synthesis?
A
leflunomide, methotrexate, TMP, pyrimethamine
9
Q
de novo pyrimidine base production requires what amino acid?
A
aspartate
10
Q
what does leflunomide inhibit?
A
pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase
(creating orotic acid from carbamoyl phosphate and aspartate)
11
Q
methotrexate, trimethoprim, and pyrimethamine all do what to inhibit pyrimidine synthesis
A
inhibit dihydrofolate reductase
(decrease deoxythymidine monophosphate (dTMP) in humans, bacteria, and protozoa, respectively)
12
Q
what forms 5-F-dUMP? what does this do?
A
5-fluorouracil (5-FU) inhibits pyrimidine synthesis by forming 5-F-dUMP, which inhibits thymidylate synthase
13
Q
What drugs disrupt purine synthesis?
A
6-MP and mycophenolate and ribavirin
14
Q
What is the prodrug of 6-MP? What do they both do?
A
azathioprine
inhibit purine synthesis by inhibiting PRPP from becoming IMP
15
Q
how does mycophenolate and ribavirin work?
A
inhibit ionosine monophosphate dehydrogenase from becoming GMP
16
Q
What drug inhibits purine and pyrimidine synthesis? How does this work?
A
hydroxyurea - inhibits ribonucleotide reductase
17
Q
what does de novo purine base production require?
A
aspartate, glycine, glutamine, and THF
18
Q
deamination of cytosine makes
A
uracil
19
Q
deamination of adenine makes
A
guanine
20
Q
methylation of uracil makes
A
thymine
21
Q
One of the major causes of autosomal recessive SCID, this is required for degradation of adenosine and deoxyadenosine…
What happens in deficiency of this enzyme?
A
adenosine deaminase deficiency
increased dATP leads to toxicity in lymphocytes
22
Q
In Lesch- Nyhan syndrome, there is defective purine salvage due to…
what does this normally do?
ssx?
A
due to absent HGPRT
converts hypoxanthine to IMP and guanine to GMP
exess uric acid production and de novo purine synthesis – hyperuricemia, gout, aggression/self-mutilation, retardation, dystonia
23
Q
“orange sand” in diaper is actually…
A
sodium urate crystals, a sign of Lesch-Nyhan syndrome
24
Q
What amino acids are specified by only one codon?
A
methionine - AUG
tryptophan - UGG
25
Origin of replication in eukaryotes and prokaryotes differs because...
in eukaryotes there are multiple origins of replication
26
What is the Y shaped region along DNA template?
what happens here?
replication fork
leading and lagging strands are synthesized
27
what prevents strands from reannealing?
single-stranded binding proteins (SSBPs)
28
what creates a single or double strand break in the helix to add or remove supercoils?
DNA topoisomerases
29
What drugs inhibit eukaryotic topoisomerase I?
irinotecan and topotecan
30
what drugs inhibit eukaryotic topoisomerase II?
etoposide and teniposide
31
what drugs inhibit prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV?
fluoroquinolones
32
Primase makes an RNA primer on which ...
DNA polymerase III can initiate replication
33
In prokaryotes only, this enzyme will elongate the leading strand by adding deoxynucleotides to the 3' end. It also elongates the lagging strand until it reaches primer of preceding fragment.
DNA polymerase III
34
What kind of synthesis and exonuclease power does DNA polymerase III have?
has 5' to 3' synthesis and proofreads with 3'-5' exonucleases
35
What is the modification in most drugs that block DNA replication?
modified 3' OH, preventing the addition of the next nucleotide, chain termination
36
What enzyme is prokayotic only and degrades the RNA primer to replace it with DNA? How does it do this?
DNA polymerase I
same function as DNA polymerase III, also exises RNA primer with 5' to 3' exonuclease
37
What enzyme catalyzes the formation of a phosphodiester bond within a strand of dsDNA?
what is this doing?
DNA ligase
joins Okazaki fragments
38
in eukaryotes only, this enzyme is an RNA-dependent DNA polymerase that adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication
when is this an issue?
telomerase
often dysregulated in cancer cells allowing unlimited replication
39
transition v transversion in DNA mutation
transition is purine to purine or pyrimidine to pyrimidine
transversion is purine to pyrimidine or vice versa
40
nucleotide substitution resulting in changed amino acid
missense
41
What ares two disease examples with frameshift mutations?
Duchenne MD and Tay-Sachs
42
What is the purpose of the lac operon?
What is the mechanism of this shift?
* genetic response to an environmental change
* glucose preffered metabolis substrate for E. coli, but when it is absent and lactose is available, the lac operon is activated to switch to lactose metabolism
* low glucose
* increase adenylate cyclase activity
* increase generation of cAMP from ATP
* activation of catabolite activator protein (CAP)
* increase transcription
* high lactose
* unbinds repressor protein from repressor/operator site
* increase transcription
43
What repairs bulky-helix distorting lesions? What phase of the cell cycle does this happen in? When is this defective?
nucleotide excision repair
G1 phase
defective in xeroderma pigmentosum
44
How does base excision repair work? When does it occur?
* base-specific Glycosylase removes altered base and creates AP (apurinic or apyrimidinic) site
* one or more nucleotides removed by AP-Endonuclease
* cleaves at 5' end
* Lyase cleaves at 3' end
* DNA polymerase-B fills the gap
* DNA ligase seals it
occurs through cell cycle
45
When does mismatch repair occur in the cell cycle?
G2 phase of cell cycle
46
What brings together 2 ends of DNA fragments to repair double stranded breaks?
When is this defective?
nonhomologous end joining
defective in ataxia telangiectasia, breast/ovarian cancers with BRCA1 mutation, and Fanconi anemia
47
What binds at the DNA promoter regions?
RNA polymerase II and multiple other transcription factors
48
RNA polymerases make what in eukaryotes?
* RNA polymerase I makes rRNA (most numerous - rampant)
* RNA polymerase II makes mRNA (largest - massive)
* mRNA read 5' to 3'
* opens DNA at promoter site
* RNA polymerase III makes 5sRNA, tRNA (smallest RNA, tiny)
no proofreading function, but can initiate chains
49
What drug inhibits DNA-dependent RNA polymerase in prokaryotes?
rifampin
50
What is found in death cap mushrooms and why is this toxic?
alpha-amanitin - found in Amanita phalloides
inhibits RN polymerase II
severe hepatotoxicity
51
What does RNA start as and then how is it modified in the nucleus?
hnRNA (heterogenous nuclear)
capping 5' end, polyadenylation of 3' end, splicing out of introns =\> mRNA
52
What happens to mRNA in the cytosol?
translated
quality control occurs at cytoplasmic processing bodies called P bodies which contain exonucleases, decapping enzymes, and microRNAs
53
Where can mRNA be stored for future translation?
P bodies in the cytoplasm
54
What forms a spliceosome?
primary transcript combines with small nuclear ribonucleotides (snRNPs) and other proteins to form spliceosome
55
Antibodies to splicesomal snRNPs are aka ....
and are highly specific for...
anti-Smith abs; SLE
56
Anti-U1 RNP abs are high associated with ...
mixed connective tissue disease
57
What posttranscriptionally regulate gene expression by targeting the 3' untranslated region of specific mRNAs for degradation or translational repression?
microRNAs
58
What are the arms of tRNA for?
* CCA at 3' end along with a high percentage of chemically modified bases - covalently binds amino acid
* T arm has TŶC (ribothymidine, pseudouridine, cytidine) tethers tRNA molecule to ribosome
* D arm contains dihydrouridine residues - detects the tRNA by aminoacyl-tRNA synthetase
59
What is responsible for accuracy of amino acid selection?
aminoacyl-tRNA synthetase and binding of charged tRNA to the codon
60
protein synthesis initiation
initiated by GTP hydrolysis; initiation factors (eukaryotic IFs) help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal 60S subunit assemble with the complex
61
Protein synthesis elongation stage
1. aminoacyl-tRNA binds to A site (except for initiator methionine
2. rRNA (ribozyme) catalyzes peptide bond formation, transfers growing polypeptide to amino acid in A site
3. ribosome advances 3 nucleotides toward 3' end of mRNA, moving peptidyl tRNA to P site (translocation)
62
Summary of sites in protein synthesis
A site: incoming aminoacyl-tRNA
P site: accomodoates growing peptides
E site: holds empty tRNA as it exits
63
Protein synthesis termination
stop codon is recognized by release factor and completed peptide is released from the ribosome
64
Posttranslational modifications include.../
trimming - remove N or C terminal peptides from zymogen to generate mature peptides
covalent alterations - phosphorylation, glycosylation, hydroxylation, methlyation, acetylation, and ubiquitination
65
intracellular protein involved inf acilitating and/or maintaining protein folding
example?
chaperone protein
eg in yeast, heat shock proteins - HSP60 - expressed at high temps to prevent protein denaturing/misfolding
66
What mediates check points in the cell cycle?
cyclins, CDKs - cyclin dependent kinases, and tumor suppressors
67
what phosphorylates other proteins to coordinate cell cycle progression?
cyclin-CDK complexes
68
how are CDKs inhibited?
p53 induces p21 to inhibit CDK
hypophosphorylation (activation) of Rb
inhibition of G1-S progression
69
What types of cells remain in G0 and regenerate from stem cells? What are examples of these cells?
permanent cell type
neurons, skeletal and cardiac muscle, RBCs
70
What type of cells enter G1 from G0 when stimulated?
What are examples of these cells?
stable (quiescent) cells
hepatocytes and lymphocytes
71
What cells never go to G0, but divide rapidly with a short G1?
What are examples of these cells?
labile type cells
bone marrow, gut epithelium, skin, hair follicles, germ cells
72
How does the Golgi modify some amino acids?
* modifies N-oligosaccharides on asparagine
* adds O-oligosaccharides on serine and threonine
* adds mannose-6-phosphate to proteins for trafficking to lysosomes
73
what are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use?
endosomes
74
What happens in I-cell disease?
inclusion cell disease/mucolipidosis type II
* inherited lysosomal storage disorder
* defect in N-acetylglucosaminyl-1-phosphotransferase
* failure of Golgi to phosphorylate mannose residues on glycoproteins
* proteins are secreted extracellularly rather than delivered to lysosomes
75
How does I cell disease present?
coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes
often fatal in childhood
76
abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER;
what happens if this is absent or dysfunctional?
signal recognition particle (SRP)
proteins accumulate in the cytosol
77
What are vesicular trafficking proteins?
* COP1: Golgi to Golgi (retrograde); cis-Golgi to ER
* COPII: ER to cis-Golgi (anterograde)
* Clathrin: trans-Golgi to lysosomes; plasma membrane to endosomes (receptor mediated endocytosis) eg LDL receptor activity
78
what organelle is involved in catabolism of very long chain fatty acids, branched-chain fatty acids, amino acids and ethanol?
peroxisome
79
What are some examples of peroxisomal disease and presentation?
* deficits in synthesis of plasmalogens, important phospholipids in myelin
* Zellwger syndrome
* hypotonia, hepatomegaly, early death
* Refsum disease
* scaly skin, ataxia, cataracts/night blindness, shortening of fourth toe, epiphyseal dysplasia
80
what degrades ubiquitin-tagged proteins?
proteasome
81
Staining for vimentin will identify what?
mesenchymal tissue
mesenchymal tumors (sarcoma), but also endometrial carcinoma, RCC, meningioma
82
Staining for desmin will identify what kind of tumor?
muscle tumors like rhabdomyosarcoma
83
Staining for GFAP will identify what tumor types?
neuroglia - astrocytomas and glioblastomas
84
How is cilia structure arranged?
9 doublets and 2 singlets of microtubules
85
In the Na-K pump, what inhibits binding to the K+ site?
ouabain
86
Where is each type of collagen found?
1. MC - bone, skin, tendon, dentin, fascia, cornea, late wound repair
2. cartilage (including hyaline), vitreous body, nucleus pulposus
3. reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue
4. basement membrane, basal lamina, lens
87
What are steps of collagen synthesis?
1. Pro alpha chain backbone (Gly-X-Y)
2. hydroxylation of proline and lysine (requires vit C)
3. glycosylation (triple helix formation)
4. exocytosis
5. cleavage of procollagen C- and N- terminals creating insoluble tropocollagen
6. formation of cross-links (stabilzed by lysyl oxidase)
88
Osteogenesis imperfecta is MC a/w what gene defects?
COL1A1 and COL1A2
89
What gene defects are a/w Ehlers Danlos?
Classic type is collagen V - COL5A1, COL5A2
Vascular type deficient type III collagen
90
X linked recessive CT disorder caused by impaired copper absorption and transport due to defective .... protein (ATP7A)
dx?
what does this result in?
Menkes disease
leads to decreased activity of lysyl oxidase (copper is a necessary cofactor)
results in brittle, "kinky" hair, growth retardation, and hypotonia
91
wrinkles of aging are caused by
decreased collagen and elastin production
92
elastin is rich in
nonhydroxylated proline, glycine, and lysine residues
93
what gives elastin its elastic properties?
cross-linking takes place extracellularly
94
What is the gene defect in Marfan syndrome?
FBN1 gene mutation on chromosome 15 results in defective fibrillin, a glycoprotein that forms a sheath around elastin
95
What are the steps of PCR?
1. denaturation - heated into separate strands
2. annealing - during cooling, excess DNA primers anneal to a specific sequence on each strand to be amplified
3. elongation - heat-stable DNA polymerase replicates the DNA sequence following each primer
96
What is a confirmatory test for HIV after a positive ELISA?
Western blot
97
What kind of lab test is used for work up of hematologic abnormalities and immunodeficiencies?
how is data plotted?
flow cytometry - assess size, granularity, and protein expression (immunophenotype) of individual cells in a sample
plotted as histogram or scatter plot
98
when thousands of nucleic acid sequences are arranged in grids on glass or silicone this is an example of ...
what can this detect?
microarray
detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) for a variety of applications including genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis
99
what is an immunologic test used to detect the presence of either a specific ag or ab?
enzyme-linked immunosorbent assay (ELISA)
100
Describe the karotyping process
metaphase chromosomes are stained, ordered, and numbered according to morphology, size, arm-length ratio, and banding pattern
101
what is FISH lab work used for?
specific localization of genes and direct visualization of chromosomal anomalies at the molecular level
102
What are the steps of cloning?
1. isolate eukaryotic mRNA
2. expose mRNA to RT to produce cDNA (lacks introns)
3. insert cDNA fragments into bacterial plasmids containing abx resistance genes
4. transform recombinant plasmid into bacteria
5. surviving bacteria on abx medium produce cloned DNA (copies of cDNA)
103
Cre-lox system
can inducibly manipulate genes at specific developmental points
104
dsRNA is synthesized that is complementary to the mRNA sequence of interest; when transfected into human cells, dsRNA separates and promotes degradation of target mRNA
what is this called and what will this do?
RNA interference
knocking down gene expression
105
tendency for certain alleles at 2 linked lock to occur together more or less often than expected by chance; measured in population, not family
linkage disequilibrium
106
pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops
loss of heterozygosity (2 hit hypothesis)
107
mutation arises from mitotic errors after fertilization and propagates through multiple tissues or organs
somatic mosaicisim
108
mutations at different loci can produce a similar phenotype
locus heterogneity
109
different mutations in the same locus produce the same phenotype
allelic heterogeneity
110
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
heteroplasmy
111
offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent
uniparental disomy (euploid)
112
What is the difference between heterodisomy and isodoisomy?
heterodisomy indicates a meiosis I error
isodisomy indicates a meisosis II error or postzygotic chromosomal duplication of one pair of chronosomes, and loss of the other of the original pair
113
What am I considering when I find a recessive disorder when only one parent is a carrier?
uniparental disomy
114
hardy-weinberg law assumptions
1. no mutation occurring at the locus
2. natural selection is not occurring
3. completely random mating
4. no net migration
115
due to defects in structural genes; many generations, males and females affected
autosomal dominant
116
often due to enzyme deficiencies; usually only seen in one generation
autosomal recessive
117
sons of heterozygous mothers have 50% chance of being affected;
x linked recessive
118
transmitted through both parents; mothers transmit to 50% of daughters and sons; fathers transmit to all daughters but no sons
X linked dominant
119
transmitted only through the mother; all offspring of affected females may show signs of disease
mitochondrial inheritance
120
female carriers variably affected depending on the pattern of inactivation of the X chromosome carrying the mutant v normal gene
lyonization
121
X linked recessive disorders
Oblivious Female Will Often Give Her Boys Her x-Linked Disorders
* Ornithine transcarbamylase deficiency
* Fabry disease
* Wiskott-Aldrich syndrome
* Ocular albinism
* G6pD deficiency
* Hunter syndrome
* Bruton agammaglobulinemia
* Hemophilia A and B
* Lesch-Nyhan syndrome
* Duchenne and Becker MD
122
autosomal dominant; CTG trinucleotide repeat expansion in the DMPK gene
dx?
what is abnormally expressed?
ssx?
Myotonic type 1 Muscular Dystrophy
abnormal expression of myotonin protein kinase
myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia
123
trinucleotide repeat in FMR1 gene (CGG) - dx?
inheritance pattern?
what does this repeat cause?
Fragile X syndrome
X linked dominant
hypermethylation and decreased expressivity
124
What are 4 trinucleotide repeat expansion diseases?
Huntington disease (CAG)
Myotonic dystrophy (CTG)
Fragile X syndrome (CGG)
Friedreich Ataxia (GAA)
125
What does the first trimester US show for Down Syndrome?
increased nuchal translucency and hypoplastic nasal bone; decreased serum PAPP-A, increased beta-hCG
126
What does second trimester quad screen for Down Syndrome show?
decreased AFP, increased b-hCG, decreased estriol, increased inhibin A
127
What screening tests do you find positive with trisomy 18?
PAPP-A and free b-hCG are decreased in first tri
quad screen shows decreased AFP, decreased b-hCG, decreased estriol and normal or decreased inhibin A
128
chromosome 3
von Hippel Lindau, RCC
129
chromosome 4
ADPKD (PKD2), achondroplasia, Huntingtons
130
chromosome 5
cri-du-chat, FAP
131
chromosome 6
hemochromatosis (HFE)
132
chromosome 7
Williams syndrome, CF
133
chromosome 9
Friedreich ataxia
134
chromosome 11
Wilms tumor, beta-globin gene defects (SCD, b-thalassemia, MEN1)
135
chromosome 13
Patau, Wilson Disease, retinoblastoma (RB1), BRCA2
136
chromosome 15
Prader Willi, Angelman, Marfan
137
chromosome 16
ADPKD (PKD1), alpha-globin gene defects (a-thalassemia)
138
chromosome 17
NF type 1, BRCA1, p53
139
chromosome 18
Edward syndrome
140
chromosome 22
NF type 2, DiGeorge
141
chromosome X
Fragile X, X-linked agammaglobulinemia, Klinefelter syndrome
142
when the long arms of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost - what is this called and what chromosome pairs are normally invovled?
Robertsonian translocation
13, 14, 15, 21, 22
143
congenital microdeletion of long arm chromosome 7 (deleted region includes elastin gene)
Williams syndrome
144
DiGeorge presentation can be due to
aberrant development of 3rd and 4th branchial pouches
145
What vitamin is important for differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells)?
vitamin A (retinol)
146
tx for acute promyelocytic leukemia
all-trans retinoic acid
147
what happens in Vit A deficiency?
night blindness, dry scaly skin, corneal degeneration, bitot spots on conjunctiva, immunosuppression
148
What reactions is thiamine (thiamine pyrophosphate) a cofactor for?
* pyruvate dehydrogenase (links glycolysis to TCA cycle)
* alpha-ketoglutarate dehydrogenase (TCA cycle)
* transketolase (HMP Shunt)
* branched-chain ketoacid dehydrogenase
149
How do you dx vit B1 deficiency?
dx made by increase in RBC transketolase activity following Vit B1 administration
150
component of flavins FAD and FMN, used in cofactors in redox reactions, eg the succinate dehydrogenase reaction in TCA cycle
Vit B2/riboflavin
151
deficiency of vit B2 presents as
cheilosis and corneal vascularization
152
used to tx dyslipidemia; lowers VLDL and raises HDL
what is this derived from?
B3/niacin
tryptophan
153
autosomal recessive deficiency of neutral amino acid transporters in proximal renal tubular cells and on enterocytes
hartnup disease
154
essential component of CoA, a cofactor for acyl transfers, and fatty acid synthase
Vit B5 (pantothenic acid)
155
responsible for synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epi, NE, DA, and GABA
Vit B6 pyridoxine
156
deficiency of vit B6 will cause
convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
157
Vit B7/biotin is a cofactor for carboxylation enzymes in what reactions?
* pyruvate carboxylase
* pyruvate to oxaloacetate
* acetyl-CoA carboxylase
* acetyl CoA to malonyl CoA
* propionyl CoA carboxylase
* propionyl CoA to methylmalonyl CoA
158
Where is vit B9 absorbed?
Labs with B9 deficiency show...
absorbed in jejunum
increased homocysteine, normal methylmalonic acid levels
159
folate deficiency can be caused by what drugs?
phenytoin, sulfonamides, methotrexate
160
what is a cofactor for methionine synthesis?
cobalamin (Vit B12)
161
What is the CNS damage a/w B12 deficiency?
paresthesias and subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin
162
Labs a/w B12/cobalamin deficiency?
increased serum homocysteine and methylmalonic acid levels, and secondary folate deficiency
163
What does Vit C do?
* antioxidant
* facilitates iron absorption by reducing it to Fe2+ state
* necessary for hydroxylation of proline and lysine in collagen synthesis
* necessary for dopamine beta-hydroxylase, which converts dopamine to NE
164
What vitamin should purely breastfed infants also get?
vitamin D
165
increase activation of Vit D by epithelioid macrophages is seen in what disease?
granulomatous disease
166
What is the name for vit E?
tocopherol/tocotrienol
167
Vit E deficiency will present with?
* hemolytic anemia
* acanthocytosis
* muscle weakness
* posterior column and spinocerebellar tract demyelination
168
how can you differentiate deficiency of B12 from Vit E when they both have neuro ssx';
E deficiency wont have megaloblastic anemia, hypersegmented neutrophils, or increased serum methylmalonic acid levels
169
high dose supplementation of vit E may alter
metabolism of vit K - causing enhanced anticoagulant effects of warfarin
170
What are the names for vitamin K?
phytomenadione, phylloquinone, phytonadione
171
deficiency of vit K will present with
neonatal hemorrhage with increased PT and aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vit K)
172
zinc deficiency presents with
* delayed wound healing, hypogonadism, decreased adult hair, dysgeusia, anosmia, acrodermatitis enteropathica
173
What is the difference between Kwashiorkor and marasmus?
* Kwashiorkor
* protein malnutrition
* skin lesions, edema due to decreased oncotic pressure, liver malfunction (fatty change d/t decrease apolipoprotein synthesis
* Marasmus
* malnutrition not causing edema
* deficient calories but no nutrients are entirely absent
* muscle wasting
174
What is the limiting reagent in ethanol metabolism?
Alcohol dehydrogenase operates with what order of kinetics?
NAD+
zero order kinetics
175
ethanol metabolism increases NADH/NAD+ ratio in the liver causing what to happen?
* pyruvate to lactate
* lactic acidosis
* oxaloacetate to malate
* prevents gluconeogenesis leading to fasting hypoglycemia
* dihydroxyacetone phosphate to glycerol-3-phosphate
* combines with fatty acids to make triglycerides leading to hepatosteatosis
chronic alcoholism
176
What metabolic pathways happen both in the mitochondria and the cytosol?
* heme synthesis
* urea cycle
* gluconeogenesis
(HUGs take two)
177
What metabolic pathways happen in the mitochondria?
* fatty acid oxidation (beta ox)
* acetyl-CoA production
* TCA cycle
* oxidative phosphorylation
* ketogenesis
178
rate determining enzymes of glycolysis, gluconeogenesis, TCA cycle, glycogenesis, glycogenolysis
* glycolysis - PFK1
* gluconeogenesis - fructose-1,6-bisphosphatase
* TCA cycle - isocitrate dehydrogenase
* glycogenesis - glycogen synthase
* glycogenolysis - glycogen phosphorylase
179
ATP production is most efficient aerobically with what shuttles?
32 net ATP via malate-asparate shuttle (heart and liver)
30 net ATP via glycerol-3-phosphate shuttle (muscle)
180
What are universal electron acceptors? are they used in catabolic or anabolic processes?
Nicotinamides (NAD+ from vit B3, NADP+) and flavin nucleotides (FAD+ from B2)
NAD+ is usually in catabolic processes and NADPH is used in anabolic processes (steroid and FA synthesis)
181
NADPH is a product of what metabolic pathway and is used for...
HMP shunt
* used for
* anabolic processes
* respiratory burst
* cytochrome P450
* glutathione reductase
182
What is the difference between hexokinase and glucokinase?
* hexokinase
* most tissues, except liver and pancreatic beta cells
* not induced by insulin
* feedback inhibited by Glucose-6-phosphate
* glucokinase
* liver and beta cells
* induced by insulin
* no feedback inhibited by glucose-6-phosphate
183
regulation by fructose-2,6-bisphosphate in the fasting state
* increased glucagon
* increases cAMP
* increases PKA
* increases FBPase2 and decreases PFK2
* less glycolysis
* more gluconeogenesis
184
regulation by fructose-2,6-bisphosphate in the fed state
* increased insulin
* decreases cAMP
* decreases PKA
* decreases FBPase2 and increases PFK2
* more glycolysis
* less gluconeogenesis
185
what is the mitochondrial enzyme complex linking glycolysis and TCA cycle?
When is it active?
pyruvate dehydrogenase complex
active in fed state
186
The 3 enzymes in the pyruvate dehydrogenase complex require what 5 cofactors?
1. Thiamine pyrophosphate (B1)
2. lipoic acid
3. CoA (B5, pantothenic acid)
4. FAD (B2 riboflavin)
5. NAD+ (B3 niacin)
187
vomiting, rice-water stools, garlic breath, QT prolongation - poisoned by what?
arsenic poisoning
inhibits lipoic acid
188
what results if there is a deficiency in pyruvate dehydrogenase pathway?
buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT)
neuro deficits, lactic acidosis, increased serum alanine starting in infancy
189
what complex requires the same 5 cofactors as the pyruvate dehydrogenase complex?
alpha-ketoglutarate dehydrogenase complex
190
What are the products of the TCA cycle?
3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/acetyl-CoA
(2x everything per glucose)
191
NADH electrons from glycolysis enter mitochondria via
the malate-aspartate or glycerol-3-phosphate shuttle
192
What substances directly inhibit electron transport? Where do they act?
* rotenone - complex I inhibitor
* antimycin A - complex III inhibitor
* CO, cyanide - complex IV inhibitor
193
What is an ATP synthase inhibitor? what happens?
oligomycin
directly inhibits mitochondrial ATP synthase, causing an increased proton gradient
no ATP produced
194
What agents do uncoupling of the ETC, increasing permeability, causing a decreased proton gradient and increased O2 consumption?
What else does this do?
2,4-dinitrophenol (used illicityly for wt loss)
aspirin (fevers occur s/p OD)
thermogenin in brown fat
ATP synthesis stops, but ETC continues; produces heat
195
What are the irreversible enzymes in gluconeogenesis?
* pyruvate carboxylase
* phosphoenolpyruvate carboxykinase
* fructose-1,6-bisphosphatase
* glucose-6-phosphatase
196
essential fructosuria is a benign condition with what defect?
defect in fructokinase
197
hereditary deficiency of aldolase B
fructose intolerance
198
symptoms following consumption of fruit, juice or honey, presenting with hypoglycemia, jaundice, cirrhosis, and vomiting
dx?
tx?
fructose intolerance
decrease intake of both fructose and sucrose (glucose+fructose)
199
What metabolic pathways are inhibited in fructose intolerance?
glycogenolysis and gluconeogenesis
200
galactose is appearing in blood and urine; infantile cataracts; may present as failure to track objects or to develop a social smile
dx?
what accumulates?
galactokinase deficiency
galactitol accumulates if galactose is present in diet; mild condition
201
in Classic Galactosemia there is an absence of ...
this causes damge by...
can predispose to what...
galactose-1-phosphate uridyltransferase
accumulation of toxic substances (including galactitol which accumulates in the lens of the eye)
E. coli sepsis in neonates
202
What enzyme changes glucose to sorbitol?
Sorbitol can accumulate if there is not this enzyme in the tissues..
What tissues don't have this enzyme?
aldose reductase
sorbitol dehydrogenase (converts to fructose)
lens (mix), retina, kidneys, and schwann cells have only aldose reductase
203
What does stool and breath show with lactase deficiency?
stool shows decreased pH and breath shows increased H+ content with lactose hydrogen breath test
204
What are the basic amino acids?
His, lys, arg
Arg most basic
His has no charge at body pH
205
What are the glucogenic amino acids?
methionine, histidine, and valine
206
What does the urea cycle do?
excess nitrogen is converted to urea and excreted by the kidneys
207
urea cycle steps/enzymes
* N-acetylglutamate is the allosteric activator of carbamoyl phosphate synthetase I
* creates carbamoyl phosphate
* ornithine transcarbamylase
* citrulline
* argininosuccinate synthetase plus Aspartate and ATP
* argininosuccinate
* argininosuccinase
* arginine (and fumarate goes away)
* arginase and water
* urea to kidney and ornithine back to cycle
208
hyperammonemia results in what substances being depleted?
excess NH3, depleting alpha-ketoglutarate, leading to inhibition of TCA cycle
209
what is the MC urea cycle disorder?
what happens?
ornithine transcarbamylase deficiency - X linked recessive (other urea cycle issues are autosomal recessive)
excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)
210
increased orotic acid in blood and urine would lead me to think of...
what else do I see on labs?
ornithine transcarbamylase deficiency
also find decreased BUN, symptoms of hyperammonemia; no megaloblastic anemia (v orotic aciduria)
211
PKU is due to...
decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin (BH4) cofactor
212
tx of PKU
decrease phenylalanine and increase tyrosine in diet, tetrahydrobiopterin supplementation
213
blocked degradation of branched amino acids (isoleucine, leucine, valine) due to decreased branched-chain alpha-katoacid dehydrogenase
dx and tx
maple syrup urine disease
restriction of leucine, isoleucine, and valine in diet, supplement with thiamine
214
congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
dx?
what does this cause?
alkaptonuria
pigment-forming homogentisic acid accumulates in tissue
usually benign - bluish black CT, ear cartilage, and sclerae; urine turns black on prolonged exposure to air; may have debilitating arthralgias
215
What do all of these cause? - cystathionine synthase deficiency; decreased affinity of cystathionine synthase for pyridoxal phosphate; methionine synthase deficiency
homocystinuria
* increase homocysteine in urine
* osteoporosis
* marfanoid habitus
* ocular changes
* cardiovascular effects
* kyphosis
* intellectual disability
216
What is the diagnostic test for cystinuria?
urinary cyanide-nitroprusside test
217
cystinuria is a hereditary defect of renal PCT and intestinal aa transporter that prevents reabsorption of...
what shape are cystine stones?
cystine, ornithine, lysine, and arginine
hexagonal
218
tx of cystinuria?
urinary alkalinization (K+ citrate, acetozolamide) and chelating agents (penicillamine) increase solubility of cystine stones; good hydration
219
What is the deficient enzyme and what is accumulated in Tay Sachs?
deficient: hexosaminidase A
accumulate GM2 ganglioside
220
What is the deficient enzyme and what is accumulated in Fabry disease?
deficient alpha-galactosidase A
accumulate ceramide trihexoside
221
What is the deficient enzyme and what is accumulated in metachromatic leukodystrophy?
deficient arylsulfatase A
accumulate cerebroside sulfate
222
What is the deficient enzyme and what is accumulated in Krabbe disease?
deficient galactocerebrosidase
accumulate galactocerebroside, psychosine
223
What is the deficient enzyme and what is accumulated in Gaucher disease?
deficient in glucocerebrosidase (beta-glucosidase)
accumulate glucocerebroside
224
hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of the femur, bone crises, and lipid laden macrophages resembling crumpled tissue paper
Gaucher disease
225
What is the deficient enzyme and what is accumulated in Niemann-Pick disease?
deficient sphingomyelinase
accumulate sphingomyelin
226
DD, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
dx?
what is deficient and what accumulates?
Hurler syndrome
deficient alpha-L-iduronidase
accumulate heparan sulfate and dermatan sulfate
227
Mild hurler syndrome plus aggressive behavior and no corneal clouding
Hunter syndrome
deficient iduronate sulfatase
accumulate heparan sulfate and dermatan sulfate
228
What shuttles are used in fatty acid metabolism?
citrate shuttle in fatty acid synthesis
carnitine shuttle in fatty acid degradation
229
degradation of TGs circulating in chylomicrons and VLDLs; found on vascular endothelial surface
lipoprotein lipase (LPL)
230
degradation of TGs remaining in IDL
hepatic TG lipase
231
what catalyzes esterification of 2/3 of plasma cholesterol
LCAT
232
How is LDL taken up?
taken up by target cells via receptor-mediated endocytosis
233
HDL acts as a repository for
apolipoproteins C and E
234
AR, chylomicrons, LDL, and VLDL absent; deficiency in apoB48 and apoB100
abetalipoproteinemia
235
lipoprotein lipase or apoCII deficiency
dx
what will be in blood?
Type I familial dyslipidemia - hyperchylomicronemia
chylomicrons, TG, cholesterol increased
236
defective apoE and increased chylomicrons and VLDL in blood
Dysbetalipoproteinemia/Type III
237
hepatic overproduction of VLDL
hypertriglyceridemia (type IV)
