Biochemistry Flashcards
(197 cards)
1
Q
Chromatin Structure
A
H1 bind to nucleosome and to linker DNA –> stabilize chromatin fiber.
(-) phosphate
(+) lysine and arginine
2
Q
Heterochromatin
A
Condensed, transcriptionally inactive
increased methylation
decreased acetylation
ex. Barr bodies
3
Q
Euchromatin
A
less condensed, transcriptionally active
4
Q
Histone Methylation
A
reversible transcription suppression usually
5
Q
Histone Acetylation
A
remove histone (+) charge –> relaxed DNA coiling –> increase transription
6
Q
Histone deactylation
A
remove acetyl groups –> tighten DNA –> decrease transcription
7
Q
Deamination reactions
A
Cytosine –> uracil
Adenine –> hypoxanthine
Guanine –> xanthine
5- methylcytosine –> thymine
8
Q
Amino acids in purine synthesis
A
glycine
aspartate
glutamine
9
Q
Pyrimidine synthesis drugs
A
Leflunomide (inhibit dihydroorotate dehydrogenase)
5-FU and capecitabine (inhibit thymidine synthase via increase 5F-dUMP
10
Q
Purine Synthesis drugs
A
6-MP and azathioprine (inhibit de novo purine synthesis)
Mycophenolate and ribavirin (inhibit inosine monophosphate dehydrogenase)
11
Q
Purine and Pyrimidine synthesis drugs
A
Hydroxyurea (inhibit ribonucleotide reductase)
methotrexate (human), trimethoprim (bacteria), pyrimethamine(protozoa) (inhibit DHR reductase)
12
Q
Adenosine deaminase deficiency
A
degrade adenosine and deoxyadenosine
decreased ADA –> increased dATP –> decrease ribonucleotide reductase activity –> lymphotoxicity
AR SCID
13
Q
Lesch Nyhan Syndrome
A
X linked Recessive
absent HGPRT (convert hypoxanthine to IMP and guanine to GMP) excess uric acid production and de novo purine synthesis.
Disability self mutilation, aggression, hyperuricemia, gout, dystonia
T(x) allopurinol or febuxstat
14
Q
Origin of replication
A
TATA box
15
Q
Helicase
A
unwind DNA
Deficient: BLOOM syndrome (BLM gene mut.)
16
Q
DNA topoisomerase
A
create single or double stranded break in helix to add or remove supercoils
Eukaryotes- irinotecan inhibit TOP 1, etoposide inhibit TOP 2
Prokaryotes- fluoroquinolones inhibit TOP 2 and 4
17
Q
DNA polymerase 3
A
Prokaryotes only. DNA poly 3 is 5 –> 3 synthesis. Drugs blocking DNA replication have a modified 3’OH –> chain termination.
18
Q
DNA polymerase 1
A
Prokaryotes only. excise RNA primer in 5 –>3 direction
19
Q
Telomerase
A
Eukaryotes only. Reverse transcriptase thats adds TTAGGG to 3’ end. Dysregulation –> cancer
20
Q
Lac operon
A
E.coli
glucose is absent and lactose is present –> activation for lactose metabolism.
low glucose –> increase adenylate cyclase –> increase cAMP –> activate CAP –> increase transcription
High lactose –> unbinds repressor protein –> increase transcription
21
Q
Nucleotide excision repair
A
Single Strand
endocuclease cut damaged DNA. DNA pol and ligase fill. G1 phase.
Defect: xeroderma pigmentosum (inability to repair DNA pyrimidine dimers caused by UV) –> dry skin, light sensitivity, skin cancer
22
Q
Base excision repair
A
Single Strand
Glycosylase removes altered base and creates AP side. Nucleotides removed by AP- endonuclease/lyase. DNA pol and ligase fill gaps.
Spontaneous or toxic deamination
23
Q
Mismatch repair
A
Single Strand
S phase
Defective: Lynch syndrome (HNPCC)
24
Q
Nonhomologous End joining
A
Double strand
Brings together 2 ends of DNA fragments. Lost DNA
Defect: Ataxia Telangiectasia
25
Homologous End Joining
Double Strand
2 homologous DNA duplexes. No lost DNA
Defect: BRCA1 and Fanconi anemia
26
Promoter
Site where RNA pol 2 and transcription factors bind to DNA upstream from gene locus. Mutation --> dramatic decrease in gene transcription
27
Enhancer and Silencer
located close to or far from or within gene.
28
RNA processing
1. 5' cap (7 methylguanosine)
2. polyadenylation 3'
3. splice out introns
29
Eukaryote RNA pol
1- makes rRNA
2- makes mRNA, miRNA, snRNA, open DNA at promoter site.
3- tRNA
a-amanitin (cap mushrooms) inhibit RNA pol 2 --> hepatotoxicity
Actinomycin D- inhibit RNA pol in pro and eukaryotes
30
Prokaryote RNA pol
1 RNA pol makes all RNA
| Rifampin inhibit DNA dependent RNA pol in prokaryotes
31
snRNP defect
Spinal Muscular Atrophy (decreased SMN protein) --> congenital degeneration of anterior horns of spinal cord --> symmetric weakness (floppy baby)
32
tRNA structure
CCA on 3' end carry amino acid
T-arm - tRNA ribosome binding
D- arm- allow detection by aminoacyl tRNA synthetase
33
tRNA charging
aminoacyl tRNA synthetase binds charged tRNA to the codon.
34
Initiation Protein Synthesis
1. eukaryotic initiation factors identify 5'cap
2. assemble the 40S ribosomal subunit with the initiatory tRNA
3. released when the mRNA and the ribosomal 60S subunit assemble with the complex (requires GTP)
35
Elongation Protein Synthesis
1. Aminoacyl tRNA synthetase binds to A site (require elongation factor and GTP)
2. rRNA catalyze 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
36
Termination Protein Synthesis
Eukaryotic release factors recognize the stop codon and halt translation --> completed polypeptide is released from ribosome. (requires GTP)
37
CDK
constitutively expressed but inactive when not bound to cyclin
38
cyclin
regulatory proteins that control cell cycle events; phase specific, activate CDKs
39
Cycin-CDK
phosphorylate other proteins to coordinate cell cycle progression; must be activated and inactivated at appropriate times for cell cycle progress
40
Tumor suppressors
p53 --> induce p21 --> inhibit CDK --> Rb hypophosphorylate (activate) --> inhibit G1S
Mut --> Li Fraumeni
Growth factors bind TK receptors to transition the cell from G1 --> S
41
Rough ER
synthesis of exported proteins and N-linked oligosaccharide addition to lysosomal and other proteins
Nissl bodies- synthesize peptide neurotransmitters for secretion
Free ribosomes- unattached to any membrane are site of synthesis of cytosolic, peroxisomal and mitochondrial proteins
42
Smooth ER
site of steroid synthesis and detox of drugs and poisons. Glucose 6 phosphatase.
Liver, hepatocytes and adrenal cortex and gonads
43
Golgi
distribution center
N oligosaccharides on Asparagine
O oligosaccharides on serine and threonine
Mannose 6 Phosphate to lysosome.
44
I cell Disease
inherited lysosomal storage disease (AR)
Defect in NAP --> failure of golgi to phosphorylate mannose residues --> proteins are secreted extracellularly rather than delivered to golgi. --> coarse facial features, gingival hyperplasia, clouded cornea, restricted joint movement, claw hand, high plasma lysosomal enzymes.
FATAL at childhood
45
Dysfunctional Signal recognition proteins
accumulation of protein in cytosol
46
Vesicular trafficking proteins
COPI: golgi --> golgi --> ER
COPII: golgi forward
Clathrin: golgi--> lysosomes, PM --> endosomes
47
Peroxisome
B oxidation of VLCFA
a oxidation of branched FA
catabolism of amino acids and ethanol
synthesis of cholesterol, bile acids and plasmalogens
48
Zellweger Syndrome
AR
mut PEX (peroxisome biogenesis)
Hypotonia, seizures, hepatomegaly, early death
49
Refsum Disease
AR a oxidation
phytanic acid not metabolized to pristanic acid.
Scaly skin, ataxia, cataracts, shortening of 4th toe, epiphyseal dysplasia
T(x): diet, plasmapheresis.
50
Adrenoleukodystrophy
X linked Recessive B oxidation
ABCD1 mut --> VLCFA buildup in adrenal glands, white matter of brain, testes,
Adrenal gland crisis, coma, death
51
Microfilaments
Muscle contraction, cytokinesis (actin, microvilli)
52
Intermediate Filaments
Maintain cell structure (vimentin, desmin, cytokeratin, lamins, GFAP, neurofilament)
53
Microtubules
Movement and cell division (cilia, mitotic spindle, axonal trafficking, centrioles)
Retrograde (Dyenin)
Anterograde (kinesin)
C. tetani, HSV, polio, rabies use dyenin
Drugs: mebendazole, griseofulvin, colchicine, Vincristine, Paclitaxel
54
Cilia Structure
9 doublet + 2 singlet
55
Kartagener Syndrome
AR
immotile cilia due to dyenin arm defect.
decrease male and female fertility due to immotile sperm and dysfunctional fallopian tube cilia. Increased risk of ectopic pregnancy. Can cause bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss and situs inversus.
Screening: decreased NO nasal
56
Na+/K+ ATPase
each ATP --> 3 Na+ leave cell, 2K+ enter cell
Ouabin inhibit binding to K+ site
Cardiac glycosides (digoxin) inhibit Na+/K= ATPase --> inhibit Na+/Ca2+ exchange --> increase Ca2+ --> increase cardiac contractility
57
Type 1 Collagen
Bone, Skin, Tendon
| Decrease in osteogenesis Imperfecta
58
Type 2 Collagen
Cartilage
59
Type 3 Collagen
Reticulin (blood vessels)
| Defect- vascular type ehlers Danlos
60
Type 4 Collagen
Basement Membrane
| Defect: alport syndrome and targeted by autoantibodies in Goodpasture syndrome
61
Collagen Synthesis
1. Synthesis- translation of collagen a chains (1/3 glycine)
2. Hydroxylation- proline and lysine residues (requires vitamin C)
3. Glycosylation- a chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds. (defect osteogenesis imperfecta)
4. Exocytosis into extracellular space
5. Proteolytic processing- cleave disulfide rich terminal regions of procollagen --> insoluble tropocollagen
6. cross linking- covalent lysine- hyrdoxylysine --> collagen fibrils (defect: Menkes Disease)
62
Osteogenesis Imperfecta
AD
Defect COL1A1 and COL1A2
Multiple fractures and bone deformities after minimal trauma, blue sclera, tooth abnormalities, conductive hearing loss.
63
Ehlers Danlos
Faulty collagen causing hyperextensible skin, hypermobile joints and tendency to bleed.
Classical: COL5A1/5A2- joint and skin
Vascular- COL3A1- fragile tissues including vessels.
64
Menkes Disease
X linked recessive
impaired copper absorption and transport (ATP7A).
Lower copper levels --> decrease activity of lysyl oxidase --> defective collagen
Brittle, kinky hair, growth retardation, hypotonia, increase risk of cerebral aneurysms
65
Elastin
stretchy protein in skin, lungs, large arteries, elastic ligaments, vocal cords. Rich in nonhydroxylated proline, glycine and lysine.
a1 antitrypsin inhibits breakdown
66
Marfan Syndrome
AD (FBN1 gene mutation on Chromosome 15)
tall with long extremities, pectus carinatum or excavatum. hypermobile joints, long tapering fingers and toes, cystic medial necrosis of aorta, aortic aneurysm, rupture or dissection. mitral valve prolapse. Subluxation of lenses
67
PCR
Amplify DNA
1. Denature (95C)
2. Anneal (55C)
3. Elongate (72C)
68
rtPCR
detect mRNA. uses reverse transcription to create complimentary DNA template.
69
CRISPR
genome editing. guide RNA complimentary to target DNA and Cas9 endonuclease makes break at target site. Break is repaired by NHEJ --> frameshift mutation (knock out)
70
Southern Blot
DNA cleaved and electrophoresis
radiolabeled DNA probe
Film
71
Northern Blot
RNA sample
72
Western Blot
Protein sample
73
Southwestern Blot
DNA binding protein
74
Flow Cytometry
assess size, granularity and protein expression of individual cells in a sample.
Cells tagged with Ab
Workup for hematologic abnormalities
75
Microarrays
nucleic acid on grid. DNA or RNA probe hybridized to the chip and scanner detects the relative amounts of complimentary binding.
profile gene expression levels of thousands of genes simultaneously.
Detect SNPs and CNVs
76
Enzyme linked immunosorbent assay
detect presence of specific Ag or Ab in patient blood sample. Substrate reacts with enzyme --> detectable signal.
77
Karyotyping
Colchicine is added to cell. Chromosomes stained, ordered and numbered according to morphology.
Performed on blood, cone marrow, amniotic fluid or placental tissue.
78
Fluorescence in sity hybridization
Fluorescent DNA/ RNA probe binds to specific gene site of interest on chromosomes.
Specific localization of genes and direct visualization of chromosomal anomalies at molecular level
79
Molecular cloning
Production of recombinant DNA molecule in a bacterial host
80
Cre-Lox
inducibly manipulate genes at specific developmental points
81
miRNA
naturally produced by the cell as hairpin structures. Block translation and accelerating mRNA degradation.
82
siRNA
derived from exogenous dsRNA. Requires complete nucleotide pairing --> highly specific mRNA targeting --> mRNA cleavage prior to translation
KNOCK DOWN
83
Hardy Weinberg
p+q=1
p^2 + 2pq +q^2 = 1
if no mutations at locus, no natural selection, random mating, no migration, large population.
84
Prader Willi Syndrome
IMPRINTING Chromosome 15 Paternal
Maternally derived genes are silenced. Disease occurs when the paternal allele is deleted.
Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia.
85
AngelMan Syndrome
IMPRINTING Maternal UBE3A Chromosome 15
Paternally derived UBE3A is silenced. Disease occurs when the maternal allele is deleted.
Seizures, ataxia, intellectual disability, inappropriate laughter.
86
Cystic Fibrosis
AR defect in CFTR on Chromosome 7 (del Phe508)
White
mut. ATP gated Cl- channels (retained in RER) --> decreased Cl- secretion and increase Cl- intracellularly --> Na+ reabsorption via ENaC --> increase H2O reabsorption --> abnormally thick mucus secreted into lungs and GI tract.
Increased Cl- in sweat.
Recurrent pulm infection, pancreatic insufficiency (steatorrhea, meconium ileus), infertility in men, Nasal polyps, clubbing of nails.
T(x): saline, albuterol, pancreatic enzyme replacement.
87
Duchenne
```
X linked (frameshift deletion or nonsense) DMD gene
Weakness in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle.
Gowers sign (use arms to help stand up)
Increase CK and aldolase
```
88
Becker
X linked non frameshift deletion of DMD gene
89
Myotonic Dystrophy
AD CTG repeats in DMPK gene --> abnormal myotonin protein kinase --> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia.
90
Rett Syndrome
sporadic Women 1-4 years
de novo mut MECP2 on X chromosome
regression in motor, verbal, and cognitive abilities, ataxia, seizures, growth failure, and hand wringing.
91
Fragile X
X linked Dominant CGG repeat in FMR1 gene --> hypermethylation --> decreased expression.
Post pubertal macroorchidism, long face with large jaw, large ears, autism, mitral valve prolapse, hypermobile joints
92
Down Syndrome
Trisomy 21
intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, duodenal atresia, Hirschsprung disease, ASD, early Alzheimers, increased risk of AML/ALL
Increased hCG and inhibin
Advanced maternal age
93
Edwards Syndrome
Trisomy 18
prominent occiput, rocker bottom feet, intellectual disability, nondisjunction, clenched fists with overlapping fingers, low ears, congenital heart disease, omphalocoele.
Death by 1 year
94
Patau Syndrome
Trisomy 13
Intellectual disability, rocker bottom feet, micropthalmia, microencephaly, cleft lip, holoprosencephaly, polydactyly, congenital heart disease, PCKD.
Death by 1 year
95
Cri du chat Syndrome
congenital deletion on short arm Chromosome 5 (46 XX/XY)
| microencephaly, moderate to severe intellectual disability, high pitched crying, epicanthal folds, VSD
96
Williams Syndrome
congenital microdeletion of long arm of chromosome 7 (elastin gene)
elfin facies, intellectual disability, hypercalcemia, good verbal skills, extremely friendly with strangers, supravalvular aortic stenosis, renal artery stenosis.
97
Vitamin A
Antioxidant, visual pigments, treat measles and APML.
In liver and leafy vegetables.
Deficiency: night blindness, bitot spots, corneal degeneration, immunosuppression
Excess: acute tox (nausea, vomiting, vertigo and blurred vision. Chronic tox (alopecia, dry skin, hepatic tox, HTN.
Teratogenic (cleft palate, cardiac abnormalities.
Contra in pregnancy!
98
B1 (thiamine)
cofactor for branched chain ketoacid dehydrogenase, a ketoglutarate dehydrogenase, Pyruvate dehydrogenase, transketolase.
Deficiency: Beriberi, wernicke encephalopathy, Korsakoff
impaired glucose breakdown --> ATP depletion worsened by glucose infusion.
D(x) high RBC transketolase activity following B1 administration
99
B2 (Riboflavin)
component of FAD and FMN (succinate dehydrogenase)
| Deficiency: cheilosis, corneal vascularization
100
B3 (niacin)
NAD+ and NADP+. Derived from tryptophan. Treat dyslipidemia, low VLDL and raise HDL.
Deficiency: Glossitis, pellagra (Diarrhea, dementia, dermatitis)
Excess: facial flushing, hyperglycemia, hyperuricemia.
101
Hartnup
AR Deficiency in Tryptophan transporter in proximal renal tubular cells on enterocytes --> neutral aminoaciduria and decrease absorption from the guy --> decreased tryptophan for conversion to niacin --> pellagra
T(x): high protein diet and nicotinic acid.
102
B6 (Pyridoxine)
Cofactor for transamination, decarboxylation reactions, glycogen phosphorylase, synthesis of neurotransmitters.
Deficiency: convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia
103
B5 (Pantothenic acid)
Coenzyme A and fatty acid synthase
| Deficiency: Dermatitis, enteritis, alopecia, adrenal insufficiency.
104
B7 (biotin)
carboxylation enzymes
Deficiency: Dermatitis, enteritis, alopecia. Caused by long term antibiotic use or excessive ingestion of raw egg whites.
105
B9 (folate)
Coenzyme for 1-carbon transfer/methylation reactions. DNA and RNA synthesis
Deficiency: Macrocytic, megaloblastic anemia, hypersegmented PMN, glossitis, no neuro symptoms. Caused by phenytoin, sulfonamides, MTX.
D(x): high homocysteine, normal methylmalonic acid (alcoholism and pregnancy)
106
B12 (cobalamin)
Cofactor for methionine synthase and methylmalonyl CoA mutase, DNA synthesis.
Deficiency: Macrocytic, megaloblastic anemia, hypersegmented PMNs, paresthesias and combined degeration due to abnormal myelin. Caused by malabsorption (D. latum), achlorydia, bacterial overgrowth, alcohol, lack of intrinsic factor, no terminal ileum, drugs.
D(x): increase homocysteine and methylmalonic acid.
107
C (ascorbic acid)
antioxidant, iron absorption, hydroxylation of proline and lysine in collagen synthesis, DA B hydroxylase.
Deficient: scurvy (swollen gums, easy bruising, petechiae, hemarthrosis, anemia, poor wound healing.
Excess: nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis.
108
D
Increase intestinal absorption of Ca2+ and PO4. increase bone mineralization at low levels, increase resorption at higher levels.
Regulated by increase PTH, decrease Ca2+ and PO4 --> increase 1, 25 OHD3 (inhibits itself)
Deficient: Rickets (kids, osteomalacia (adults)
Excess: hypercalcemia, hypercaliuria, loss of appetite, stupor.
109
E (tocopherol, tocotrienol)
Antioxidant (protect RBC from radical damage)
Deficient: hemolytic anemia, acanthocytosis, muscle weakness, demyelination of posterior columns
Excess: enterocolitis in infants.
110
K
Activated by epoxide reductase --> blood clotting (2, 7, 9, 10).
Deficiency: neonatal hemorrhage with increased PT and PTT but normal bleeding time.
NOT IN BREAST MILK
111
Zinc
zinc fingers and cofactor
deficiency: delayed wound healing, suppressed immunity, male hypogonadism, decreased adult hair. Associated with acrodermatitis enteropathica,
112
Kwashiorkor
protein malnutrition
| skin lesions, edema due to decreased plasma oncotic pressure, liver malfunction (swollen abdomen)
113
Marasmus
malnutrition not causing edema. Diet is deficient in calories but no nutrients are entirely absent.
114
Fomepizole
block alcohol dehydrogenase
| Antidote for overdoses of methanol or ethylene glycol
115
Disulfram
blocks acetaldehyde dehydrogenase --> increase acetaldehyde --> increase hangover symptoms --> discourage drinking.
116
Ethanol metabolism
increase NADH/NAD+ ratio in liver --> lactic acidosis (increase pyruvate to lactate), fasting hypoglycemia, ketoacidosis, hepatosteatosis, inhibit TCA cycle.
117
What does the Mitochondria Metabolize?
Fatty acid oxidation, acetyl CoA production, TCA cycle, oxidative phosphorylation, ketogenesis
118
What does the Cytoplasm Metabolize?
glycolysis, HMP shut, synthesis of cholesterol, proteins, fatty acids and nucleotides
119
What does the Mitochondria and Cytoplasm Metabolize?
Heme synthesis, Urea cycle, gluconeogenesis
120
Phosphofructokinase 1
Glycolysis (require ATP)
Fructose 6 phosphate --> fructose 1,6 bisphosphate
(+) AMP, fructose 2,6 bisphosphate
(-) ATP, citrate
121
Fructose 1,6 bisphosphatase
Gluconeogenesis
| (-) AMP, fructose 2,6 bisphosphate
122
Isocitrate dehydrogenase
TCA Cycle
(+) ADP
(-) ATP, NADH
123
Glycogen synthase
Glycogenesis
(+) G6P , insulin, cortisol
(-) epinephrine, glucagon
124
Glycogen phosphorylase
glycogenolysis
(+) epinephrine, glucagon, AMP
(-) G6P, insulin, ATP
125
G6PD
HMP shunt
(+) NADP+
(-) NADPH
126
Carbamoyl phosphate synthetase II
De novo pyrimidine synthesis
(+) ATP, PRPP
(-) UTP
127
Glutamine PRPP amidotransferase
De novo purine synthesis
| (-) AMP, IMP, GMP
128
Carbamoyl phosphate synthetase I
Urea cycle
| (+) N acetylglutamate
129
Acetyl CoA carboxylase
Fatty acid synthesis
(+) insulin, citrate
(-) glucagon, palmitoyl CoA
130
Carnitine acyltransferase I
Fatty acid oxidation
| (-) Malonyl CoA
131
HMG CoA synthase
Ketogenesis
132
HMG CoA reductase
Cholesterol synthesis
(+) insulin, thyroxine, estrogen
(-) glucagon, cholesterol
133
Hexokinase
(glucose --> Glucose 6 phosphate) Require ATP
most tissues except liver and pancreatic B cells, high affinity, low capacity, not induced by insulin, inhibited by glucose 6 phosphate
134
Glucokinase
(glucose --> Glucose 6 phosphate) Require ATP
| liver and beta cells of pancreas, low affinity, high capacity, induced by insulin, inhibited by fructose 6 phosphate
135
Fasting state
increase glucagon --> increase cAMP --> increase PKA --> increase FBPase2 and decrease PFK2
136
Fed State
Increase insulin --> decrease cAMP --> decrease PKA --> decrease FBPase2 and increase PFK2
137
Pyruvate Dehydrogenase Complex
Active in fed state
Pyruvate --> acetyl CoA
Enzymes: thiamine pyrophosphate, lipoic acid (inhibited by arsenic), CoA, FAD, NAD+
Activated by increased NAD+/NADH ratio, increase ADP and increase Ca2+
138
Pyruvate Dehydrogenase Complex Deficiency
X linked
buildup of pyruvate that gets shunted to lactate and alanine
Neuro deficits, lactic acidosis, increase serum alanine
T(x): increase intake of ketogenic nutrients
139
Pyruvate Metabolism
1. Alanine aminotransferase (liver to muscle)
2. Pyruvate carboxylase (oxaloacetate)
3. Pyruvate dehydrogenase (TCA cycle)
4. Lactic acid dehydrogenase (RBC)
140
Electron Transport inhibitors
directly inhibit ETC --> decrease proton gradient and block ATP synthesis
Rotenone: complex 1 inhibitor
Antimycin A: complex 3 inhibitor
Cyanide, CO, azide: inhibit complex 4
141
ATP synthase inhibitors
Directly inhibit mitochondrial ATP synthase --> increase proton gradient. No ATP is produced
Oligomycin
142
Uncoupling agent
increase permeability of membrane --> decrease proton gradient and increase O2 consumption. ATP synthesis stops but ETC continues. Produces heat.
2,4 Dinitrophenol, aspirin, brown fate
143
Gluconeogenesis Irreversible enymes
Pyruvate carboxylase
PEP carboxykinase
Fructose 1,6 bisphosphatase
Glucose 6 Phosphatase
144
Pentose Phosphate Pathway
provides NADPH and ribose from glucose 6 phosphate.
| NADPH used for glutathione reduction in RBC, fatty acid and cholesterol biosynthesis.
145
Oxidative phase of PPP
Irreversible
| glucose 6 phosphate to 6 phosphogluconate (Glucose 6 phosphate dehydrogenase)
146
Nonoxidative phase of PPP
Reversible
147
Glucose 6 Phosphate Dehydrogenase defiency
X linked. African Americans. Increased malarial resistance
decrease NADPH in RBCS --> hemolytic anemia, infection
Heinz bodies- denatured globin chains precipitate within RBCs due to oxidative stress
Bite cells
148
Essential fructosuria
defect in fructokinase AR
benign asymptomatic. Hexokinase becomes primary.
Fructose in blood and urine
149
Hereditary fructose intolerance
Deficiency in aldolase B AR. Accumulation of fructose 1 phosphate --> decrease available phosphate --> inhibit glycogenolysis and gluconeogenesis.
Symptoms present after consuming fruit juice or honey.
Urine dipstick will be (-)
Hypoglycemia, jaundice, cirrhosis, vomiting
T(x): decrease intake of fructose, sucrose and sorbitol
150
Galactokinase deficiency
Deficiency in Galactokinase AR
Galactitiol accumulates if galactose is present in diet
Galactosemia and galactosuria, infantile cataracts.
151
Classic Galactosemia
Absence of galactose 1 phosphate uridyltransferase AR
Accumulation of toxic substances.
Symptoms develop when infant begins feeding
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
T(x): no galactose or lactose
152
Sorbitol
trap glucose by converting to sorbitol via aldose reductase. intracellular sorbitol accumulation --> osmotic damage.
153
Lactase Deficiency
Intestinal brush border
Primary: age dependent decline after childhood. (asian, AA, NA)
Secondary: loss of intestinal brush border due to gastroenteritis (rotavirus)
Congenital
Stool- acidic and breath increases H+
Bloating cramps, flatulence, osmotic diarrhea
154
Hyperammonemia
Flapping tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurred vision.
increase NH3 changes a ketoglutarate, glutamate, GABA and glutamine
T(x) limit protein in diet
155
Ornitine Transcarbamylase Deficiency
X linked Urea Cycle Disorder
Body cannot eliminate ammonia (first few days of life)
increase orotic acid in blood and urine, decrease BUN, symptoms of hyperammonemia
156
PKU
Low phenylalanine hydroxylase or BH4 cofactor (AR)
increase pheyl ketones in urine
Intellectual disability, growth retardation, seizures, fair complexion, eczema, musty body order
t(x): decrease phenylalanine and increase tyrosine in diet., BH4 supplement.
157
Maple Syrup Urine Disease
blocked degradation of branched amino acids (AR)(isoleucine, leucine, valine) due to decreased branched chain a ketoacid dehydrogenase--> increase a ketoacids in blood
vomit, poor feeding, urine smells like maple syrup, severe CNS defects, intellectual disability, death
T(x): restrict isoleucine, leucine, valine in diet and thiamine supplement
158
Alkaptonuria
AR
congenital deficiency of homogentisate oxidase (tyrosine--> fumarate) --> buildup of homogentisic acid in tissues
benign
bluish black connective tissue, ear cartilage and slera
urine turns black on prolonged exposure to air
debilitating arthralgia
159
Homocystinuria
AR
excess homocysteine in urine
osteoporosis, Marfanoid habitus, ocular changes, cardiovascular effects, kyphosis, intellectual disability, fair complexion, Lens down and in
160
Cystinuria
AR
Renal PCT and intestinal amino acid transporter defect
--> prevents reabsorption of Cystine, ornithine, lysie, arginine. Excess cystine in urine --> hexagonal dtones
T(x): urinary alkalinization and chelating agents
D(x): urinary CN-nitroprusside test
161
Organic acidemias
present in infancy with poor feeding, vomiting, hypotonia, high anion gap, metabolic acidosis, hepatomegaly, seizures, organic acid accumulation
inhibit gluconeogenesis and hyperammonemia
162
Propionic acidemia
Deficient in propionyl CoA carboxylase --> increase propionyl CoA and decrease methylmalonic acid
T(x) low protein diet limited in Valiine, odd chain FA, methionine, isoleucine, threonine
163
Methylmalonic acidemia
deficiency in methylmalonyl CoA mutase or vitamin B12
| T(x) low protein diet limited in Valiine, odd chain FA, methionine, isoleucine, threonine
164
Glycogen in skeletal muscle
glycogenolysis --> G1P --> G6P -->exercise
165
Glycogen in Hepatocytes
stored and undergoes glycogenolysis to maintain blood sugar
166
Von Gierke
Deficient glucose 6 phosphatase
Sever fasting hypoglycemia, increase glycogen in liver and kidneys, increase blood lactate, Triglycerides and uric acid, hepatomegaly
T(x) oral glucose, avoid fructose and galactose
167
Pompe
Deficient Lysosomal acid a 1,4 glucosidase
| Cardiomegaly, hypertrophic cardiomyopathy, hypotonia, exercise intolerance
168
Cori Disease
Deficient debranching enzymes
| normal blood lactate, cardiomyopathy, fasting hypoglycemia.
169
McArdle Disease
Deficient Skeletal Muscle glycogen phosphorylase.
increase glycogen in muscle but muscle cannot break it down --> muscle cramps, myoglobinuria with strenuous exercise, arrhythmia
170
Tay Sachs
Deficient Hexaminidase A --> accumulated GM2 ganglioside AR
| progressice neurodegeneration, developmental delay, hyperreflexia, cherry red spot, lysosomes with onion skin
171
Fabry Disease
Deficient a galactosidase A --> accumulate ceramide trihexoside XR
early: peripheral neuropathy, angiokeratomas, hypohidrosis
Late: renal failure, cardio disease
172
Metachromatic leukodystrophy
Deficient Arylsulfatase A --> Cerebroside sulfate AR
| Central and peripheral demyelination with ataxia and dementia
173
Krabbe Disease
Deficient Galactocerebrosidase --> accumulate glacatocerebroside AR
peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells
174
Gaucher Disease
Deficient Glucocerebrosidase --> accumulate glucocerebroside AR
Hepatomegaly, pancytopenia, osteoporosis, avascular necrosis of femur, bone crises, gaucher cells
175
Niemann Pick
Deficient sphingomyelinase --> accumulate sphingomyelin AR
| progressive neurodegeneration, hepatosplenomegaly, foam cells, cherry spot
176
Hurler Syndrome
Deficient iduronidase --> accumulate heparan sulfate AR
| Development delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
177
Hunter Syndrome
deficient iduronate 2 sulfatase --> accumulate heparan sulfate XR
mild Hurler + aggressive behavior, no corneal clouding
178
Systemic Primary Carnitine Deficiency
no cellular uptake of carnitine --> no transport of LCFAs into mitochondria --> toxic accumulation of LCFAs in cytosol
weakness, hypotonia, hypoketotic hypoglycemia, dilated cardiomyopathy
179
Medium chain acyl CoA dehydrogenase deficiency
decreased ability to break down fatty acids into acetyl CoA --> accumulate fatty acyl carnitines in blood with hypoketotic hypoglycemia
vomiting, lethargy, seizure, coma, liver dysfunction, hyperammonemia, death
180
Ketone excess caused by...
prolonged starvation, DKA, alcoholism (excess NADH)
breath smells like acetone
Urine test for ketones can detect acetoacetate not B hydroxybutyrate
181
Choeslteryl ester transfer protein
mediates transfer of cholesteryl esters to other lipoprotein particles
182
Hepatic lipase
degrade TG --> IDL
183
Hormone sensitive lipase
Degrade TG in adipocytes
184
Lecithin cholesterol acyltransferase
catalyze esterification of 2/3 plasma cholesterol
185
Lipoprotein lipase
degrade TG in chylomicrons
186
Pancreatic lipase
degrade dietary TG in small intestine
187
PCSK9
degrade LDL recpetor --> increase serum LDL
| inhibition --> increase LDL receptor recycing --> decrease serum LDL
188
Apolipoprotein E
Everything except LDL
189
Apolipoprotein A
Only HDL
190
Apolipoprotein C
chylomicron, VLDL, IDL, HDL
191
Apolipoprotein B48
Chylomicron
192
Apolipoprotein B100
VLDL, IDL, HDL
193
Abetalipoproteinemia
AR, mutation in MTP
Chylomicrons, VLDL, LDL absent, and deficiency in B48, B100.
infant severe fat malabsorption, steatorrhea, failure to thrive. Later retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, ataxia, acanthocytosis.
194
Hypochylomicronemia
AR Lipoprotien lipase or apolipoprotein C deficiency
increase blood level chylomicron, TG and cholesterol
Pancreatitis, hepatosplenomegaly and pruritic xanthomas
195
Familial hypercholesterolemia
AD absent or defective LDL receptor or defective B100
increase LDL and cholesterol
accelerated atherosclerodid, tendon xanthomas and corneal arcus
196
Dysbetalipoproteinemia
AR defective ApoE.
increase blood chylomicrons, VLDL
premature atherosclerosis, tuberoeruptive and pamar xanthomas
197
Hypertriglyceridemia
AD Hepatic overproduction of VLDL
increase blood VLDL and TG
pancreatitis, insulin resistance
