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Biochemistry Flashcards

1
Q

DNA methylation at CpG islands - Methyltransferase using SAM.

in euk, cytosine-guanine dinucleotide repeats in the promoter region of genes are preferentially methylated as part of the epigenetic code

A

Represses transcription of those genes

Note - Mechanism of imprinting.

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2
Q

Histone methylation.

Note - H1 is linker histone

A

Usually reversibly represses DNA transcription

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3
Q

Histone acetylation.

A

Relaxes coiling and allows for transcription

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4
Q

Amino acids necessary for de novo purine synthesis - Conversion of PRPP to IMP

A

Glycine
Aspartate
Glutamine

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5
Q

Required for Pyrimidine base production.

A

Aspartate

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6
Q

Reduced degradation of Adenosine and Deoxyadenosine to Inosine/Hypoxanthine - Increased dATP and toxicity in lymphocytes.

A

ADENOSINE DEAMINASE (ADA) DEFICIENCY

One of the major causes of autosomal recessive SCID.

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7
Q

Defective purine salvage due to absent HGPRT - Converts Hypoxanthine to IMP / Guanine to GMP.

Results in increased Uric Acid/Purine synthesis

A

LESCH-NYHAN SYNDROME

X-linked recessive.

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8
Q

Symptoms of Lesch-Nyhan syndrome.

A 
Hyperuricemia (orange "sand" sodium urate crystals in diaper)
Gout
Pissed off (aggression, self-mutilation)
Retardation
dysTonia

Treat with Allopurinol or Febuxostat

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9
Q

5’ - 3’ / 3’ - 5’ exonuclease activity for removal of RNA primers and damaged DNA

A

DNA POL I

Prokaryotes only

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10
Q

5’ - 3’ synthesis with 3’ - 5’ exonuclease activity for proofreading

A

DNA POL III

Prokaryotes only

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11
Q

RNA-dependent DNA-pol (reverse transcriptase) adds DNA (TTAGGG) to 3’ end of lagging template strand - end replication problem

A

TELOMERASE

Eukaryotes only - dysregulated in cancer cells allowing for unlimited replication.

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12
Q

Substitution of glutamic acid with valine (missense mutation).

A

Sickle Cell Disease

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13
Q

Nucleotide substitution resulting in early stop codon and usually a nonfunctional protein.

A

Nonsense mutation

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14
Q

Deletion or insertion of a number of nucleotides not divisible by 3 resulting in misreading of all nucleotides downstream (frameshift).

A

Duchenne Muscular Dystrophy

Tay-Sachs Disease

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15
Q

LAC operon activation in presence of low glucose and high lactose.

A

Increased adenylate cyclase activity
Increased generation of cAMP from ATP
Activation of catabolite activator protein (CAP)

Unbinding of repressor protein from repressor/operator site

Both result in increased transcription

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16
Q

Defective nucleotide excision repair (G1) preventing repair of pyrimidine dimers secondary to UV exposure.

A

Xeroderma Pigmentosum

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17
Q

Removal of altered base and creation of AP site with glycosylate for AP-endonuclease (throughout cell cycle).

A

Base excision repair (spontaneous/toxic deamination)

Note - Endonuclease cleaves 5’ end and lyase cleaves 3’ sugar-phosphate

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18
Q

Defective mismatch repair (G2).

A

Lynch Syndrome (HNPCC)

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19
Q

Defective nonhomologous end joining for double-stranded breaks.

A

Ataxia Telangiectasia

Fanconi Anemia

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20
Q

Modified 3’ OH preventing addition of next nucleotide containing 5’ triphosphate.

A

CHAIN TERMINATION

DNA replication blocking drugs

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21
Q

Inhibits RNA polymerase II causing hepatotoxicity.

A

Alpha-amanitin (Amanita Phalloides)

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22
Q

Inhibition both prokaryotic and eukaryotic RNA pol.

A

Actinomycin D

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23
Q

Antibodies to spliceosomal snRNPs (Lariat loop).

A

ANTI-SMITH

Specific for SLE.

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24
Q

Antibodies to U1 RNP.

A

Mixed connective tissue disease

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25
Contains sequence necessary for tRNA-ribosome binding.
T-arm Molecule is a loop with 5' end base paired to 3' end - 3' end contains CCA acceptor stem
26
Necessary for tRNA recognition by correct aminoacyl-tRNA synthetase (ATP-dependent).
D-arm Malfunction in results in mischarged tRNA (right codon, wrong amino acid).
27
Steps of eukaryotic protein synthesis (GTP-dependent).
Initiation: tRNA-Met binds to P site of 40s to recruit 60s (80s total). Elongation: tRNA binds A site, rRNA transfers polypeptide to amino acid on A site, ribosome advances 5' to 3' moving new tRNA to P site and old tRNA to E site. Termination: Stop codon recognized by releasing factor adding water instead of AA to growing polypeptide.
28
Inhibition of G1-S progression.
p53 induces p21 Inhibition of CDK Hypophosphorylated Rb inactivates E2F (transcription factor) Mutation results in Li-Fraumeni Syndrome.
29
Permanent cell types (remain in G0) - regenerate from stem cells only.
Neurons Skeletal and Cardiac muscle RBCs
30
Stable (quiescent) cell types - must be stimulated to enter G1.
Hepatocytes | Lymphocytes
31
Rich in RER.
Mucus-secreting goblet cells | Plasma cells
32
Rich in SER (steroid synthesis, detoxification).
Hepatocytes | Steroid producing cells (adrenal cortex, gonads)
33
Coarse facial features Clouded corneas Restricted joint movement High plasma levels of lysosomal enzymes
I-CELL DISEASE Defect in N-acetylglucosaminyl-1-phosphotransferase Failure of golgi to phosphorylate mannose residues Proteins secreted extracellularly instead of to lysosomes
34
Absent or dysfunctional SRP.
Protein accumulation in the cytosol (traffic protein from ribosome to RER).
35
Traffic proteins from cis-Golgi back towards ER.
COPI COPII transports from ER to cis-Golgi.
36
Traffic proteins from trans-Golgi to lysosomes, or plasma membrane to endosomes.
Clathrin
37
Vimentin stain.
MESENCHYME - FIBROBLASTS, ENDOTHELIAL, MACROPHAGES Sarcoma Endometrial carcinoma Renal cell carcinoma Meningioma
38
Desmin stain.
MUSCLE Rhabdomyosarcoma
39
Cytokeratin stain.
EPITHELIUM Epithelial tumors (e.g. SCC)
40
GFAP (glial fibrillary acid protein) stain.
NEUROGLIA (ASTROCYTES, SCHWANN, OLIGODENDROGLIA) Astrocytoma Glioblastoma
41
Neurofilament stain.
NEURONS Neuronal tumors (neuroblastoma)
42
Drugs that act on microtubules.
(Microtubules Get Constructed Very Poorly) ``` Mebendazole Griseofulvin Colchicine Vincristine Paclitaxel ```
43
``` Infertility (M/F) Ectopic pregnancy Bronchiectasis Recurrent sinusitis Situs inversus (dextrocardia) ```
KARTAGENER SYNDROME (PRIMARY CILIARY DYSKINESIA) Autosomal recessive Dynein mutation leading to immotile cilia
44
Type I collagen (90%).
``` Bone Skin Tendon Fascia Cornea Late wound repair (> 3 wks) ```
45
Type II collagen.
Cartilage Vitreous body Nucleus pulposus
46
Type III collagen.
Reticulin (viscera, marrow) Blood vessels/lymphatics Granulation tissue (< 3 wks)
47
Type IV collagen.
Basement membrane Basal lamina Lens
48
Collagen synthesis.
Synthesis of preprocollagen - Mostly Glycine Hydroxylation of Proline/Lysine (requires Vit C) Glycosylation / triple helix formation via disulfide bonds From ER to Golgi Exocytosis of procollagen Cleavage of procollagen C/N terminals forming insoluble tropocollagen Covalent cross-linking of staggered tropocollagen via lysyl oxidase (acts on lysine) Formation of fibrils
49
Multiple fractures with minimal trauma Blue sclera Hearing loss Tooth abnormalities (dentin)
OSTEOGENESIS IMPERFECTA Autosomal dominant (COL1A1/2) Defect in triple helix formation of Type I collagen.
50
``` Hypermobile joints Joint dislocation Hyperextensible skin Easy bruising and bleeding (Berry and Aortic aneurysms) ```
EHLERS-DANLOS SYNDROME Type V collagen defect - Procollagen Peptidase or Lysyl Hydroxylase Note - Forms soluble collagen that cannot cross-link
51
Brittle, lanky hair Growth retardation Hypotonia
MENKES DISEASE X-linked recessive (ATP7A). Defect in copper absorption - Decreased activity of Lysyl Oxidase and thus covalent cross-linking.
52
``` Tall with long extremities Arachnodactyly Hypermobile joints Cystic medial necrosis of aorta (aortic dissection) Mitral valve prolapse Subluxation of lenses (upwards) ```
MARFAN SYNDROME ``` Autosomal dominant Fibrillin FBN1 (glycoprotein sheath around elastin) on Chromosome 15 ```
53
Elastin synthesis.
Tropoelastin Proline/Lysine remain non-hydroxylated Excretion into ECM and interaction with fibrillin scaffold Lysyl oxidase (requires Cu) forms Desmosine cross-links on Lysine - gives elastic properties
54
Blotting procedures.
``` Northern = RNA Southern = DNA Western = Protein (confirmatory for HIV after ELISA) ```
55
Used to compare gene expression levels of thousands of genes between two samples.
Microarray
56
Used to assess size and protein expression of individual cells in a sample.
Flow cytometry
57
Used to detect the presence of a specific antigen or antibody in a blood sample.
ELISA Note - Unlike Western blot the serum is tested directly
58
Inheritance of mutation in tumor suppressor gene requires complementary allele to be mutated before cancer develops.
LOSS OF HETEROZYGOSITY E.g. Retinoblastoma, HNPCC, Li-Fraumeni
59
Heterozygote producing a nonfunctional protein that also prevents function of normal protein.
Dominant negative mutation
60
Cafe-au-lait spots Polyostotic fibrous dysplasia Precocious puberty
MCCUNE-ALBRIGHT SYNDROME Mutation in G-protein signaling - only survivable if somatic mosaicism.
61
Mutations at different loci produce the same phenotype.
LOCUS HETEROGENEITY E.g. Albinism
62
Different mutations in the same locus produce the same phenotype.
ALLELIC HETEROGENEITY E.g. B-Thalassemia
63
Individual manifesting a recessive disorder when only one parent is a carrier.
UNIPARENTAL DISOMY Euploid.
64
Hardy-Weinberg equilibrium
p2+2pq+q2 X-linked recessive in males = p X-linked recessive in females = p2
65
``` Intellectual disability Hyperphagia Obesity Hypogonadism Hypotonia ```
PRADER-WILLI SYNDROME most commonly due to microdeletions involving the PATERNAL chromosome 15q11-13 region or maternal uniparental disomy OR Maternal imprinting on chromosome 15 - Father mutated
66
Intellectual disability Inappropriate laughter Seizures Ataxia
ANGELMAN SYNDROME Parental imprinting on chromosome 15 - Maternal gene mutated Loss of maternally inherited allele from chromosome 15. Due to MATERNAL microdeletion or paternal uniparental disomy. Note - Occasionally paternal uniparental disomy
67
Bone pain and skeletal abnormalities due to increased phosphate wasting at proximal tubules.
HYPOPHOSPHATEMIC (VIT D RESISTANT) RICKETS X-linked dominant
68
``` Autism Large ears Long face with large jaw Macroorchidism Hypotonia Hyperextensible fingers Mitral valve prolapse ```
FRAGILE X SYNDROME X-linked dominant CGG repeat in FMR1 gene resulting in methylation
69
Constitutive action of fibroblast growth factor receptor 3 (FGFR3) inhibits chondrocyte proliferation and thus endochondral ossification.
ACHONDROPLASIA ``` Autosomal dominant Full penetrance Chromosome 4 ("4 short limbs") ```
70
Bilateral massive enlargement of kidneys due to mutation in PKD1 on chromosome 16.
ADPKD ``` Autosomal dominant Chromosome 16 ("16 letters in polycystic kidney") ```
71
Numerous adenomatous polyps following puberty.
FAMILIAL ADENOMATOUS POLYPOSIS Autosomal dominant APC gene on Chromosome 5q ("5 letters in polyp")
72
``` Telangiectasias Recurrent epistaxis AVM GI bleeding Hematuria ```
HEREDITARY HEMORRHAGIC TELANGIECTASIA (OSLER-WEBER-RENDU) Autosomal dominant
73
Spheroid erythrocytes due to spectrin or ankyrin defect. Elevated MCHC Elevated RDW
HEREDITARY SPHEROCYTOSIS Autosomal dominant
74
Depression Progressive dementia Choreiform movements Caudate atrophy Elevated dopamine Decreased GABA Decreased Ach
HUNTINGTON DISEASE Autosomal dominant CAG repeat on Chromosome 4
75
Multiple malignancies at an early age | SBLA - Sarcoma, Breast, Lung, Adrenal
LI-FRAUMENI SYNDROME Autosomal dominant Mutation in TP53
76
``` Cafe-au-lait spots Cutaneous neurofibromas Optic gliomas Lisch nodules (iris) Pheochromocytoma ```
NEUROFIBROMATOSIS TYPE 1 (VON RECKLINGHAUSEN) Autosomal dominant Full penetrance with variable expression NF1 gene on Chromosome 17 ("17 letters in von recklinghausen")
77
Bilateral acoustic schwannomas Juvenile cataracts Meningiomas Ependymomas
NEUROFIBROMATOSIS TYPE 2 Autosomal dominant NF2 gene on Chromosome 22 ("type 2 = 22")
78
Cerebellar hemangioblastomas Clear cell RCC Pheochromocytoma
VON HIPPEL-LINDAU DISEASE VHL tumor suppressor gene deletion on Chromosome 3 ("3 words in von hippel-lindau")
79
Autosomal recessive disorders.
ENZYME DEFICIENCIES Except Hunter's, Fabry, OTC (X-linked recessive).
80
Recurrent pulmonary infections (s. aureus, pseudomonas) Nasal polyps Chronic bronchitis and bronchiectasis (reticulonodular) Pancreatic insufficiency/exocrine atrophy Meconium ileus Biliary cirrhosis Infertility in men (absent vas deferens) Subfertility in women (thick cervical mucous) Nail clubbing
CYSTIC FIBROSIS Autosomal recessive CFTR gene on chromosome 7 - ATP-gated Cl channel
81
Management of cystic fibrosis.
Confirm with... Sweat Cl > 60 Negative transepithelial potential difference Elevated immunoreactive trypsinogen (newborn screen) ``` Lumacaftor/Ivacaftor to increase membrane channels Chest physiotherapy Albuterol Dornase alfa (DNAse) Hypertonic saline Azithromycin (anti-inflammatory) Pancreatic enzymes ```
82
Pathophysiology of dF508 cystic fibrosis.
ATP-gated Cl channel misfolded and degraded Cl channels reaching the membrane are dysfunctional Decreased Cl secretion (in to out channel) Compensatory Na/water reabsorption Abnormally thick mucus in lungs and GI tract ``` Hyponatremia (NaCl lost in sweat; out to in channel) Low ECF Na/water leads to renal K/H wasting Contraction alkalosis (like loop diuretic) ```
83
Common X-linked recessive disorders ("Be Wise Fools GOLD Heeds Hope") Note - Paternal to son transmission does not occur
``` Bruton agammaglobulinemia Wiskott-Aldrich syndrome Fabry disease G6PD deficiency OTC deficiency Lesch-Nyhan Dystrophy (muscular) Hunter syndrome Hemophilia ```
84
``` Pelvic girdle weakness Waddling gait < 5 y/o Gower's maneuver Calf pseudohypertrophy (fibrofatty replacement) Dilated cardiomyopathy (mortality) ``` Elevated CK and aldolase
DUCHENNE MUSCULAR DYSTROPHY X-linked recessive frameshift mutation resulting in truncated dystrophin (links ECM to actin) and thus myonecrosis. Confirm with biopsy/western blot.
85
Myopathy Lactic acidosis CNS disease Ragged red fibers on muscle biopsy
MITOCHONDRIAL MYOPATHIES Transmitted only through the mother with heteroplasmy (variable expression).
86
Pelvic girdle weakness with onset in adolescence.
BECKER MUSCULAR DYSTROPHY X-linked recessive non-frameshift insertion in dystrophin gene (partially functional).
87
``` Myotonia (endless grip) Muscle wasting Cataracts Testicular atrophy Frontal balding Arrhythmia ```
MYOTONIC DYSTROPHY TYPE 1 Autosomal dominant CTG repeat in myotonin protein kinase (DMPK) gene
88
Trinucleotide repeat expansion diseases. "X-Girlfriend's, First Aid, Helped Ace, My Test"
``` Fragile X (CG-) Friedreich ataxia (GA-) Huntington disease (CA-) Myotonic dystrophy (CT-) ```
89
``` Intellectual disability Flat facies Epicanthal folds Single palmar crease Duodenal atresia Hirschsprung's disease AV septal defect, ASD, VSD Early-onset Alzheimer's ALL and AML ```
DOWN'S SYNDROME (TRISOMY 21) 1st trimester: Increased nuchal translucency Increased b-hCG Decreased PAPP-A ``` 2nd trimester: Increased b-hCG Increased inhibin A Decreased a-fetoprotein Decreased estriol ```
90
``` Severe intellectual disability Rocker-bottom feet Micrognathia Low-set ears Clenched hands with overlapping fingers Congenital heart disease ```
EDWARDS SYNDROME (TRISOMY 18) 1st trimester: Decreased b-hCG Decreased PAPP-A ``` 2nd trimester: Decreased b-hCG Decreased or normal inhibin A Decreased a-fetoprotein Decreased estriol ```
91
``` Severe intellectual disability Rocker-bottom feet Microcephaly Cleft lip and palate Holoprosencephaly Polydactyly Congenital heart disease Omphaloceles ```
PATAU SYNDROME (TRISOMY 13) 1st trimester: Decreased b-hCG Decreased PAPP-A
92
``` Intellectual disability Microcephaly High pitched crying Epicanthal folds Cardiac abnormalities (VSD) ```
CRI-DU-CHAT SYNDROME Congenital microdeletion of short arm of Chromosome 5
93
``` Intellectual disability Elfin facies Extreme friendliness Well-developed verbal skills Hypercalcemia Cardiovascular problems (supravalvular aortic stenosis) ```
WILLIAMS SYNDROME Congenital microdeletion of long arm of Chromosome 7
94
``` Cleft palate Abnormal facies Thymic aplasia Cardiac defects (truncus, TOF) Hypocalcemia ```
22q11 DELETION SYNDROMES Failed neural crest migration - Aberrant development of 3rd/4th branchial pouches DiGeorge syndrome - Thymic, Parathyroid, and Cardiac Velocardiofacial syndrome - Palate, Facial, and Cardiac Note - Detected with FISH
95
Fat soluble vitamins.
A, D, E, K Absorption dependent on gut and pancreas.
96
``` Vitamin deficiency resulting in... Night blindness Infections Squamous metaplasia to keratinizing epithelium Corneal degeneration Conjunctival spots ```
VITAMIN A (RETINOL) DEFICIENCY
97
Vitamin toxicity resulting in... Acutely - N/V, Vertigo, Blurred vision Chronically - Alopecia, Dry Skin, Transaminitis, Pseudotumor Cerebri, Arthralgia Note - Also Teratogenic
VITAMIN A (RETINOL) TOXICITY
98
Vitamin deficiency resulting in... Polyneuritis with muscle wasting - Dry beriberi Dilated cardiomyopathy and HFpEF - Wet beriberi
VITAMIN B1 (THIAMINE) DEFICIENCY a-Ketoglutarate/Pyruvate Dehydrogenase dysfunction - Impaired glucose breakdown leads to ATP depletion worsened by glucose infusion Diagnosed by increased RBC Transketolase activity following B1 administration - Transketolase used in non-oxidative step of HMP shunt
99
Vitamin deficiency resulting in... ``` Cheilosis Stomatitis Glossitis Seborrheic dermatitis Corneal calcification ```
VITAMIN B2 (RIBOFLAVIN) DEFICIENCY Generates FAD/FMN Needed for... ETC Succinate Dehydrogenase (TCA)
100
Vitamin deficiency resulting in... Diarrhea Dementia Dermatitis (collar rash, hyperpigmented limbs)
VITAMIN B3 (NIACIN) DEFICIENCY Generates NAD Needed for... Isocitrate dehydrogenase a-ketoglutarate dehydrogenase Malate dehydrogenase
101
Causes of B3 deficiency
Hartnup disease Malignant Carcinoid - Increased tryptophan catabolism Isoniazid
102
Mechanism of Hartnup disease
Autosomal recessive deficiency of neutral amino acid transporters in kidneys and gut Neutral aminoaciduria and decreased absorption Decreased tryptophan for conversion to Niacin Treat with high protein diet and Nicotinic Acid
103
Facial flushing caused by prostaglandins Hyperglycemia Hyperuricemia Used to lower VLDL and raise HDL
VITAMIN B3 TOXICITY Note - Can treat flushing with ASA
104
Vitamin deficiency resulting in... Dermatitis Enteritis Alopecia Adrenal insufficiency
VITAMIN B5 (PANTOTHENIC ACID) DEFICIENCY Generates CoA
105
Vitamin deficiency resulting in... ``` Cheilosis, stomatitis, glossitis CNS abnormalities (neurotransmitter deficiency) Peripheral neuropathy (with Isoniazid, OCP) Sideroblastic anemia (impaired hemoglobin synthesis) ```
VITAMIN B6 (PYRIDOXINE) DEFICIENCY Generates PLP Needed for... Transamination
106
Vitamin deficiency resulting in... Dermatitis Enteritis Alopecia Metabolic acidosis Note - In the setting of excess ingestion of raw egg whites
VITAMIN B7 (BIOTIN) DEFICIENCY Needed for... Carboxylation reactions
107
Vitamin deficiency resulting in... ``` Macrocytic megaloblastic anemia Hypersegmented PMN Glossitis Increased homocysteine Normal methylmalonic acid ``` Note - In the setting of alcoholism and pregnancy
VITAMIN B9 (FOLATE) DEFICIENCY Generates THF Needed for... DNA/RNA base synthesis Note - Absorbed in jejunum
108
Vitamin deficiency resulting in... ``` Macrocytic megaloblastic anemia Hypersegmented PMN Paresthesias Subacute combined degeneration Increased homocysteine Increased methylmalonic acid (neurotoxic) ``` Note - Deficiency takes years
VITAMIN B12 (COBALAMIN) DEFICIENCY Needed for... DNA synthesis Note - Absorbed in ileum
109
Causes of Vitamin B12 (Cobalamin) deficiency
``` Malabsorption Pernicious anemia (IF antibodies) Gastric bypass (lack of IF) Resection of terminal ileum Veganism ```
110
Vitamin deficiency resulting in... ``` Swollen gums Bruising/Petechiae Poor wound healing Corkscrew hair Myalgia Hemarthrosis Anemia Immunosuppression ```
VITAMIN C (ASCORBIC ACID) DEFICIENCY (SCURVY) Antioxidant activity reduces iron to Fe2+ for absorption
111
Vitamin C (Ascorbic acid) toxicity. Cholecalciferol in milk/skin Calcifediol (25-OH) in storage Calcitriol (1,25-OH) in active form
``` Nausea/Vomiting Diarrhea Fatigue Calcium oxalate nephrolithiasis Iron toxicity in hemochromatosis ```
112
Vitamin deficiency resulting in... Bone pain Deformity in children Osteomalacia/muscle weakness in adults Hypocalcemic tetany
VITAMIN D DEFICIENCY
113
Vitamin D toxicity
Hypercalcemia Hypercalciuria Loss of appetite Stupor
114
Vitamin deficiency resulting in... Hemolytic anemia (oxidative damage) Neuromuscular disease (Vit B12-like damage) Acanthocytes (spur cells) Infertility
VITAMIN E DEFICIENCY
115
Vitamin deficiency resulting in... Neonatal hemorrhage Increased PT/PTT Normal bleeding time Note - Synthesized by intestinal flora
VITAMIN K DEFICIENCY
116
Vitamin K dependent clotting factors (inhibited by Warfarin)
II, VII, IX, X, and C/S
117
Deficiency resulting in... ``` Delayed wound healing Hypogonadism Decreased adult hair Dysgeusia (metallic taste) Anosmia Acrodermatitis enteropathica (dermatitis/alopecia around orifices) ```
ZINC DEFICIENCY
118
Protein malnutrition resulting in a small child with a swollen abdomen... Malnutrition Edema (decreased plasma oncotic pressure) Anemia Liver (fatty changes, decreased Apo synthesis)
KWASHIORKOR
119
Total calorie malnutrition resulting in emaciation (tissue and muscle wasting, loss of subQ fat).
MARASMUS
120
Antidote for methanol or ethylene glycol poisoning.
FOMEPIZOLE Inhibits alcohol dehydrogenase preventing buildup of acetaldehyde.
121
Treatment for alcoholism by worsening hangover symptoms.
DISULFIRAM Inhibits acetaldehyde dehydrogenase allowing for accumulation of acetaldehyde.
122
Metabolic effects of increased NADH/NAD ratio (chronic alcoholism).
Lactic acidosis (Pyruvate to Lactate) Fasting hypoglycemia (Less Oxaloacetate prevents gluconeogenesis) Hepatosteatosis (shunting of DHAP to Glycerol/TG production) Ketoacidosis (inhibition of TCA shunting Acetyl-CoA to Ketogenesis)
123
Pentose phosphate pathway (HMP shunt) products (2) and their use
NADPH (oxidative, irreversible): Steroids, Cholesterol, FFA synthesis Ribose-5-Phosphate (nonoxidative, reversible): Nucleotide synthesis Note - NADPH also required for oxidative burst
124
First committed step of glycolysis.
GLUCOSE + ATP = GLUCOSE-6-P Low concentrations: Via Hexokinase in tissues (high affinity, low capacity) - Feedback inhibited by Glucose-6-Phosphate. High concentrations/Presence of insulin: Via Glucokinase in liver/pancreas (low affinity, high capacity) - Feedback inhibited by Fructose-6-Phosphate. Note - Mutation in Glucokinase responsible for MODY (responsible for glucose sensing in beta cells)
125
Rate limiting step of glycolysis.
FRUCTOSE-6-P + ATP = FRUCTOSE-1,6-BP By Phosphofructokinase-1 Feedback inhibited by ATP and Citrate Feedback activated by AMP and F-2,6-BP
126
Reversible production of ATP. Note - Erythrocytes bypass this step in order to produce 2,3-BPG (no ATP)
1,3-BPG = 3-PG + ATP By Phosphoglycerate kinase Note - Production of 1,3-BPG requires NAD
127
Irreversible production of ATP.
Phosphoenolpyruvate = Pyruvate + ATP By Pyruvate kinase Feedback inhibited by ATP and Alanine Feedback activated by Fructose-1,6-BP
128
Regulation by Fructose-2,6-BP Activates PFK-1 Inhibits F-1,6-Bisphosphatase
``` Fasting: Increased Glucagon Increased cAMP/Activated PKA Increased Fructose-2,6-Bisphosphatase Decreased Fructose-2,6-BP Gluconeogenesis ``` ``` Fed: Increased Insulin Decreased cAMP/deactivated PKA Increased PFK-2 activity Increased Fructose-2,6-BP Glycolysis ```
129
Pyruvate dehydrogenase complex. | "TLC For Nancy"
PYRUVATE + NAD + COA = ACETYL-COA + CO2 + NADH ``` Requires: Thiamine (B1) Lipoic acid CoA (B5) FAD (B2) NAD (B3) ``` Feedback inhibited by NADH, ATP, Acetyl-CoA Feedback activated by NAD, ADP, Ca
130
Vomiting Rice water stools Garlic breath
ARSENIC POISONING Inhibits lipoic acid of pyruvate dehydrogenase complex.
131
Pyruvate metabolism
Alanine transfers amino groups to liver (ALT) Oxaloacetate (PC) Acetyl-CoA for TCA (PDH) Lactate (LDH) in RBC, WBC
132
Order of TCA cycle. | "Citrate Is Krebs Starting Substrate For Making Oxaloacetate"
``` Citrate Isocitrate a-Ketoglutarate Succinyl-CoA Succinate (requires GDP) Fumarate (requires FAD) Malate Oxaloacetate ``` Citrate synthase combines Oxaloacetate and Acetyl-CoA to replenish Citrate
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First irreversible/rate limiting step of TCA.
ISOCITRATE + NAD = A-KETOGLUTARATE + NADH By Isocitrate dehydrogenase
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Second irreversible step of TCA.
A-KETOGLUTARATE + NAD = SUCCINYL-COA + NADH By a-KG dehydrogenase complex (same as PDH)
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Neurologic deficits Lactic acidosis Increased serum Alanine in infancy
PYRUVATE DEHYDROGENASE DEFICIENCY Pyruvate shunted to Lactate and Alanine Increased intake of exclusively ketogenic amino acids (Lysine, Leucine)
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Electron transport chain mechanism.
NADH (complex I) and FADH2 (complex II; succinate dehydrogenase) donate electrons to establish H gradient for ATP synthase (Complex V). 1 NADH = 2.5 ATP, 1 FADH2 = 1.5 ATP Note - Lactate dehydrogenase responsible for NAD regeneration in anaerobic conditions
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Electron transport inhibitors.
RotenONE (complex I) Antimycin A or An3mycin A (complex III) CO/CN ("four letters," complex IV)
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Uncoupling agents - loss of proton gradient but electron transport continues thereby generating heat instead.
2,4-Dinitrophenol (weight loss supplement) Aspirin overdose Thermogenin (brown fat)
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``` Gluconeogenesis irreversible enzymes... Pyruvate to Oxaloacetate (Biotin) Oxaloacetate to Phosphoenolpyruvate (GTP) F-1,6-BP to F-6-P G-6-P to Glu ``` Note - Odd chained FAs produce Propionyl-CoA which enters TCA cycle as Succinyl-CoA to undergo gluconeogenesis Note - Only occurs in liver as skeletal muscle lacks enzyme for G-6-P to Glu
Pyruvate Carboxylase (Mito) Phosphoenolpyruvate Carboxykinase (Cytosol) Fructose-1,6,-BPase (Cytosol) Glucose-6-Pase (ER) Note - Malate shuttle transfers Oxaloacetate out of mitochondria
140
Glucose production from odd-chain fatty acids.
Propionyl-CoA enters TCA cycle as succinyl CoA and then undergo gluconeogenesis Note - Propionyl-CoA carboxylase requires Biotin
141
Oxidative (irreversible, rate-limiting) step of HMP shunt.
GLUCOSE-6-P = RIBULOSE-5-P + NADPH By Glucose-6-P dehydrogenase Feedback inhibited by NADPH
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Hemolytic anemia in the presence of fava beans, sulfonamides, primaquine, antituberculosis drugs, or infections. On smear Heinz bodies (denatured hemoglobin) and Bite cells (from removal of Heinz bodies by spleen).
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY X-linked recessive - Decreased NADPH leads to an inability to reduce glutathione (sensitive to oxidant stress) Note - Most glycolytic enzyme deficiencies cause hemolytic anemia as RBCs can only use glucose for energy
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``` Introduction of sugar with... Failure to thrive Hypoglycemia Hypophosphatemia Reducing substances in urine ```
FRUCTOSE INTOLERANCE Autosomal recessive deficiency of Aldolase B causes... Build up of Fructose-1-P Depletion of inorganic phosphate Inhibition of glycogenolysis and gluconeogenesis Remove Fructose and Sucrose (Glucose + Fructose) More mild form due to deficiency of Fructokinase (isolated reducing substances in urine) - Compensation by Hexokinase
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``` Failure to thrive Lethargy Intellectual disability Infantile cataracts Hepatic dysfunction Renal dysfunction (aminoaciduria, hyperchloremic metabolic acidosis) Reducing substances in urine E. coli sepsis in neonates ```
GALACTOSEMIA Autosomal recessive deficiency of Galactose-1-P uridyltransferase (GALT) causes build up of Galactose-1-phosphate Remove Galactose and Lactose (Glucose + Galactose) from diet (e.g. breastfeeding to soy formula feeding) Note - More mild form (isolated late-onset cataracts) due to Galactokinase deficiency causing build up of Galactitol (osmotic agent)
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Mechanism of osmotic damage (cataracts, retinopathy, peripheral neuropathy) in hyperglycemia.
GLUCOSE = SORBITOL (BY ALDOSE REDUCTASE) Schwann cells, retina, and kidneys lack Sorbitol Dehydrogenase to convert Sorbitol to Fructose for removal from cell.
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Bloating Cramps Flatulence Osmotic diarrhea Acidic stool Increased breath hydrogen content Biopsy shows loss of brush border if secondary (not congenital)
LACTASE DEFICIENCY
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Urea cycle intermediates - Used to dispose NH3 and form Fumarate for TCA
Mitochondrial: CO2 + NH3 = Carbamoyl P (Carbamoyl Pase I) Ornithine + Carbamoyl P = Citrulline Cytosol: Citrulline + Aspartate = Argininosuccinate = Fumarate + Arginine Arginine = Urea + Ornithine Note - First step decreased in patients with liver disease (hyperammonemia)
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Transport of ammonium between muscle and liver. Note - Transamination requires B6
Amino acids + a-Ketoglutarate = Glutamate Glutamate + Pyruvate = a-Ketoglutarate + Alanine Alanine transferred to liver Alanine + a-Ketoglutarate = Pyruvate + Glutamate Pyruvate to Glucose for transport back to muscle Note - a-Ketoglutarate levels depleted in hyperammonemia (e.g. hepatic encephalopathy)
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Cori cycle.
Lactate from muscle moved to liver and converted to Glucose (with ATP) for movement back to muscle.
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``` Tremor (asterixis) Slurred speech Vomiting Blurring vision Somnolence Cerebral edema ```
HYPERAMMONEMIA Excess NH3 depletes a-Ketoglutarate, inhibiting TCA. Limit dietary protein Rifaximin to decrease colonic bacterial production Lactulose to acidify GI tract and trap NH4+ Benzoate, Phenylacetate, Phenylbutyrate to bind NH4+ If urea cycle deficiency also consider Arginine
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Developmental delay Intellectual disability Poorly regulated respiration and body temperature Poor feeding
N-ACETYLGLUTAMATE SYNTHASE DEFICIENCY CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY Both prevent conversion of NH3 to Carbamoyl Phosphate
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Clinical signs of hyperammonemia Decreased BUN Elevated orotic acid in blood and urine
ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY X-linked recessive build up of Carbamoyl phosphate converted to Orotic acid (pyrimidine synthesis)
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Cause of albinism.
TYROSINASE DEFICIENCY Deficient conversion of DOPA to Melanin.
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``` Intellectual disability Growth retardation Seizures Musty body odor Hypopigmentation ```
PHENYLKETONURIA Deficient Phenylalanine Hydroxylase - Tyrosine deficiency and buildup of Phenylketones in urine ``` Avoid Phenylalanine (Aspartame) Tyrosine becomes essential ``` Note - Hypopigmented catecholaminergic areas (e.g. locus coeruleus) Note - Similar presentation with Dihydrobiopterin Reductase deficiency which is required for both Phenylalanine Hydroxylase and Tyrosine Hydroxylase
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``` Severe CNS defects Intellectual disability Irritability Vomiting Poor feeding Urine smells like burnt sugar ```
MAPLE SYRUP URINE DISEASE Deficient a-Ketoacid Dehydrogenase (B1) blocks degradation of branched amino acids (Isoleucine, Leucine, Valine) - Buildup of a-ketoacids in the blood. Dietary limitation Thiamine (B1) supplementation
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Bluish-black connective tissue and sclerae Urine turns black on exposure to air Debilitating arthralgia in adulthood
ALKAPTONURIA Deficient Homogentisate Oxidase blocks degradation of Homogentisic acid (from Tyrosine) to Fumarate (for TCA)
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``` Intellectual disability Early thrombosis/atherosclerosis Marfanoid body habitus Lens subluxation (downward) Osteoporosis Kyphosis ```
HOMOCYSTINURIA Cystathionine Synthase deficiency (increased Methionine) - Treat with Methionine restriction/B6 Methionine Synthase deficiency (increased Cysteine) - Treat with Methionine/B12 Note - Methionine is turned into SAM
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Recurrent precipitation of hexagonal cystine stones.
CYSTINURIA Hereditary defect of renal PCT and intestinal amino acid transporters preventing reabsorption of Cystine, Ornithine, Lysine, and Arginine ("COLA"). Confirm with urinary cyanide-nitroprusside test ``` Urinary alkalinization (K Citrate, Acetazolamide) Chelating agents (Penicillamine) ```
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Derivative of Phenylalanine
Tyrosine = DOPA (=Melanin) = Dopamine = NE (requires Vit C) = Epi (requires SAM)
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Derivative of Tryptophan
Niacin | Serotonin = Melatonin
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Derivative of Glycine
Porphyrin = Heme
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Derivative of Glutamate
GABA | Glutathione
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Derivative of Arginine
Creatinine Urea Nitric Oxide
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Mechanism of Carbidopa
Inhibition of DOPA decarboxylase - required for conversion of DOPA to dopamine.
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Mechanism of Cortisol
Increased conversion of NE to Epi.
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Degradation of NE
Vanillylmandelic acid (with COMT)
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Degradation of Dopamine
Homovanillic acid
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Regulation of Glycogen Synthase
Insulin binds TKR which activates Protein Phosphatase Inhibited by PKA
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Regulation of Glycogen Phosphorylase
Activated by Glycogen Phosphorylase Kinase Inactivated by Protein Phosphatase Note - Inhibited by ATP/G-6-P, Promoted by AMP (muscle)
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Activation of Glycogen Phosphorylase Kinase
Liver: Epi/Glucagon activate Adenylate Cyclase Increased cAMP activates PKA Phosphorylation of Glycogen Phosphorylase Kinase Muscle (no Glucagon receptors): Muscle contraction increases Ca release from ER Ca activates Glycogen Phosphorylase Kinase
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Glycogen stain (e.g. Whipple disease).
Periodic acid-Schiff
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``` Severe fasting hypoglycemia Hepatomegaly with steatosis Lactic acidosis Hyperlipidemia Hyperuricemia ```
VON GIERKE DISEASE (TYPE I GLYCOGEN STORAGE DISEASE) Deficiency in Glucose-6-Phosphatase Deficient breakdown of G-6-P to Glucose Liver and kidney involvement Requires frequent oral glucose
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Normal glucose General hypotonia Cardiomegaly Exercise intolerance
POMPE DISEASE (TYPE II GLYCOGEN STORAGE DISEASE) Deficiency in lysosomal Acid Maltase (a-1,4-Glucosidase)
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``` Ketotic hypoglycemia Hepatomegaly without steatosis Hypotonia and weakness "limit dextrin" in cytosol Normal lactate ```
CORI DISEASE (TYPE III GLYCOGEN STORAGE DISEASE) Deficiency in Debranching Enzyme (a-1,6,-Glucosidase) Liver and muscle involvement
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``` Painful muscle cramps with normal lactate Increased glycogen in muscle Myoglobinuria with exercise Normal blood glucose (liver) Arrhythmia (electrolyte abnormalities) "Second wind" phenomenon during exercise ```
MCARDLE DISEASE (TYPE V GLYCOGEN STORAGE DISEASE) Deficiency in skeletal muscle Glycogen Phosphorylase (Myophosphorylase)
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``` Episodic neuropathic pain Angiokeratomas Hypohidrosis CKD CAD CVD ```
FABRY DISEASE Lysosomal storage disease - Deficiency of a-Galactosidase A causes build up of Ceramide trihexoside
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``` Lipid laden macrophages ("crumpled tissue paper") Hepatosplenomegaly Pancytopenia Osteoporosis Aseptic necrosis of femur Bone crises ```
GAUCHER DISEASE Lysosomal storage disease - Deficiency of Glucocerebrosidase causes build up of Glucocerebroside in lysosomes
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``` Foam cells (lipid laden macrophages) Hepatosplenomegaly Hypotonia Progressive neurodegeneration Cherry red macula ```
NIEMANN-PICK Lysosomal storage disease - Deficiency of Sphingomyelinase causes build up of Sphingomyelin
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``` Onion skin lysosomes No hepatosplenomegaly Developmental delay Progressive neurodegeneration Cherry red macula ```
TAY-SACHS DISEASE Lysosomal storage disease - Deficiency of Hexosaminidase A causes buildup of Ganglioside
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Globoid cells Peripheral neuropathy Developmental delay Optic atrophy
KRABBE DISEASE Lysosomal storage disease - Deficiency of Galactocerebrosidase causes build up of Galactocerebroside
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Central and peripheral demyelination Ataxia Dementia
METACHROMATIC LEUKODYSTROPHY Lysosomal storage disease - Deficiency in Arylsulfatase A causes buildup of Sulfatides
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``` Developmental delay Dwarfism Abnormal facies Hepatosplenomegaly Airway obstruction Corneal clouding ```
HURLER SYNDROME Sulfate accumulation due to Iduronidase deficiency
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Hurler syndrome with aggression and normal corneas.
HUNTER SYNDROME X-linked recessive
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Fatty acid synthesis shuttle.
CITRATE SHUTTLE Moves Citrate into cytoplasm Forms Acetyl-CoA via ATP Citrate Lyase Forms Malonyl-CoA via Acetyl-CoA carboxylase (+Biotin) Note - Last step is rate-limiting and upregulated with Insulin
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Fatty acid degradation shuttle.
CARNITINE SHUTTLE Moves Fatty Acyl-CoA into mitochondria Forms Acetyl-CoA via b-oxidation (Ketones, TCA) Note - Malonyl-CoA inhibits this shuttle to prevent b-oxidation of newly synthesized fatty acids
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Weakness Hypotonia Hypoketotic hypoglycemia
SYSTEMIC PRIMARY CARNITINE DEFICIENCY Defect in transport of LCFA into mitochondria resulting in toxic accumulation.
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``` Fasting child with... Hypoketotic hypoglycemia Liver dysfunction/Hyperammonemia Vomiting Lethargy Seizures Coma ``` Minor illness may lead to sudden death
MEDIUM CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY Inability to break down Fatty Acids into Acetyl-CoA - Buildup of Fatty Acylcarnitines in blood. Avoid fasting Note - If KETOTIC hypoglycemia consider Propionyl CoA Carboxylase / Methylmalonyl CoA Mutase deficiencies (elevated urine Propionic acid) - Inability to break down protein into Succinyl-CoA
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Mechanism of ketoacidosis.
Alcohol dehydrogenase depletes NAD+ - Decreased conversion of Malate to Oxaloacetate / Lactate to Pyruvate Oxaloacetate is required for conversion of acetyl-CoA to Citrate Buildup of acetyl-CoA, shunting FFA and Glucose towards production of Ketones for use by skeletal muscle Acetoacetate gives fruity odor to breath and is detected by urine test (b-hydroxybutyrate is not)
189
Fed state energy supply.
Glycolysis and aerobic respiration. Insulin promote storage of glycogen, fat, and protein.
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Fasting stage energy supply.
Hepatic glycogenolysis. Glucagon and Epi stimulate use of glycogen reserves - Glucagon functions at the liver, while Epi functions at the Kidneys, Muscles, and Adipose tissues
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Starvation (1-3 d) energy supply.
``` Hepatic glycogenolysis (depleted by day 1) Hepatic gluconeogenesis from peripheral Lactate and Alanine ``` Adipose release of FFA Muscle/liver shift use to FFA Hepatic mobilization of Triglycerides (hormone sensitive lipase) Converts FFA to Ketones via b-Oxidation Converts Glycerol to Glucose via Glycerol Kinase (DHAP) RBCs cannot use ketones (no mitochondria).
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Starvation (> 3 d) energy supply.
Adipose stores primary source of energy Brain begins using ketones Eventually protein degradation results in organ failure
193
Rate limiting step of cholesterol synthesis.
HMG COA = MEVALONATE By HMG CoA reductase Feedback inhibited by Glucagon and Cholesterol Feedback activated by Insulin and Thyroxine Note - HMG-CoA Synthase converts Acetoacetyl-CoA to HMG-CoA, which can also form Ketones via HMG-CoA Lyase
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Function of chylomicrons.
Dietary TGs to peripheral tissues via LPL (Insulin) Cholesterol remnants to liver Contains Apo-B48, Apo-CII, Apo-E
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Function of VLDL.
Hepatic TGs to peripheral tissues. Contains Apo-B100, Apo-CII, Apo-E Note - Converted to IDL by LPL to deliver remaining TGs back to liver
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Function of LDL.
Hepatic cholesterol to peripheral tissues Contains Apo-B100 for binding to LDLR Note - Formed from IDL by Hepatic Lipase (HL)
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Function of HDL.
Peripheral cholesterol to liver Contains Apo-A1 (required for LCAT) Suppository for Apo-CII (required for LPL function) Suppository for ApoE (required for liver reuptake) Secreted by both liver and intestines Increased synthesis with EtOH
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Function and regulation of hormone sensitive lipase
Degradation of TGs stored in adipocytes during fasting Induced by Catecholamines, Glucagon, ACTH Inhibited by Insulin
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Function of LCAT (lecithin-cholesterol acyltransferase).
In the presence of ApoA, catalyzes esterification of HDL. Transferred to VLDL/IDL/LDL by CETP (cholesterol ester transfer protein).
200
``` Pancreatitis Hepatosplenomegaly Eruptive/pruritic xanthomas Lipemia retinalis No increased risk of atherosclerosis ``` Creamy layer in supernatant Elevated Cholesterol Elevated Chylomicrons Elevated TG
FAMILIAL HYPERCHYLOMICRONEMIA Autosomal recessive LPL or ApoC-II deficiency
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``` Premature atherosclerosis (may have MI < 20 y/o) Tendon (achilles) xanthomas Xanthelasmas ``` ``` Elevated Cholesterol (300-700) Elevated LDL ```
FAMILIAL HYPERCHOLESTEROLEMIA Autosomal dominant LDLR or Apo-B100 deficiency
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Coronary artery disease Acute pancreatitis Elevated VLDL Normal LDL Elevated TG (> 1000)
FAMILIAL HYPERTRIGLYCERIDEMIA Autosomal dominant LPL deficiency
203
Mechanism of hyperhomocysteinemia. Note - Independent risk factor for thrombotic events
Deficient methyl-THF reductase enzyme Decreased conversion of THF to methyl-THF Uncouples Folate and Methionine cycles Normally with Methionine Synthase (B12)... Methyl-THF + Homocysteine = THF + Methionine Note - Cells require THF form of folate
204
Mechanism of E. coli lactose metabolism
LacI constitutively produces repressor protein Lactose leads to conformational change in repressor protein Repressor is released from operator region (minimal transcription) Decreased glucose removes inhibition of adenylate cyclase Increased cAMP activates cAMP-CAP which binds upstream to promoter region (maximal transcription) Increased transcription of Lac Z (b-galactosidase), Y (permease), and P (binding site for RNA polymerase)
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Premature atherosclerosis Palmar xanthomas Elevated Chylomicrons Elevated VLDL remnants
FAMILIAL DYSBETALIPOPROTEINEMIA Autosomal recessive ApoE mutation
206
Reactions limited to... Cytosol Mitochondria Both
Cytosol: Glycolysis, HMP shunt, Fatty acid synthesis Mitochondrial: TCA, Acetyl-CoA production, Oxidative phosphorylation, b-Oxidation, Ketogenesis Both: Urea, Heme, Gluconeogenesis
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``` Failure to thrive Developmental delay Megaloblastic anemia refractory to B12/Folate Orotic acid in urine No hyperammonemia ```
OROTIC ACIDURIA Autosomal recessive mutation in UMP synthase - inability to convert orotic acid to UMP in pyrimidine synthesis Treat with Uridine monophosphate (bypass enzyme)
208
Fastest metabolized sugar
FRUCTOSE F-1-P is converted by Aldolase B to DHAP/Glyceraldehyde which can enter as Glyceraldehyde-3-P (to Pyruvate) Note - This bypasses the major rate limiting step of Glycolysis
209
Effect of Glucagon on pancreas
Increases Insulin secretion for glucose utilization Note - Insulin decreases Glucagon release
210
Axonal transport direction of... Dynein Kinesin
Retrograde | Anterograde
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Probability of 2 allele from separate foci appearing together
Occurrence rate (allele 1) x Occurrence rate (allele 2) If observed frequency is greater than predicted there is linkage disequilibrium due to close proximity
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Initiation of transcription
RNA Pol II binding to CAAT/TATA in promoter Activator binding Enhancing region (location varies) Interaction of Activator with RNA Pol II Note - RNA Pol I makes rRNA, and RNA Pol III makes tRNA
213
Codes for border of a splice site
5'-GU...AG-3'
214
Genetic mutation found in multiple offspring but not in either parent
GERMLINE MOSAICISM Unlike somatic mosaicism is inherited by offspring
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Progressive spastic diplegia Growth delay Abnormal movements Note - Normal BUN
ARGINASE DEFICIENCY Elevated Arginine
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Calories per gram from... Protein Carbohydrates Fat
4 4 9
217
Enzymes required in Purine synthesis... Orotic acid + PRPP = UMP UDP = dUDP + CTP dUMP + THF = dTMP
Dihydroorotate dehydrogenase Ribonucleotide reductase Thymidylate synthase
218
Enzyme required for Pyrimidine synthesis... | PRPP = IMP = AMP + GMP
Inosine Monophosphate Dehydrogenase
219
Gene mutation responsible for... Orthostatic hypotension Impaired tear formation Reduced sensitivity to pain
FAMILIAL DYSAUTONOMIA IKAP loss of function
220
Eukaryotic translation
initiated when the small ribosomal subunit binds the 5' cap of mRNA and scans for the methionine start codone eIF (euk. initiation factors) facilitate this
221
How does eukaryotic translation differ during apoptosis
activation of eIF degradation leads to interruption of translation as a result alternative method of internal ribosome entry is used. Distinct nucleotide sequence called the internal ribosome entry site (IRES) attracts the eukaryotic ribosome to mRNA and allows translation to begin in the middle of the mRNA sequence
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initiation seq in euk translation | initiation seq in prok translation
kozak consensus sequence | shine Dalgarno sequence

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