KAPLAN_USMLE_STEP_1_LECTURE_NOTES_2018_BIOCHEMISTRY_and_GENETICS

enhancers in, 77 eukaryote genes, 40

eukaryote mRNA processing, 41, 42, 45 mutations in splice sites, 52, 53 prokaryote lack of, 38

splicing via snRNA, 34

Inversions of chromosome segments, 362–363

Iron

deficiency, 277, 278 excretion, 279, 280 heme synthesis, 276

hemochromatosis, 278, 314, 315–316, 318, 338

transport and storage, 278–279 Isochromosomes, 364

Isocitrate dehydrogenase, 194 Isoleucine, 123

Isotretinoin as teratogenic, 154

J

Jaundice, 281

K

Karyotype, 347–349 special karyotyping, 365

Keloid formation, 64 Kernicterus, 280, 281 Ketoacidosis, 249, 250, 252 Ketogenesis, 250 Ketogenolysis, 250 Ketones

acetyl-CoA as source, 168, 213, 244, 245, 249

brain use of, 168, 171, 249, 251 hypoglycemia and, 213, 244 ketogenesis, 250 ketogenolysis, 250, 251

liver synthesizing, 167, 168, 244, 250 metabolic energy in kcal/gm, 168 muscle metabolism, 170 postabsorptive state, 167, 249 prolonged fast, 168, 171, 249, 250, 251

Kidney

atrial natriuretic factor, 139 calcium homeostasis, 152, 153, 154 fructose metabolism, 186 glycogen storage, 205

urea excretion, 265, 266, 267 Kinases vs. phosphatases, 213

Kinetics of enzymes cooperative enzymes, 127–128

inhibitors and activators, 126–127 Lineweaver-Burk equation, 126 Michaelis-Menten equation, 124–125 reaction energy vs. rate, 124 transport kinetics, 128, 176–177, 179

Klein-Waardenburg syndrome, 82 Klinefelter syndrome, 351

nondisjunction and, 352–355

Km

glucose transport, 181 glycolysis, 179

inhibitors and activators, 126–127 Lesch-Nyhan syndrome, 297 Lineweaver-Burk equation, 126 Michaelis-Menten equation, 124–125 PRPP synthetase mutations, 296 transport kinetics, 128, 176–177, 179

Knockdown gene expression, 99 Knockout gene expression, 99 Krebs cycle. See Citric acid cycle

Kwashiorkor, 123

L

Lactase deficiency, 184, 185 Lactate

anaerobic glycolysis, 178, 180, 198 conversion to acetyl-CoA, 214 extreme exercise and alcohol, 215 gluconeogenesis, 211, 212, 213 glucose from, 214

glycogen metabolism, 205, 206 urate competition, 296

Lactate dehydrogenase gluconeogenesis, 213 glycolysis, 178, 180

Lactose, 184

lactose intolerance, 185 Lagging strand of DNA, 21–22, 24

Large segment deletion mutations, 51, 52 LDL (low-density lipoproteins), 229,

231–232 atherosclerosis, 233–234

density among lipoproteins, 228 receptor deficiency, 236, 306, 336 type IIa hyperlipidemia, 235

Lead poisoning, 276, 278

Leading strand of DNA, 21–22, 24 Leber hereditary optic neuropathy, 200,

313

Lecithin–cholesterol acyltransferase (LCAT), 233

Leigh syndrome, 197

Lesch-Nyhan syndrome, 295, 296–297 RFLP analysis, 397

as X-linked recessive, 308, 397 Leucine, 123

Leucine zipper binding domains, 78 Liability for disease, 371–372, 375

heritability and, 376

recurrence risks for multifactorial diseases, 374

Lineweaver-Burk equation, 126 inhibitors and activators, 126–127

Linkage analysis

gene mapping, 382–386 LOD scores, 385–386

online gene and marker maps, 380 polymorphic markers for, 379–381

Linked vs. unlinked genes, 382–383

LOD scores, 385–386 Linoleic acid, 223 Linolenic acid, 223 Lipid digestion, 224, 229

Lipid-soluble hormones, 135–136, 144 Lipid-soluble vitamins, 152–160 Lipoprotein lipase, 230, 235

deficiency, 235, 236

insulin inducing, 230, 235, 236 Lipoproteins

atherosclerosis, 233–234 cholesterol metabolism, 237–238 densities of, 228 glycerophospholipids, 227 hyperlipidemias, 235–236 hypolipidemias, 236–237 metabolism of, 229, 230 structure, 228

as triglyceride transport, 169, 226, 227, 228, 229, 230

Liver

aminotransferases, 266, 267 bilirubin and jaundice, 281 cholesterol, 231–232, 237 fuels preferred by, 168 gluconeogenesis, 213 glucose transport, 176, 177 glucose-6-phosphatase, 213 glycogen storage, 205 glycogen synthesis, 205 glycolysis, 179, 181

hepatic glycogen phosphorylase deficiency, 209, 211

hexose monophosphate shunt, 217 ketogenesis, 167, 168, 244, 250 lipid digestion, 224

lipoprotein metabolism, 229, 230, 231 metabolic postabsorptive state, 165,

167, 245

metabolic prolonged fast, 168 metabolic well-fed state, 165, 166,

168, 169

metabolism overview, 168–169 protein catabolism, 265 steatosis, 215, 226

triglyceride formation, 226

urea cycle, 265, 266, 267, 268–269 Locus, 303

centimorgan, 385 genotype, 303, 304

genotype frequencies, 333–334 imprinting, 320

locus heterogeneity, 316–317, 386 modifier loci, 314 polymorphism, 303–304

LOD (log of the odds) scores, 385–386 Long-chain acyl-CoA dehydrogenase

(LCAD) deficiency, 396

Index

Loss-of-function mutations, 304 Lymphomas, 358

Lysine, 123

Lysosomal α1,4-glucosidase deficiency, 209–210

Lysosomal enzymes I-cell disease, 63

posttranslational modification, 60, 61, 62, 63, 68

protein breakdown, 122 sphingolipid genetic deficiencies,

254–256

M

M phase (mitosis), 4, 19

Macrophages and atherosclerosis, 233, 234

vitamin E, 234 Malaria

heterozygote resistance and, 218, 338, 340

red blood cells as protection, 53, 218, 338

Malate shuttle, 182, 195, 213 Malic enzyme, 225 Malnutrition

folate deficiency, 275 kwashiorkor vs. marasmus, 123 metabolic starvation, 168 vitamin K deficiency, 159

Manifesting heterozygotes, 310 Mannose phosphorylation, 60, 61, 62, 63 Mantle cell lymphoma, 358

Maple syrup urine disease, 119, 270, 271, 337

Marasmus, 123

Marfan syndrome, 272, 306 pleiotropy of, 316

STRP indirect genetic diagnosis, 395 Mature-onset diabetes of the young

(MODY), 181

McArdle disease, 209, 210–211 Medium chain acyl-CoA

dehydrogenase (MCAD) deficiency, 246, 247, 248

Megaloblastic anemia orotic aciduria, 291

tetrahydrofolate deficiency, 150, 273, 275, 291

vitamin B12 deficiency, 150, 248, 274,

275, 291

Meiosis

crossover, 51, 52, 382–386 inverted chromosomes, 362 nondisjunction and aneuploidy,

352–355, 360 pseudoautosomal regions, 303 reciprocal translocations, 356–358 recombination mapping, 382–386

415

processing by eukaryotes, 40–42 processing by prokaryotes, 38 prokaryote production, 38–39, 45 RNA editing, 44

RNA interference, 99–100 transcription and translation, 36, 49 transcription base sequence, 37 translation, 49, 55–57

Multifactorial diseases, 371–376 liability, 371–372, 374

male vs. female, 373 neural tube defects, 375 obesity, 371–372 principles of, 375–376 recurrence risks, 374–375 threshold, 372–373

Muscle. See Cardiac muscle; Skeletal muscle

Muscle glycogen phosphorylase deficiency. See Myophosphorylase deficiency

Mutations, 51–52, 304–305 allelic heterogeneity, 271, 297, 314 balanced vs. unbalanced, 355 delayed age of onset, 317–318 deletion, 361. See also Deletion

mutations DNA repair, 25–27

DNA repair and diseases, 27–28

DNA replication errors, 25, 27, 51,

53, 318

dominant vs. recessive, 303

enzyme Michaelis-Menten plots, 125 founder effect, 337, 339

frameshift, 51, 52, 304 gain-of-function, 304, 318 galactosemia, 185 glucokinase gene, 181 incomplete penetrance, 315–316 in-frame, 51, 304

insertion, 304 Leigh syndrome, 197 loss-of-function, 304

missense, 51, 52, 125, 181, 304, 314 mitochondrial DNA, 200, 313

new mutations, 317, 337 nonsense, 51, 52, 304, 314 oncogenic, 143 penetrance, 311, 315–316 pleiotropy, 316

point, 51, 62

polymerase chain reaction, 112–113 protein abnormality from, 40 PRPP synthetase and Km, 296 silent, 51, 52

in splice sites, 52, 53 transition mutations, 51 transversion mutations, 51 types of, 304

variable expression, 314

X-linked recessive in females, 310

Myocardial infarction homocystinemia, 272 hypercholesterolemia, 236 hypoxia, 198

troponin levels and, 198 Myoclonic epilepsy with ragged red

muscle fibers, 200, 313 Myoglobin

heme synthesis, 275–279 myoglobinuria, 210, 238, 247, 276

Myopathic CAT/CPT deficiency, 246, 247

Myophosphorylase deficiency, 209, 210–211

Myotonic dystrophy anticipation in, 319, 393

as autosomal dominant, 319 RFLP analysis, 393–394

as trinucleotide repeat expansion disease, 53

N

NADH

accumulation and citric acid cycle, 200 aerobic glycolysis, 179, 182

alcohol and gluconeogenesis, 214–215 anaerobic glycolysis, 180 β-oxidation, 245–249

citric acid cycle, 193–195 electron transport chain, 195–200 glycolysis, 178, 180, 182 metabolism overview, 163, 164 P/O ratios, 198

pyruvate dehydrogenase, 188 NADPH

cholesterol synthesis, 237 functions of, 216

hexose monophosphate shunt, 216–218 hydrogen peroxide, 200

malic enzyme, 225 tetrahydrofolate, 273 Natural selection, 337–338

Negative nitrogen balance, 123 Neural tube defects, 275, 375 Neurofibromatosis type 1, 306 as autosomal dominant, 384

recombination frequency, 384–385 Neutrophils

hexose monophosphate shunt, 217 polymorphonuclear neutrophils, 199,

216, 217 Newborns

galactosemia, 185 glucokinase deficiency, 181 gray baby syndrome, 58

hereditary fructose intolerance, 187 Lesch-Nyhan syndrome, 297

maple syrup urine disease, 271 PCR for HIV testing, 114 phenylketonuria, 271 physiologic jaundice, 281 Pompe disease, 209–210

Rh disease, 281

vitamin K deficiency, 158, 159 NFkB (nuclear factor kappa-B), 78 Niacin (vitamin B3), 150

hyperlipidemia treatment, 151, 243 pyruvate dehydrogenase, 188

Niemann-Pick disease, 255 Nitric oxide, 139–140 Nitrogen balance, 123 Nitrogen excretion, 265–269 Nomenclature

chromosomes, 349 cytogenetics, 347–349 fatty acids, 223–224 genetics, 303–305

“–in” as oxidized and colored, 276 nucleic acids, 5–7

“–ogen” as colorless, 276 pedigrees, 305

Noncompetitive inhibitors, 126–127 Nondisjunction and aneuploidy,

352–355

Down syndrome, 352–355, 360 maternal age and, 352–353

Non–insulin-dependent diabetes mellitus, 252

Nonobstructive azoospermia, 311 Nonsense mutations, 51, 52, 304

allelic heterogeneity, 314

Normal curve for liability for disease, 371–372, 373, 375

Northern blot, 104, 107 alternative splicing, 42

N-terminal hydrophobic signal sequence, 60, 61, 62

Nucleases, 18

DNA repair, 25–26

DNA vs. RNA synthesis, 20 exonucleases, 18, 20, 21 nucleosomes and, 11 purine catabolism, 295

See also Endonucleases

Nucleic acids

nucleotide structures, 5–7 polymers of nucleotides, 7–10 recombinant DNA, 87–88

See also DNA; RNA

Nucleolus, 12, 43

Nucleosides, 6–7 Nucleosomes, 11–12 Nucleotides, 5–7, 289

codons, 49

DNA vs. RNA synthesis, 20–21 excision repair, 25, 27

Index

hexose monophosphate shunt and, 216–217

mRNA base sequence, 37 RNA editing, 44

single nucleotide polymorphisms, 380, 381

synthesis, 289–290 transcription, 35–36

trinucleotide repeat expansion, 51, 53

O

O2

oxidative phosphorylation, 195–200 oxidative phosphorylation regulation,

200

reactive oxygen species, 199–200, 216, 218, 233, 277

See also Aerobic glycolysis

Obesity

clinical definition of, 372 liability for, 371–372 threshold for, 372

Okazaki fragments, 21, 22, 23, 24 Oligomycin (F0), 199

Omega-3 fatty acids, 223 Oncogenes, 83, 357, 358

One-carbon units, 273–275

Online gene and marker maps, 380 Oogenesis

imprinting, 320 nondisjunction and aneuploidy,

352–355

X inactivation, 309

Ornithine transcarbamoylase, 268 deficiency, 269, 273, 308

Orotic aciduria, 291 Osteogenesis imperfecta, 64, 66

locus heterogeneity, 317 Osteomalacia, 152, 154 Ova, 303

age and Down syndrome, 352–353 as haploid, 303, 349 mitochondrial contribution, 313 mutation transmission, 304 translocation carriers, reciprocal,

356–357

translocation carriers, Robertsonian, 358–360

Oxidative phosphorylation, 195–200 aerobic glycolysis, 179

Leigh syndrome, 197

proton gradient, 196, 197–198 regulation, 200

P

Palindromes in DNA, 89–90, 100 Palmitate synthase, 224, 225–226 Palmitic acid, 223, 225, 226

417

Posttranslational modification, 60, 61, 62–67, 68

glycosylation of proteins, 120 Potassium levels and diabetic

ketoacidosis, 252

Prader-Willi syndrome, 83, 321, 322, 361 FISH to detect, 365

Pregnancy

Down syndrome prenatal testing, 353, 360

folate deficiency, 150, 272, 273, 275, 375 genetic testing, 106–107

isotretinoin as teratogenic, 154 neural tube defects and folate, 275, 375 phenylkentonuric mothers, 271 positive nitrogen balance, 123, 125 prenatal genetic diagnosis, 398 reciprocal translocation carriers,

356–357 Preimplantation diagnosis, 398 Pre-mRNA, 41, 42, 45 Prenatal genetic diagnosis, 398 Prevalence of disease

male vs. female, 373, 374 of obesity, 372

population prevalence, 375

Primary protein structure, 58 Probability of events, 335

LOD scores, 385–386 Proband, 305

Probe DNA, 104

allele-specific oligonucleotide probes, 391–392

cDNA for, 100, 104

fluorescence in situ hybridization (FISH), 365

gene expression profiling, 107 Northern blot, 104, 107 Southern blot, 10, 104, 105 special karyotyping, 365 Western blot, 104, 108

Proinsulin, 63, 83, 181 Prokaryotes

ADP-ribosylation by toxins, 143–144 ammonia production, 265, 266, 267 antibiotics and vitamin K, 158 bilirubin to urobilinogen, 279, 280 DNA replication, 18, 21–22, 23 DNA supercoiling, 10

mRNA production, 38–39, 45 protein synthesis inhibitors, 58 restriction endonucleases, 89 RNA polymerases, 35, 38 rRNA into ribosomes, 43

start and stop codons, 68 transcription and translation, 38–39,

55, 68

Prolonged fast (starvation), 168, 169, 170, 171

brain, 165, 168, 171, 249, 250, 251 ketone body metabolism, 168, 171,

249, 250, 251

red blood cells, 165, 168 Promoters

chromatin remodeling, 75 eukaryotic mRNA production, 40, 45 general transcription factors, 78–79 genomic vs. cDNA libraries, 93 prokaryotic mRNA production, 38,

39, 45

transcription, 33, 34, 35, 36 upstream promoters, 76–77

Proofreading of DNA repair, 20, 21, 22 cell cycle and, 27

reverse transcriptase lack of, 23 Propionic acid pathway, 248–249, 271 Propionyl-CoA carboxylase, 248, 249,

270

deficiency, 270, 271–272 Proteasomes, 60, 122 Protein kinases, 136–142 Proteins

abnormalities via mutations, 40. See also Mutations

ADP-ribosylation, 143–144 alternative splicing of pre-mRNA, 42 brain use in fasting states, 251 folding and subunits, 58–59

folding chaperones, 59 folding defects, 60, 62 gene definition, 3, 303

gene expression vs. DNA replication, 3–5

metabolic energy in kcal/gm, 168 metabolic hydrolysis, 164, 167 metabolic postabsorptive state, 167 metabolic prolonged fast, 168, 265 metabolic recommended diet, 168 metabolic well-fed state, 166 monocistronic vs. polycistronic, 39 posttranslational modification, 60, 61,

62–67

prokaryotic production, 38–39 protein turnover, 122–123 regulatory protein binding sites, 9 specific transcription factor classes,

78, 81

synthesis inhibitors, 56, 57, 58 synthesis via translation, 3, 36, 49,

54–57, 122

targeting for delivery, 60–63, 68 toxins halting synthesis, 43 transcription of DNA, 36

Prothrombin, 157–158 Proton gradient, 196, 197–198

uncouplers, 196, 199 PRPP amidotransferase, 294

PRPP synthetase, 289, 290, 296

Index

Pseudoautosomal regions, 303

Pseudomonas toxins, 56, 57, 68 Punnett squares, 306, 307, 308, 312 Purines, 5–6, 8, 9

catabolism, 295–297 mutations, 51 synthesis, 273, 293–294

Pyridoxine. See Vitamin B6

Pyrimethamine and tetrahydrofolate, 292

Pyrimidines catabolism, 293 mutations, 51 nomenclature, 7 structure, 5–6, 8, 9 synthesis, 290–293

synthesis deficiencies, 269, 291 thymine dimer repair, 25–26

Pyruvate carboxylase, 212, 213 acetyl-CoA regulation of, 214, 245,

251

citrate shuttle, 225

Pyruvate dehydrogenase, 187–189 acetyl-CoA regulation of, 187–188,

214

fatty acid synthesis, 224 Pyruvate kinase

deficiency, 178, 183 gluconeogenesis, 212 glycolysis, 178, 180, 181

Q

Quaternary protein structure, 59 Quinolones, 22, 23

R

Ragged-red muscle fiber disease, 200, 313

Rate of reaction (v)

energy of reaction versus, 124 Lineweaver-Burk equation, 126 Michaelis-Menten equation, 124–125

Rate-limiters

allosteric inhibitors and activators, 165

cholesterol synthesis, 238 fatty acid synthesis, 225

glucagon vs. insulin, 142, 164–165,

206, 207, 211, 213 gluconeogenesis, 80 glycogen synthesis, 142, 205 glycogenolysis, 142, 207 glycolysis, 179, 186

heme synthesis, 275, 277

hexose monophosphate shunt, 216 oxidative phosphorylation, 200 vitamin D to calcitriol, 152

Reactions

cooperative enzymes, 127–128

419

nucleolus for assembly, 12, 43 prokaryotic translation, 38–39 prokaryotic vs. eukaryotic, 43, 45 rRNA forming, 34, 43

toxin effects on, 43

translation site, 49, 55, 56–57, 59, 61,

62, 122

tRNA for amino acids, 34, 43–44

Ribozymes, 34 Rickets, 152, 153, 154

Ring chromosome abnormality, 363 Risk factors for disease, 371

male vs. female thresholds, 373 See also Recurrence risk

RNA editing, 44

gene definition, 3, 303 repair, 21

reverse transcriptase, 23 reverse transcriptase PCR, 114 ribose pentose of, 5

structure of, 5–7, 9 synthesis, 20–21, 37, 273

transcription, 3, 33, 35–36. See also

Transcription

translation, 3, 49, 55–57. See also Translation

types of, 34–35

RNA interference (RNAi), 99–100 RNA polymerases, 34–35

DNA vs. RNA synthesis, 20–21 eukaryotes, 40, 41, 45 prokaryotes, 35, 38, 45 ribosome construction, 43 transcription, 33, 34–36 translation, 43

Robertsonian translocations, 349, 358–360

Rod cells and vitamin A, 155–156 Rough endoplasmic reticulum (RER)

collagen posttranslational modifications, 64–65

glycosylation of proteins, 61, 62, 120 misfolded proteins, 62

polysomes, 58

translation site, 59, 60, 61, 62 vitamin K–dependent carboxylation,

157–158

rRNA (ribosomal RNA), 34–35, 43 RNA editing, 44

S

S phase (mitosis), 4, 18, 19 DNA repair, 27

Saturated fatty acids definition, 223 Scavenger receptor (SR-B1), 233, 234 SCID (IL-receptor γ-chain deficiency),

308

Scurvy, 66, 68, 151

Secondary protein structure, 58 Secretions and delivery signals, 61–62,

63, 68 Serine, 120

Serotonin from tryptophan, 275 Severe combined immunodeficiency

(SCID), 296

Sex chromosomes, 303

allele frequencies and, 336–337 aneuploidy of, 351

karyotype, 347–349 number of genes, 347

Y chromosomes, 303, 311

See also X chromosomes

Shiga and Shiga-like toxins, 43, 56, 57, 68 Shine-Dalgarno sequence, 38, 39, 56,

57, 68

Short tandem repeats. See

STRPs (short tandem repeat polymorphisms)

Sickle cell disease

as autosomal recessive, 307 electrophoresis test, 122 genetic testing, 106–107 hemolytic crisis, 281 heterozygous for, 82, 338, 340

Sideroblastic anemia lead poisoning, 278

vitamin B6 deficiency, 277

Sigma (σ) factor

prokaryotic mRNA production, 38, 45 transcription, 34–35

Silencers of gene expression, 77 methylation of DNA, 83, 309 RNA interference, 99–100 specific transcription factors, 79

Silent mutations, 51, 52 Skeletal muscle

amino group removal, 265, 266, 267 anaerobic glycolysis, 177

glucose transport, 176, 177 glucose-6-phosphatase absence, 213 glycogen storage, 205

glycogen synthesis, 205

metabolic fuels preferred by, 168, 170, 189, 249

metabolic postabsorptive state, 165, 167, 245

metabolic prolonged fast, 168, 169, 250, 265

metabolic well-fed state, 165, 166, 168 metabolism overview, 170

protein catabolism, 265

ragged-red muscle fiber disease, 200 thiamine deficiency, 189

Slot (dot) blot, 104, 392 Slow-twitch muscle fibers, 170, 205

Smooth endoplasmic reticulum (SER), 226, 238

SNPs (single nucleotide polymorphisms), 380, 381

snRNA (small nuclear RNA), 34–35 eukaryote mRNA processing, 41, 42

Somatic cells, 303

Sonic Hedgehog (SHH), 82 Southern blot, 104, 105–107 myotonic dystrophy, 393–394

renaturation of DNA, 10 RFLPs and, 105–107, 381, 396

Special karyotyping, 365

Specific transcription factors, 78, 79 Sperm, 303

age and Down syndrome, 352 as haploid, 303, 349 mitochondrial contribution, 313 mutation transmission, 304

nonobstructive azoospermia, 311 translocation carriers, reciprocal,

356–357

translocation carriers, Robertsonian, 358–360

Spermatogenesis imprinting, 320

nondisjunction and aneuploidy, 352–355

pseudoautosomal regions, 303 Sphingolipids, 253–256

genetic deficiencies, 254–256 Sphingomyelin, 253, 254 Spina bifida, 375

Spinobulbar muscular atrophy, 53 Spliceosomes. See snRNA (small

nuclear RNA)

SRY gene, 311 Starvation, 168

See also Prolonged fast (starvation)

Statins

cholesterol synthesis, 237, 238

as competitive inhibitors, 126, 238 Statistics of events, 335

LOD scores, 385–386 Steroid receptors, 78, 81, 83

Stop codon from nonsense mutations, 51, 52, 304

STRPs (short tandem repeat polymorphisms)

indirect genetic diagnosis, 395 as informative markers, 394

as microsatellites, 108, 380, 381 polymerase chain reaction, 108–109,

111–112

polymorphic markers, 380, 381 Submetacentric chromosomes, 349 Substrate-level phosphorylation, 180 Succinate dehydrogenase, 195, 196, 197 Succinyl-CoA, 195

Sucrose metabolism, 186

Index

hereditary fructose intolerance, 186, 187

myophosphorylase deficiency and, 210–211

Sudden infant death syndrome (SIDS), 247

Superoxides as ROS, 199, 200

T

Tay-Sachs disease, 255, 307 Telecrine hormones, 135 Telomerase, 22–23

reverse transcriptase activity, 23 Telomeres, 349

Template strand DNA replication, 23

DNA vs. RNA synthesis, 21 transcription, 33, 35–36, 37

Teratogenicity of isotretinoin, 154 Terminators

prokaryotic mRNA production, 38, 39, 45

transcription, 33, 34, 35, 36, 45 Tertiary protein structure, 59, 120 Tetrahydrofolate (THF), 150, 273–274

antibiotics and, 292 deficiency, 150, 273 pyrimidine synthesis, 292

vitamin B12 deficiency and, 274 Tetraploid cells, 349, 350 α-Thalassemia, 52 β-Thalassemia, 40, 53

Thermogenin as uncoupler, 196, 199 Thiamine (vitamin B1), 150

citric acid cycle, 194 deficiency, 189

pyruvate dehydrogenase, 188 transketolase, 216

Thiazide diuretics and hyperuricemia, 296

Threonine, 120, 123

Threshold for multifactorial diseases, 372–373, 375

male vs. female, 373, 375 obesity threshold, 372

Thymidines, 273

Thymidylate synthase, 292, 293 Thymine, 5, 7, 9

thymine dimer repair, 25–26, 27 Topoisomerases

DNA-binding drugs, 9 supercoiling and, 11, 22, 23

Trans regulators, 77 Transaminases, 266, 267, 281 Transcription, 33, 35–36 alternative splicing, 42

in central dogma, 3 eukaryotic mRNA production,

40–42, 45

421

Uracil, 5, 7, 9

cytosine deamination repair, 27 Urea cycle, 265–266, 268–269

genetic deficiencies, 269 intestinal ammonia, 266, 267

Uric acid from purines, 295, 296 tumor lysis syndrome, 296 Uridine monophosphate (UMP)

synthase, 291, 292 deficiency, 291

Urine

bilirubin, 280, 281 hemolytic anemia and, 280 myoglobinuria, 210, 238, 247 nitrogen excretion, 265, 266 porphyrias, 276, 277

uric acid from purines, 295, 296 Uroporphyrinogen decarboxylase, 276

deficiency, 276, 277

V

Valine, 123

Variable expression, 314

of hemochromatosis, 315–316 incomplete penetrance versus, 315, 316

Variable number of tandem repeats.

See VNTRs

Vibrio cholerae ADP-ribosylation, 143 Virions and gene therapy vectors, 95

Viruses

antiviral RNA interference, 100 as gene therapy vectors, 94–95 viral hepatitis and jaundice, 281 viral load in AIDS patients, 114

Vision and vitamin A, 155–156 Vitamin A (carotene), 152, 154–157

as antioxidant, 234 deficiency, 152, 157 toxicity, 157

Vitamin B1 (thiamine), 150 citric acid cycle, 194 deficiency, 189

pyruvate dehydrogenase, 188 transketolase, 216

Vitamin B2 (riboflavin), 151 pyruvate dehydrogenase, 188

Vitamin B3 (niacin), 150 hyperlipidemia treatment, 151, 243 pyruvate dehydrogenase, 188

Vitamin B6 (pyridoxine), 151 aminotransferases and, 267 deficiency, 272, 277, 278 δ-aminolevulinate synthase (ALA)

and, 277

homocystinemia from deficiency, 272 Vitamin B9 (folate)

deficiency, 248, 272, 273, 275, 291, 375 homocystinemia from deficiency,

272, 275

metabolism, 274

neural tube defects and, 275, 375 pregnancy and, 150, 272, 273, 275, 375 tetrahydrofolate, 273–274

vitamin B12 deficiency versus, 275

Vitamin B12 (cobalamin), 150, 274–275 deficiency, 150, 248, 249, 253, 272,

274, 275, 291 homocystinemia from deficiency,

272, 275

N-methyl THF–homocysteine methyltransferase, 273

methylmalonyl-CoA mutase, 248, 249 vitamin B9 deficiency versus, 275

Vitamin C (ascorbate), 151 as antioxidant, 234

iron absorption, 279 scurvy, 66, 68, 151

vitamin K vs. C deficiency, 159

Vitamin D (cholecalciferol), 152–154 cholesterol required, 237 deficiency, 152, 154

toxicity, 154

Vitamin E (α-tocopherol), 152, 160 atherosclerosis and, 234 deficiency, 152, 160

Vitamin K, 152, 157–160 anticoagulant therapy, 160, 161 deficiency, 158–159

vitamin K vs. C deficiency, 159

Vitamins

homocystinemia from deficiency, 272, 275

lipid-soluble, 152–160 water-soluble, 149–151

Vitreous humor, 66

VLDL (very low-density lipoproteins), 229, 230, 231

density among lipoproteins, 228 glycerophospholipids, 227 hypertriglyceridemia, 235–236 structure, 228

triglyceride transport, 169, 226, 227, 229, 230

VLDL remnants. See IDL (intermediate-density lipoproteins)

Vmax

glycolysis, 179

inhibitors and activators, 126–127 Lineweaver-Burk equation, 126 Michaelis-Menten equation, 124–125 protein kinase activation, 137 transport kinetics, 128, 176, 179

VNTRs (variable number of tandem repeats), 106, 380, 381

Von Gierke disease, 209

Index

W

Warfarin, 160, 161 Water-soluble hormones

G proteins, 137–138, 143–144 insulin receptor, 140–141 lipid-soluble versus, 135–136 protein kinases, 136–140

Water-soluble vitamins, 149–151 Watson-Crick DNA, 9, 10

Well-fed (absorptive) state, 165, 166, 169

acetyl-CoA and regulation, 214 preferred fuels in, 168

Western blots, 104, 108 HIV, 108, 113–114

White muscle fibers, 170, 178, 180, 205 Williams syndrome, 361

Wilms tumor (WAGR), 361

X

X chromosomes, 303

allele frequencies and, 336–337 aneuploidies, 351

Barr bodies, 82, 83, 309–310 hemizygous for, 307–308, 336–337 karyotype, 347–349

manifesting heterozygotes, 310 number of genes, 347

X inactivation, 309–310

X-linked dominant diseases, 311, 312, 319

X-linked dominant inheritance, 311–312

X-linked recessive diseases, 308, 310, 397

X-linked recessive inheritance, 307–310, 336–337

Xanthine oxidase, 295, 296, 297 Xeroderma pigmentosum, 26, 27, 28,

314

XIST gene, 309

X-linked severe combined immunodeficiency, 98

Y

Y chromosomes, 303, 311 karyotype, 347–349 number of genes, 347 X inactivation, 309–310

Z

Z-DNA, 9

Zellweger syndrome, 79

Zinc finger binding domain, 78, 81