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Flashcards in Biochemistry Deck (326)
1

Which histone is not in the nucleosome core?

H1

2

Which makes DNA active and which makes it less: methylation and acetylation?

More active - acetylation, less active - methylation

3

Which bases are purines and which are pyrimidines?

Purines - AG, Pyrimidines - CUT

4

AAs required for purine synthesis

Glycine, Aspartate, Glutamine

5

AAs required for pyrimidine synthesis

Aspartate

6

Main branch point for both pyrimidine and purine synthesis

PRPP

7

What pathways is carbamoyl phosphate involved in?

De novo pyrimidine synthesis and the urea cycle

8

OTC deficiency

OTC involved in urea cycle. Leads to increase in carbamoyl phosphate which is converted to orotic acid (pyr and pur synthesis)

9

What does hydroxyurea inhibit?

Ribonucleotide reductase

10

Does each of the following inhibit purine or pyrimidine synthesis? 6-MP, 5-FU, MTX, Trimethoprim

6-MP is purine, the others are all pyrimidine

11

Defects that cause orotic aciduria (2) and the genetics

Orotic acid phosphoribosyltransferase or orotidine 5-phosphate decarboxylase. AR

12

How do we distinguish between orotic aciduria and OTC deficiency?

OTC deficiency includes signs of hyperammonemia (due to backflow into urea cycle). No hyperammonemia in orotic aciduria

13

Treatment for orotic aciduria

Uridine (inhibits carbamoyl phosphate synthase II)

14

ADA deficiency causes feedback inhibition of what enzyme?

Ribonucleotide reductase

15

What will be present in high levels in the blood and what enzyme will be hyperactive in Lesch-Nyhan?

Uric acid present in high levels (failure to salvage). PRPP will be hyperactive (must make all new purines)

16

Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

Lesch-Nyhan

17

Genetics of Lesch-Nyhan

X recessive

18

Prokaryotic DNA polymerases and their functions

DNA pol 3 - synthesizes 5 to 3, proofreads 3 to 5. DNA pol 1 - removes RNA primers 5 to 3.

19

Defect in xeroderma pigmentosum

Excision of thymine dimers (failure of nucleotide excision repair)

20

Give the actors in base excision repair in order

1) Glycosylase, 2) Endonuclease and lyase, 3) DNA pol, 4) Ligase

21

Defect in HNPCC

Failure of mismatch repair

22

Defect in ataxia telangiectasia

Failure of nonhomologous end joining (a type of DNA repair)

23

What direction is mRNA read? What direction does protein synthesis occur in?

mRNA read 5 to 3. Protein synthesis is N to C

24

mRNA stop codons and what are they recognized by?

UGA, UAA, UAG. Recognized by releasing factors

25

Common sequences in promoters

AT-rich (TATA, CAAT)

26

What do each of the eukaryotic RNA pols make?

RNA pol 1 - rRNA (in the nucleolus), RNA pol 2 - mRNA, RNA pol 3 - tRNA

27

What does alpha-amanitin (in death cap mushrooms) inhibit and what is the effect of this?

RNA pol 2. Causes liver failure

28

Which end are the cap and poly-A tail respectively put on in mRNA?

Cap is 5 prime, poly A tail is on 3 prime end

29

What steps of mRNA processing take place in the cytosol?

Addition of 7-MG to 5 prime cap and interaction with P bodies

30

What do snRPs do and what disease can include antibodies to them?

Form splicosome. SLE

31

What effect do lactose and glucose have on the lac operon respectively?

Lactose - inhibits the repressor (expression of lac operon), Glucose - inhibits the activator (no expression of lac operon)

32

What bacteria are notable for having the lac operon?

E coli

33

What sequence on tRNA holds the AA and which end of the tRNA is it on?

CCA on the 3 prime end

34

What drugs inhibit DNA gyrase (prokaryotic topoisomerase 2)?

Fluoroquinolones

35

What drugs bind 30S and prevent attachment of aminoacyl-tRNA?

Tetracyclines

36

What molecule is necessary for tRNA charging and what is necessary for tRNA translocation?

Charging - ATP, translocation - GTP

37

What drugs bind 30S and inhibit formation of initiation complex and cause misreading of mRNA?

Aminoglycosides

38

What drugs inhibit 50S peptidyl transferase?

Chloramphenicol

39

What drugs block translocation during translation?

Macrolides

40

What drugs block peptide bond formation during translation?

Clindamycin and chloramphenicol

41

What is the 16S subunit, what is it part of, and what does it do?

Part of 30S, contains a sequence complementary to mRNA for translation initiation

42

Rb and p53 inhibit transition from what to what?

G1 to S phase

43

Two examples of stable cells

Hepatocytes and lymphocytes

44

What type of muscle is not permanent (ie can divide)?

Smooth

45

What happens in RER and what cells have lots of RER?

Synthesis of exported proteins and N-linked oligosaccharide addition. Mucus-secretion goblet cells (SI) and plasma cells

46

What part of the neuron are nissl bodies in and what are they?

They are RER. In dendrites but not axons

47

What do SER do and give an example of something that would lead to more SER in liver

Steroid synthesis and detox of drugs and poisons. Polypharmacy will do it.

48

Protein modification in golgi

Modifies N-oligosaccharides on aspargine. Adds O-oligosaccharides on serine and threonine

49

Vesicular trafficking proteins (3) and what each does

COPI - retrograde (golgi to ER), COPII - anterograde (RER to cis-golgi), Clathrin - trans-golgi to lysosomes, PM to endosomes

50

Coarse facial features, clouded corneas, restricted joint movements

I-cell disease. Will see high plasma levels of lysosomal enzymes

51

Where are chondroiton and heparan formed and where does sulfation of tyrosine occur?

Golgi

52

Where are very long FAs beta oxidized?

Peroxisomes

53

Between dynein and kinesin, which is retrograde and which is anterograde?

Kinesin - anterograde, Dynein - retrograde

54

What drugs act on microtubules?

Mebendazole and Thiabendazole (antihelminthic), Griseofulvin (antifungal), Vincristine and vinblastine (anticancer), Paclitaxel (anti breast cancer), Colchicine (anti gout)

55

Kartageners is a defect in what?

Dynein arm

56

How do ciliated cells communicate?

Gap junctions

57

Infertility, bronchiectasis, sinusitis, situs inversus

Kartageners

58

What disease is glial fibrillary acid protein (GFAP) a marker for?

Alexander disease (17q21 mutation, developmental delay, macrocephaly, seizures, hydrocephalus, dementia, spasticity)

59

3 main methods of protein degradation

Proteosome (ubiquitin), Lysosome, Calcium-dependent enzymes

60

Give the cancer(s) associated with each of the stainable intermediate filaments

Vimentin - sarcomas and some carcinomas, Desmin - rhabdomyosarcoma, leiomyoma, Cytokeratin - carcinomas, some sarcomas, GFAP - astocytoma, Neurofilaments - adrenal neuroblastoma

61

Ouabain

Inhibits Na-K pump by binding to K site

62

What is the most abundant AA in collagen?

Glycine

63

Pattern in preprocollagen

Gly-X-Y (X and Y are proline, hydroxyproline or hydroxylysine)

64

Which step of collagen synthesis requires Vitamin C?

Hydroxylation of proline and lysine

65

Which steps of collagen synthesis occur where?

ER - synthesis, hydroxylation and glycosylation (triple helix formation), Extracellular - C-terminal cleavage (tropocollagen), Cross-linking (by lysyl oxidase)

66

What class of drugs inhibits collagen synthesis?

Steroids

67

Genetics of osteogenesis imperfecta

Type 1 - AD (most common). Type 2 - AR (fatal early)

68

Name a disorder that includes hearing loss and dental imperfections

Osteogenesis imperfecta

69

What is wrong with the type 3 collagen in ehlers-danlos?

Defective extracellular cleavage at the N and C termini makes it more soluble and less crosslinked

70

Genetics of Alport and what is the deficiency?

Abnormal type 4 collagen. X recessive

71

Hereditary nephritis, deafness, ocular disturbances

Alport. Ocular disturbances due to lenticonus (thinning of lens capsule)

72

What AAs are prevalent in elastin?

Proline and glycine (both nonglycosylated)

73

Wrinkles of aging are due to what?

Reduced collagen and elastin production

74

What type of emphysema is seen in a1 antitrypsin deficiency?

Panacinar

75

Give the targets of Southern, Northern, and Western blots. Briefly describe Southwestern blotting.

Southern - DNA, Northern - RNA, Western - Protein. Southwestern blotting finds TFs

76

Cre-lox system

Inducibly manipulating genes using antibiotic-controlled promoters

77

Heteroplasmy relates to what kind of DNA?

Mitochondrial

78

What chromosome contains the gene for Prader-Willi and Angelman and which parental copy is deleted in each?

15. Paternal deleted in PW, Maternal deleted in Angelman

79

MR, hyperphagia, obesity, hypogonadism, hypotonia

Prader-Willi

80

MR, seizures, ataxia, inappropriate laughter

Angelman

81

Hypophosphatemic rickets pathophys and genetics

X linked dominant. Increased phosphate wasting at proximal tubule

82

What characterizes mitochondrial myopathies on microscopy?

Ragged red fibers

83

Genetics and defect in achondroplasia

FGF receptor 3. AD. Associated with advanced paternal age

84

What gene is most commonly mutated in ADPKD and what chromosome is it on?

PKD1. Chromosome 16

85

Common complications of ADPKD

Polycystic liver disease, berry aneurysms (due to HTN), MVP

86

Genetics and defect (include chromosome if you know it) in FAP

APC gene (chr 5), AD

87

Genetics and defect in hyperlipidemia type IIA

LDL receptor defect, AD.

88

Genetics of Osler-Weber-Rendu

AD

89

Telangiectasia, recurrent epistaxis, skin discoloration, AVMs

Osler-Weber-Rendu (Hereditary hemorrhagic telangiectasia)

90

Genetics and defect in hereditary spherocytosis

AD defect in spectrin or ankyrin

91

Genetics and defect (include chromosome if you know it) in Huntingon. Also what are the NT levels like?

AD. Chromosome 4. Low levels of GABA and ACh

92

Genetics and main complications of Marfan

AD. Aortic incompetence and dissecting aortic aneurysms. Floppy mitral valve, subluxation of lenses

93

Genetics and defect (include chromosome if you know it) in MEN

AD. 2A and 2B associated with ret gene

94

Genetics and defect (include chromosome if you know it) in NF-1

AD. Chromosome 17

95

What disorder includes lisch nodules and what are they?

NF-1. Pigmented iris hamartomas

96

Genetics and defect (include chromosome if you know it) in NF-2

AD. Chromosome 22

97

What disorder includes bilateral acoustic schwannoma and juvenile cataracts?

NF-2

98

Genetics of tuberous sclerosis

AD

99

Facial lesions, hypopigmented spots, cortical and retinal hamartomas, seizures, MR, renal cysts and angiomyolipomas, cardiac rhabdomyomas, astrocytomas

Tuberous sclerosis

100

Genetics and defect (include chromosome if you know it) in VHL

VHL gene (a TS) on chromosome 3p

101

Hemangioblastomas on retina, cerebellum and medulla. RCC, constitutive expression of HIF and angiogenic growth factors

VHL

102

List AR disorders (10)

Albinism, ARPKD, CF, glycogen storage disorders, hemochromatosis, mucopolysaccharidoses (except Hunter), PKU, sickle cell, sphingolipidoses (except Fabry), thalassemias

103

Genetics and defect (include chromosome if you know it) in CF

CFTR gene (chr 7), AR

104

Common pulmonary infections in CF

Pseudomonas and S aureus

105

What type of channel is CFTR?

An ATP-Gated channel

106

Why do males with CF have infertility?

Bilateral absence of vas deferens

107

Treatment for CF

N-acetylcystein to loosen mucous plugs

108

List X recessive disorders (10)

Brutons, Wiskott-Aldrich, Fabrys, G6PD def, Ocular albinism, Lesch-Nyhan, Duchennes, Beckers, Hunters, Hemophilia A and B

109

What type of mutation occurs in duchennes?

X-linked frame-shift mutation (leads to deletion of dystrophin gene)

110

First muscles affected in duchennes

Hip muscles (hence Gowers sign)

111

Genetics and defect (include chromosome if you know it) in Fragile X

FMR1 gene is incorrectly methylated (X chr).

112

Macroorchidism, long face with large jaw, larage everted ears, autism, MVP, MR

Fragile X

113

What are the repeats in Fragile X, Friedreichs, Huntingtons, and Myotonic dystrophy respectively?

Fragile X - CGG, Friedreich - GAA, Huntington - CAG, Myotonic dystrophy - CTG

114

AFP levels in common in trisomies and NT defects

Trisomies 21 and 18 - low. Trisomy 13 - normal. NT defect - high

115

Trisomy 21 and 18 both have low AFP levels. What is the best way to differentiate them?

B-hCG. High in 21, Low in 18

116

In what instance would you see increased nuchal translucuency in utero

Trisomy 21

117

What is the in utero defect associated with high Inhibin A levels?

Trisomy 21

118

Flat facies, prominant epicanthal folds, simian crease, gap between 1st 2 toes, duodenal atresia, congenital heart diseaes

Downs syndrome

119

Most common complications of Downs syndrome

Duodenal atresia, septum primum, ASD, ALL, Alzheimers

120

What cause of Down syndrome has no maternal association?

Mosiacism. The other two causes are nondisjunction and robertsonian

121

Severe MR, rocker bottom feet, micrognathia (small jaw), low set ears, clenched hands, prominent occiput, congenital heart disease. Death within 1 year of birth

Edwards (trisomy 18)

122

Severe MR, rocker bottom feet, microphthalmia, microcephaly, cleft lip and palate, holoprosencephaly, polydactyly. Death within 1 year.

Pataus (trisomy 13)

123

Microcephaly, moderate to severe MR, epicanthal folds, VSD

Cri-du-chat (also high pitched cry, but that makes it too easy)

124

Deletion in cri du chat

Short arm of 5

125

Abnormal facies, MR, hypercalcemia, extreme friendliness, cardiovascular problems

Williams syndrome (microdeletion of chr 7 which includes elastin gene)

126

Defects in DiGeorge

CATCH-22. Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia

127

Fat soluble vitamins

ADEK

128

Water soluble vitamins (9)

B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), C (ascorbic acid), Biotin, Folate

129

What compound prevents squamous metaplasia?

Vitamin A

130

What can Vit A be used to treat (2)

AML (subtype M3) and Measles

131

Vit A deficiency

Night blindness, dry skin

132

Vit A excess

Arthralgias, fatigue, headaches, skin changes, sore throat, alopecia

133

Enzymes which require B1 (4)

Pyruvate dehydrogenase (glycolysis), Alpha-ketoglutarate dehydrogenase (TCA), Transketolase (HMP shunt, cytosolic), Branched-chain AA dehydrogenase

134

Classic triad of Wernicke-Korsakoff

Confusion, ophthalmoplegia, ataxia. Also shows up with confabulation, personality change, memory loss

135

Wernicke-Korsakoff results from damage to what structures?

Medial dorsal nucleus of thalamus and mammillary bodies

136

Dry beriberi

Polyneuritis, symmetrical muscle wasting

137

Wet beriberi

High output cardiac failure (dilated cardiomypoathy), edema

138

B2 deficiency

Cheilosis, corneal vascularization. NB - FAD (cofactor for succinate dehydrogenase) and FMN are derived from riboflavin

139

What is Vit B3 (niacin) used for and what can it be derived from?

Use in redox reactions (with NAD+ and NADP+), can be made from tryptophan

140

Vit B3 (niacin) deficiency

Pellagra - Diarrhea, Dermatitis, Dementia. Also glossitis

141

What can cause Vit B3 deficiency (3)

Hartnup disease (will also have pruritic rash, ataxia, loose stools), Malignant carcinoid, INH

142

Functions of Vit B5

Component of CoA and FA synthase

143

Vit B5 deficiency

Dermatitis, enteritis, alopecia, adrenal insufficiency

144

What compound can increase peripheral metabolism of levodopa?

Vitamin B6. NB - Vit B6 is required to make niacin (B3) from tryptophan

145

Functions of Vit B6

Transamination, decarboxylation, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, GABA

146

Vit B6 deficiency

Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia

147

What drugs can induce B6 deficiency?

INH and oral contraceptives

148

Macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms

Vit B12 deficiency

149

Methylmalonic acidemia is a defect in isomerization of what to what?

Methylmalonyl CoA to succinyl CoA (which requires B12)

150

What is the most common vitamin deficiency in the US?

Folic acid. Especially common in alcoholism and pregnancy

151

Why is IM Vit B12 given before a Shilling test?

To fill body stores of B12 so any absorbed B12 will end up in urine (where it can be measured)

152

Interpret the following Shilling test results (all numbers given are percentages): 1) D1 > 5, 2) D1 5

1 is normal. 2 is not pernicious anemia (may be fishworm, whipple, sprue, enteritis, etc). 3 is pernicious anemia

153

When we make methionine 3 compounds get converted to 3 other compounds. What are they?

Homocysteine to methionine. Methylcobalamin to cobalamin. 5-methyl THF to THF

154

Homocysteine can be used to make methionine. If we are deficient in B12 or Folate however, what other path does homocysteine go down?

Homocysteine to Cystathione to Cystine (requires B6)

155

What is the main methyl donor?

SAM

156

Biotin is a cofactor for what enzymes (3)

Pyruvate carboxylase, Acetyl-CoA carboxylase, Propionyl-CoA carboxylase

157

Symptoms and main causes of Biotin deficiency

Dermatitis, alopecia, enteritis. Antibiotic use or excessive ingestion of raw eggs.

158

What vitamin facilitates iron absorption?

Vit C

159

What is necessary for converting dopamine to NE?

Vitamin C

160

Swollen gums, bruising, hemarthrosis, anemia, poor wound healing

Scurvy (vit c deficiency)

161

Nausea, vomiting, diarrhea, fatigue, sleep problems, iron toxicity.

Vitamin C excess

162

What electrolyte abnormality usually leads to tetany?

Hypocalcemia

163

Two vitamins that are not in breast milk and should be supplemented

Vitamin D and Vitamin K

164

Hypercalcemia, hypercalciuria, loss of appetite, stupor. May be associated with sarcoidosis

Vitamin D excess

165

What is the main function of Vitamin E?

Protect RBCs and PMs from oxidation damage

166

Hemolytic anemia, muscle weakness, posterior column and spinocerebellar tract demyelination

Vitamin E def

167

Vitamin K dependent factors

2, 7, 9, 10, Proteins C and s

168

Delayed wound healing, hypogonadism, decrease in adult hair, dysgeusia, anosmia

Zinc deficiency (5)

169

Deficiency of what vitamin may predispose to alcoholic cirrhosis?

Zinc

170

Antidote for methanol or ethylene glycol poisoning

Fomepizole

171

Why do you get increased ketone and FA production in alcoholism?

Depletion of oxaloacetate (pyruvate diverted to lactate by low NAD+) shuts down TCA and diverts aCoA into ketones. Overproduction of malate increases NADPH and thus FA synthesis

172

What regenerates the NAD+ consumed in glycolysis from G3P --> 1,3BPG?

Pyruvate --> Lactate

173

Marasmus

Complete malnutrition leading to tissue and muscle wasting, loss of fat, variable edema (not nearly as much edema as kwashiorkor)

174

Give the rate limiting enzymes for the following: Glycolysis, Gluconeogenesis, TCA cycle, Glycogenolysis

PFK-1, F-1,6-Bisphosphatase, Isocitrate dehydrogenase, Glycogen phosphorylase

175

Give the rate limiting enzymes for the following: De novo pyrimidine synthesis, De novo purine synthesis, Urea cycle, FA synthesis, FA oxidation, Ketogenesis

Carbamoyl phosphate synthetase 2, Glutamine-PRPP amidotransferase, Carbamoyl phosphate synthetase 1, Acetyl-CoA carboxylase, Carnitine acyltransferase 1, HMG-CoA synthase

176

Acetyl-CoA is an allosteric activator of what pathway?

Gluconeogensis. This is because it stimulates pyruvate --> oxaloacetate. This can then go to PEP and eventually back up to glucose

177

What are the two main universal electron acceptors associated with vitamins and which vitamins is used to make each?

NAD+ (from Vit B3) and FAD+ (from Vit B2)

178

4 main uses of NADPH

1) Anabolic processes, 2) Respiratory burst, 3) P-450 system, 4) Glutathione reductase

179

What induces and inhibits hexokinase and glucokinase respectively?

Hexokinase - uninduced and inhibited by G-6-P. No induction. Glucokinase - Induced by insulin, no inhibition

180

What enzyme allows the liver to serve as a blood glucose buffer

Glucokinase. Also acts like a glucose sensor in B cells

181

In contrast to a previous card, something inhibits glucokinase. What is it?

Fructose-6-Phosphate

182

What things activate or inhibit the rate limiting step in glycolysis (PFK-1)?

Activate - AMP, Fructose-2,6-BP. Inhibit - ATP, Citrate

183

What things inhibit or activate pyruvate kinase (PEP to Pyruvate)?

Inhibit - ATP, Alanine, Activate - Fructose-1,6-BP

184

What things inhibit or activate pyruvate dehydrogenase (pyruvate to acetyl-CoA)

Inhibit - ATP, NADH, Acetyl-CoA. No activators

185

What enzyme allows us to make use of fructose if fructokinase is deficient?

Hexokinase (converts fructose to f-6-p, just like it does with glucose)

186

Which fructose related enzyme and its product are active in fed state? Which in fasting state? What protein regulates this process?

Fed state - PFK-2 makes more Fructose-2,6-Bisphosphate. Fasting state - Fructose Bisphosphatase 2 makes more Fructose-6-Phosphate. Protein Kinase A (resulting from insulin/glucagon) regulates this

187

Cofactors required for pyruvate dehydrogenase complex

Pyrophosphate (from B1, thiamine), FAD (from B2), NAD (from B3), CoA (from B5), Lipoic acid

188

What does arsenic inhibit and what are the findings in arsenic poisoning?

Lipoic acid (part of pyruvate and alpha-ketoglutarate dehydrogenase complexes). Findings are vomiting, rice water stools, garlic breath

189

Purely ketogenic amino acids

Lysine and Leucine

190

Which promotes glycolysis, high or low levels of Fructose-2,6-bisphosphate?

High levels

191

What are the four potential outcomes for a pyruvate molecule?

1) Alanine (carry AAs to liver), 2) Oxaloacetate (gluconeogenesis or TCA), 3) Acetyl-CoA (TCA), 4) Lactate (regenerate NAD+)

192

Deficiency of B1, B2, B3, B5 or Lipoic acid will stop what two steps related to the TCA?

Pyruvate dehydrogenase (pyruvate to acetyl-CoA) and a-KG dehydrogenase (a-KG to Succinyl CoA)

193

GTP generated in what step of the TCA can be used to regenerate PEP and start gluconeogenesis?

Succinyl-CoA to Succinate

194

Major ox phos poisons and the category of each

Cyanide and CO - electron transport inhibitors. Oligomycin - ATP synthase inhibitor. Aspirin and 2,4-DNP - Uncoupling agents

195

Where does gluconeogenesis occur (organs)?

Liver, kidney, intestinal epithelium

196

Irreversible enzymes required for gluconeogenesis (4)

Pyruvate carboxylase (biotin), PEP carboxykinase, Fructose-1,6-bisphosphatase, G-6-Phosphatase

197

Cholesterol synthesis requires what other biochemical pathway to be working?

HMP shunt

198

Sites where HMP shunt is active (organs)

Lactating mammary glands, liver, adrenal cortex, RBCs

199

Three differences between the nonoxidative and oxidative arms of the HMP shunt

1) The enzymes (G6PD for oxidative, transketolases for nonox), 2) B1 required for nonox (but ox is limiting), 3) Nonox is reversible, ox is irreversible

200

Chronic granulmatous disease is a deficiency of what enzyme?

NADPH oxidase

201

Two common examples of catalase-positive species which may cause serious infections in pts with chronic granulomatous disease

Staph aureus and Aspergillus

202

Defects and genetics of essential fructosuria and fructose intolerance. Which is more serious?

Essential frucosuria - fructokinase, AR. Fructose intolerance (more serious) - aldolase B, AR.

203

Hypoglycemia, jaundice, cirrhosis, vomiting

Fructose intolerance

204

Which tend to be more serious, fructose disorders or galactose disorders?

Galactose

205

Treatment for fructose intolerance (and reasoning)

Decreased intake of fructose and sucrose (which is glucose + fructose)

206

Defects and genetics of galactokinase deficiency and galactosemia. Which is more serious?

Galactokinase def - galactokinase, AR. Classic galactosemia (more serious) - Galactose-1-phosphate uridyltransferase, AR

207

Why are fructose disorders typically less serious than galactose disorders?

Fructose can still be converted to glucose-6-phosphate (through Fructose-6-Phosphate). Galactose has no exit but galactitol (which is toxic)

208

Infant with cataracts, failure to track objects or develop a social smile, few other symptoms

Galactokinase deficiency

209

Failure to thrive, jaundice, hepatomegaly, cataracts, MR

Classic galactosemia

210

Treatment for classic galactosemia and reasoning behind it

Exclude galactose and lactose (galactose + glucose)

211

What is the main toxic substance in galactose disorders and what does it damage primarily?

Galactitol causes cataracts

212

The more serious fructose and galactose deficiencies lead to depletion of what?

PO4 (because they are generating phosphate-sugars which cant be metabolized)

213

Give the two main steps in sorbitol metabolism

Glucose to Sorbitol (by Aldose reductase). Sorbitol to Fructose (by sorbitol dehydrogenase). NADPH required for rxn 1, NAD+ required for rxn 2

214

What cells are missing a sorbitol related enzyme, what enzyme is it, and what is the effect?

Schwann cells, lens, retina, and kidneys are missing sorbitol dehydrogenase. Sorbitol accumulates (and has osmotic effects). Cause of numerous problems in diabetics

215

What is another name for lactose and what enzyme metabolizes it to what?

Galactosyl-beta-1,4-glucose. Metabolized by lactase to galactose

216

Essential glucogenic amino acids

Met, Val, Arg, His

217

Essential glucogenic/ketogenic AAs

Ile, Phe, Thr, Trp

218

Which two AAs are required during periods of growth? Which two AAs are in high levels in histones?

Growth - Arg and His. Histones - Arg and Lys

219

What enzyme is the rate limiting step in the urea cycle and what substance activates this step?

Carbamoyl phosphate synthetase 1. Activated by N-acetylglutamate

220

Spastic paresis of lower extremity, choreoathetoid movements

Arginase deficiency. Will see increased arginine

221

What donates a NH4+ group into the urea cycle

Aspartate (which converts cirtulline to argininosuccinate)

222

AAs with 3 titrable protons

Histidine, arginine, lysine, aspartic acid, glutamic acid, cysteine, tyrosine

223

Treatments for hyperammonemia

Limit protein. Benzoate or phenylbutyrate (bind AAs leading to excretion). Lactulose to acidify Gi and trap NH4 for excretion

224

Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Ammonia intoxication

225

What is the most common urea cycle disorder and what is its genetics?

OTC deficiency. X recessive

226

OTC deficiency is X recessive. All the other urea cycle disorders are of what genetics?

AR

227

Enzyme deficiencies of the urea cycle (6)

1) Carbamoyl phosphate synthase, 2) OTC (most common), 3) Argininosuccinic acid synthase, 4) Argininosuccinic acid lyase, 5) Arginase, 6) N-acetylglutamate synthase (affects activator of rate limiting step rather than a step in the urea cycle per se)

228

Derivatives of phenylalanine (7)

Tyrosine (yields thyroxine) --> Dopa (yields melanin) --> Dopamine --> NE --> Epi

229

Derivatives of tryptophan

Niacin (requires B6, generates NAD+/NADP+) and Serotonin (requires BH4, generates melatonin)

230

Derivatives of arginine

Creatinine, urea, No

231

Breakdown products via MAO and COMT

Dopamine to HVA, NE to VMA, Epi to Metanephrine

232

Phenylethanolamine N-methyl transferase

NE to Epi (requires SAM). Activated by cortisol

233

What enzyme does carbidopa inhibit?

Dopa decarboxylase (converts dopa to dopamine with help of B6)

234

What vitamin is required to convert dopamine to NE and what enzyme carries this out?

Dopamine B-hydroxylase with Vitamin C

235

Defects and genetics of PKU

Deficiency of phenylalanine hydroxylase or BH4 (tetrahydrobiopterin) cofactor. AR

236

What becomes essential in PKU?

Tyrosine (which is made from Phe and subsequently makes Dopa, Dopamine, NE, and Epi)

237

MR, growth retardation, seizures, fair skin, eczema, musty body odor

PKU

238

When do you screen for PKU

2-3 days after birth

239

Microcephaly, MR, growth retardation, congenital heart defects

Maternal PKU

240

Defect and genetics of alkaptonuria (ochronosis)

Homogentistic acid oxidase deficiency. AR

241

Dark connective tissue, brown pigmented sclera, debilitating arthralgias (sometimes) but often asymptomatic.

Alkaptonuria. Urine will turn black on prolonged exposure to air

242

Defects and genetics of albinism

Tyrosinase defect (AR) or defective tyrosine transporters (variable inheritence). Can also result from lack of migration of neural crest cells

243

Defects and genetics of homocystinuria

AR. One of three defects: 1) Cystathionine synthase defect, 2) Decreased affinity of cystathionine synthase for pyridoxal phosphate (give B6), 3) Homocysteine methyltransferase def (give B12)

244

What becomes essential in homocystinuria?

Cysteine

245

Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis, renal infarcts

Homocystinuria (will also find high levels of homocysteine in urine)

246

Defect and genetics in cystinuria

AR. Defect in renal tubular transporter for cysteine, ornithine, lysine, and arginine (PCT)

247

Treatment for cystinuria

Acetazolamide to alkalinize urine

248

Defect in maple syrup urine disease

Blocked degradation of branched AAs (isoleucine, leucine, valine) due to decreased alpha-ketoacid dehydrogenase

249

What should you give in maple syrup disease and why?

Thiamine. Alpha-ketoacid dehydrogenase (which is deficient) requires B1, B2, B3, B5 and Lipoic Acid

250

Severe CNS defects, MR, death, strange smell to urine

Maple syrup disease

251

Defect and genetics of hartnup disease

AR. Defective neutral AA transporter on renal and intestinal epithelial cells. Will see tryptophan in urine

252

Hartnup disease leads to a condition very similar to what vitamin deficiency?

Pellagra (Vit B3 deficiency)

253

What is the effector for insulin, glucagon, and epi effects on glycogen metabolism in liver and muscle

cAMP --> PKA. PKA phosphorylates glycogen phosphorylase kinase, activating it

254

In glycogen, what is the bond at branches? What is the bond at linkages?

Branches - alpha 1,6. Linkages - alpha 1,4.

255

Severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly, increased uric acid

Von Gierkes disease (type 1). Deficiency of glucose-6-phosphatase

256

Cardiomegaly and early death

Pompes disease (type 2) infantile form. Deficiency of lysosomal alpha 1,4 glucosidase (acid maltase). Is the only glycogen storage disease that is also lysosomal

257

Diaphragm weakness, respiratory failure in an adult

Pompes disease adult form (type 2 glycogen storage). Deficiency of lysosomal alpha 1,4 glucosidase

258

What is the presentation of Cori disease and what is the enzyme deficiency?

Similar to Von Gierkes but with normal blood lactate (gluconeogenesis is intact). Debranching enzyme (alpha 1,6 glucosidase) deficiency

259

Painful muscle cramps, myoglobinuria with exercise

McArdles disease. Deficiency in skeletal muscle glycogen phosphorylase

260

Peripheral neuropathy of hands and feet, angiokeratomas, cardiovascular and renal disease

Fabrys disease. Deficiency of alpha galactosidase A

261

Defect and genetics of Fabrys disease

X recessive. Deficient alpha galactosidase A leads to accumulation of ceramide trihexosidase. Mainly affects fibroblasts

262

Hepatosplenomegaly, aseptic necrosis of femur, bone crises, abnormal looking macrophages

Gauchers disease. Most common lysosomal storage disease

263

Defect and genetics of Gauchers

Autosomal recessive. Deficiency of glucocerebrosidase leading to glucocerebroside accumulation

264

Progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells

Niemann-Pick

265

Defect and genetics of Niemann-Pick

Autosomal recessive. Sphingomyelinase deficiency

266

Progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, no hepatosplenomegaly

Tay-Sachs

267

Defect and genetics of Tay Sachs

AR. Defective hexosaminidase A leads to GM2 ganglioside accumulation

268

How do you differentiate Tay-Sachs from Niemann-Pick?

Hepatosplenomegaly in Niemann-Pick, none in Tay-Sachs

269

Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Krabbes disease

270

Defect and genetics in Krabbes disease

AR. Galactocerebrosidase deficiency

271

Central and peripheral demyelination with ataxia and dementia

Metachromatic leukodystrophy

272

Defect and genetics in metachromatic leukodystrophy

AR. Deficiency of arylsulfatase A leads to accumulation of cerebroside sulfate

273

Developmental delay, airway obstruction, corneal clouding, hepatosplenomegaly

Hurlers syndrome. Will also have gargoylism

274

Defect and genetics of Hurlers

AR. Alpha-L-iduronidase deficiency leads to accumulation of heparan sulfate and dermatan sulfate

275

Mild developmental delay, airway obstruction, hepatosplenomegaly, aggressive behavior

Hunters syndrome

276

Defect and genetics in Hunters

X recessive. Iduronate sulfatase leads to accumulation of heparan sulfate and dermatan sulfate (same substances that build up in Hurlers)

277

Weakness, hypotonia, hypoketotic hypoglycemia

Carnitine deficiency

278

High dicarboxylic acids, low glucose and ketones

Acyl-CoA dehydrogenase deficiency (cant breakdown FAs in mitochondria)

279

Glycerol from triglycerides is degraded to what by what and where (organ)?

To DHAP by Glycerol Kinase in the liver. DHAP can then undergo glycolysis or gluconeogenesis

280

What esterifies most plasma cholesterol?

LCAT

281

What degrades triglycerides in IDL and in adipocytes respectively?

IDL - Hepatic Lipase (HL). Adipocytes - Hormone-sensitive lipase. Otherwise TGs degraded by LPL (in chylomicrons and VLDL)

282

What transfers cholesterol esters to lipoprotein particles?

CETP

283

Give the major function of each of the following apolipoproteins: E, A-1, C-2, B-48, and B-100

E - mediates remnant uptake, A-1 activates LCAT, C-2 is a LPL cofactor, B-48 chylomicron secretion, B-100 binds LDL receptor (extrahepatic uptake)

284

Where is HDL secreted from?

Liver and intestine

285

Defect in type 1 familial dyslipidemia

Hyperchylomicronemia due to LPL deficiency or altered Apo C-2. Pancreatitis, hepatosplenomegaly, eruptive/pruritic xanthomas (no increased risk of atherosclerosis)

286

Defect in IIa familial hypercholesterolemia

Absent or reduced LDL receptors. AD. Accelereated atherosclerosis, tendon xanthomas, corneal arcus

287

Defect in type IV familial dyslipidemia

Hepatic overproduction of VLDL. Pancreatitis

288

Defect and genetics of abetalipoproteinemia

Failure to synthesize lipoproteins due to deficiencies in apoB-100 and apoB-48. AR

289

Failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness

Abetaliproteinemia

290

What acid base disorder do people with bulemia get and what is the major complication?

Metabolic alkalosis. High risk for arrhythmias with met alk

291

What is it called when you hear a crunch sound on lung auscultation, what causes it, and what condition often leads to it?

Hemimans crunch, usually secondary to Boerhaves syndrome (rupture esophagus due to wretching). Often associated with bulimia

292

If you can get them food, which child is more likely to die, one with kwashiorkor or one with marasmus?

The one with kwashiorkor. It has been wreaking havoc on their liver

293

Child with edema, flaky dermatitis, reddish hair, copper deficiency

Kwashiorkor

294

If a nonsmoker gets squamous metaplasia in the lung, what might have caused this?

Vitamin A deficiency

295

What should you associate with eating bear liver?

Hypervitaminosis A - cerebral edema, papilledema, headache

296

What two organs is hypervitaminosis A most toxic to?

Brain and liver

297

Where does PTH act to affect calcium reabsorption in the kidney?

The distal tubule (where thiazides act)

298

Where does PTH act to affect phosphorus reabsorption in the kidney?

It decreases phosphorus reabsorption in the proximal tubule. It also decreases bicarb reabsorption here too

299

What is the only hormone with a receptor on osteoclasts?

Calcitonin

300

What is released when Vitamin D and PTH respectively bind to osteoblasts?

Vitamin D - alk phos (associated with bone growth), PTH - IL-1 (osteoclast activating factor)

301

Why would a patient on phenytoin get hypocalcemia?

CYP450 system metabolizes Vitamin D. Phenytoin induces this system

302

What enzyme is increased by drugs that induce the CYP450 system?

GGT

303

Two things you see in kids with rickets that you dont see in adults with osteomalacia

Soft skulls and Ricketic rosaries (bumps around ribs)

304

Most common complication of hypervitaminosis D

Kidney stones

305

What vitamin deficiency is associated with hemolytic anemia?

Vitamin E

306

What is the most significant complication of hypervitaminosis E and why?

Anticoagulation. Inhibits synthesis of Vitamin K dependent factors. Be especially careful if the patient is on warfarin as these will have synergistic effects

307

Why are newborns usually deficient in vitamin K?

They have about a 3 day supply from mom. Otherwise, we get most Vitamin K from bacteria in our gut, and they havent been colonized yet

308

Main window for hemorrhagic disease of the newborn

Days 3 to 5 (maternal supplies last until day 3, and bacteria colonize by day 5)

309

What converts Vitamin K to the active form?

Epoxide reductase (usually in bacteria)

310

What does vitamin K do to vitamin K dependent clotting factors and how does that allow them to work?

Gamma carboxylates their glutamic acid residues. This allows them to bind Ca which they use to bind to clots

311

Most common causes of vitamin K deficiency

Antibiotics, being a newborn, malabsorption, warfarin

312

Hemorrhage around hair follicules, cork screw hair, glossitis, kelosis around ankles, hemorrhagic diathesis

Scurvey

313

Most common complication of hypervitaminosis C

Renal stones (uric acid, others as well)

314

Most common palsies seen in dry beriberi

Common peroneal (foot drop), Radial (wrist drop), Ulnar (claw hand)

315

What should you give a patient before you give them glucose?

Thiamine (to prevent wernickes)

316

What condition often presents with a necklace configuration dermatitis?

Pellagra (along with dementia and diarrhea)

317

Which vitamin is needed for heme synthesis and what is its role?

B6, it is a cofactor for the first reaction (ALA synthase)

318

How are AST and ALT relevant to starvation?

Transamination (they are transaminases) are needed to convert AAs (for example from muscle) such as alanine to substrates that can be used for gluconeogenesis

319

What two AAs can be transaminated to make substrates for gluconeogenesis and what substrates do they make respectively?

Alanine can be made into pyruvate, Aspartate can be made into oxaloacetate

320

Most common cause of B6 deficiency

INH

321

Is Biotin more related to glycolysis or gluconeogenesis

Gluconeogenesis. It is a cofactor for pyruvate decarboxylase (which turns pyruvate to OAA, allowing the option of gluconeogenesis)

322

Alopecia with a rash in a patient consuming lots of raw eggs

Biotin deficiency

323

What does chromium do in the body?

Helps insulin do its job

324

What does copper do in the body?

Plays a role in lysl oxidase (crossbridging of collagen fibrils and elastic tissue). Deficiency leads to red hair and dissecting aortic aneurysm

325

What role does selenium play in the body?

Cofactor in HMP shunt (glutathione peroxidase reaction)

326

What is the relationship between zinc and wound healing?

Zinc necessary for collagenase (breaks down Type 3 so it can be replaced with Type 1)