Biochemistry Flashcards
1
Q
Which histone is not in the nucleosome core?
A
H1
2
Q
Which makes DNA active and which makes it less: methylation and acetylation?
A
More active - acetylation, less active - methylation
3
Q
Which bases are purines and which are pyrimidines?
A
Purines - AG, Pyrimidines - CUT
4
Q
AAs required for purine synthesis
A
Glycine, Aspartate, Glutamine
5
Q
AAs required for pyrimidine synthesis
A
Aspartate
6
Q
Main branch point for both pyrimidine and purine synthesis
A
PRPP
7
Q
What pathways is carbamoyl phosphate involved in?
A
De novo pyrimidine synthesis and the urea cycle
8
Q
OTC deficiency
A
OTC involved in urea cycle. Leads to increase in carbamoyl phosphate which is converted to orotic acid (pyr and pur synthesis)
9
Q
What does hydroxyurea inhibit?
A
Ribonucleotide reductase
10
Q
Does each of the following inhibit purine or pyrimidine synthesis? 6-MP, 5-FU, MTX, Trimethoprim
A
6-MP is purine, the others are all pyrimidine
11
Q
Defects that cause orotic aciduria (2) and the genetics
A
Orotic acid phosphoribosyltransferase or orotidine 5-phosphate decarboxylase. AR
12
Q
How do we distinguish between orotic aciduria and OTC deficiency?
A
OTC deficiency includes signs of hyperammonemia (due to backflow into urea cycle). No hyperammonemia in orotic aciduria
13
Q
Treatment for orotic aciduria
A
Uridine (inhibits carbamoyl phosphate synthase II)
14
Q
ADA deficiency causes feedback inhibition of what enzyme?
A
Ribonucleotide reductase
15
Q
What will be present in high levels in the blood and what enzyme will be hyperactive in Lesch-Nyhan?
A
Uric acid present in high levels (failure to salvage). PRPP will be hyperactive (must make all new purines)
16
Q
Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
A
Lesch-Nyhan
17
Q
Genetics of Lesch-Nyhan
A
X recessive
18
Q
Prokaryotic DNA polymerases and their functions
A
DNA pol 3 - synthesizes 5 to 3, proofreads 3 to 5. DNA pol 1 - removes RNA primers 5 to 3.
19
Q
Defect in xeroderma pigmentosum
A
Excision of thymine dimers (failure of nucleotide excision repair)
20
Q
Give the actors in base excision repair in order
A
1) Glycosylase, 2) Endonuclease and lyase, 3) DNA pol, 4) Ligase
21
Q
Defect in HNPCC
A
Failure of mismatch repair
22
Q
Defect in ataxia telangiectasia
A
Failure of nonhomologous end joining (a type of DNA repair)
23
Q
What direction is mRNA read? What direction does protein synthesis occur in?
A
mRNA read 5 to 3. Protein synthesis is N to C
24
Q
mRNA stop codons and what are they recognized by?
A
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
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Derivatives of tryptophan
Niacin (requires B6, generates NAD+/NADP+) and Serotonin (requires BH4, generates melatonin)
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Derivatives of arginine
Creatinine, urea, No
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Breakdown products via MAO and COMT
Dopamine to HVA, NE to VMA, Epi to Metanephrine
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Phenylethanolamine N-methyl transferase
NE to Epi (requires SAM). Activated by cortisol
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What enzyme does carbidopa inhibit?
Dopa decarboxylase (converts dopa to dopamine with help of B6)
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What vitamin is required to convert dopamine to NE and what enzyme carries this out?
Dopamine B-hydroxylase with Vitamin C
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Defects and genetics of PKU
Deficiency of phenylalanine hydroxylase or BH4 (tetrahydrobiopterin) cofactor. AR
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What becomes essential in PKU?
Tyrosine (which is made from Phe and subsequently makes Dopa, Dopamine, NE, and Epi)
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MR, growth retardation, seizures, fair skin, eczema, musty body odor
PKU
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When do you screen for PKU
2-3 days after birth
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Microcephaly, MR, growth retardation, congenital heart defects
Maternal PKU
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Defect and genetics of alkaptonuria (ochronosis)
Homogentistic acid oxidase deficiency. AR
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Dark connective tissue, brown pigmented sclera, debilitating arthralgias (sometimes) but often asymptomatic.
Alkaptonuria. Urine will turn black on prolonged exposure to air
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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
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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
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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)
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Treatment for cystinuria
Acetazolamide to alkalinize urine
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Defect in maple syrup urine disease
Blocked degradation of branched AAs (isoleucine, leucine, valine) due to decreased alpha-ketoacid dehydrogenase
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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
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Severe CNS defects, MR, death, strange smell to urine
Maple syrup disease
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Defect and genetics of hartnup disease
AR. Defective neutral AA transporter on renal and intestinal epithelial cells. Will see tryptophan in urine
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Hartnup disease leads to a condition very similar to what vitamin deficiency?
Pellagra (Vit B3 deficiency)
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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
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In glycogen, what is the bond at branches? What is the bond at linkages?
Branches - alpha 1,6. Linkages - alpha 1,4.
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Severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly, increased uric acid
Von Gierkes disease (type 1). Deficiency of glucose-6-phosphatase
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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
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Diaphragm weakness, respiratory failure in an adult
Pompes disease adult form (type 2 glycogen storage). Deficiency of lysosomal alpha 1,4 glucosidase
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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
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Painful muscle cramps, myoglobinuria with exercise
McArdles disease. Deficiency in skeletal muscle glycogen phosphorylase
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Peripheral neuropathy of hands and feet, angiokeratomas, cardiovascular and renal disease
Fabrys disease. Deficiency of alpha galactosidase A
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Defect and genetics of Fabrys disease
X recessive. Deficient alpha galactosidase A leads to accumulation of ceramide trihexosidase. Mainly affects fibroblasts
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Hepatosplenomegaly, aseptic necrosis of femur, bone crises, abnormal looking macrophages
Gauchers disease. Most common lysosomal storage disease
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Defect and genetics of Gauchers
Autosomal recessive. Deficiency of glucocerebrosidase leading to glucocerebroside accumulation
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Progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells
Niemann-Pick
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Defect and genetics of Niemann-Pick
Autosomal recessive. Sphingomyelinase deficiency
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Progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, no hepatosplenomegaly
Tay-Sachs
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Defect and genetics of Tay Sachs
AR. Defective hexosaminidase A leads to GM2 ganglioside accumulation
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How do you differentiate Tay-Sachs from Niemann-Pick?
Hepatosplenomegaly in Niemann-Pick, none in Tay-Sachs
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Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Krabbes disease
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Defect and genetics in Krabbes disease
AR. Galactocerebrosidase deficiency
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Central and peripheral demyelination with ataxia and dementia
Metachromatic leukodystrophy
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Defect and genetics in metachromatic leukodystrophy
AR. Deficiency of arylsulfatase A leads to accumulation of cerebroside sulfate
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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
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Mild developmental delay, airway obstruction, hepatosplenomegaly, aggressive behavior
Hunters syndrome
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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)
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Weakness, hypotonia, hypoketotic hypoglycemia
Carnitine deficiency
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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
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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)
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What transfers cholesterol esters to lipoprotein particles?
CETP
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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)
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Where is HDL secreted from?
Liver and intestine
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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)
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Defect in IIa familial hypercholesterolemia
Absent or reduced LDL receptors. AD. Accelereated atherosclerosis, tendon xanthomas, corneal arcus
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Defect in type IV familial dyslipidemia
Hepatic overproduction of VLDL. Pancreatitis
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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
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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
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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
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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)
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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
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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
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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)
