Biochemistry Flashcards
(284 cards)
1
Q
What is the only histone that is not located in the nucleosome core?
A
H1
2
Q
what is the form of chromatin that is transcriptionally active?
A
Euchromatin
3
Q
What are the purine nucleotides?
What are the pyrimidine nucleotides?
A
Purines - A, G
Pyrimidines - C, U, T
4
Q
How can you make uracil from cytosine?
A
Deamination of cytosine makes uracil
5
Q
What are the amino aids necessary fro purine synthesis?
A
GAG
Glycine
Aspartate
Glutamine
you also need tetrahydrofolate
6
Q
what is the rate limiting enzyme in pyrimidine base production?
A
Carbamoyl phosphate synthetase II
7
Q
What enzyme does Hydroxyurea block that’s used in the synthesis of pyrimidines?
A
Hydroxyurea blocks ribonucleotide reductase
Used to treat sickle cell disease and cancer
8
Q
What enzyme does 5-FU block that’s used in the synthesis of pyrimidines?
A
Thymidylate synthase is blocked therefore you can’t make dTMP
9
Q
What enzyme does MTX/TMP block that’s used in the synthesis of pyrimidines?
A
Dihydrofolate reductase is blocked therefore you can’t make dTMP
10
Q
What enzyme does 6-MP block that’s used in the synthesis of purines?
A
6-MP inhibits glutamine PRPP Amidotransferase
Note that this is the rate limiting enzyme in purine synthesis
11
Q
What enzyme does Mycophenolate block that’s used in the synthesis of purines?
A
Mycophenolate blocks IMP dehydrogenase so you can’t make GMP
12
Q
Autosomal recessive disease where you are unable to convert orotic acid to UMP because of defect in UMP synthase
A
Orotic aciduria
effects de novo pyrimidine synthesis pathway
13
Q
Patient presents with megaloblastic anemia that does NOT improve with administration of vitamin B12 or folic acid, failure to thrive and they do NOT have hyperammonemia. The patient has increased orotic acid in the urine
A
Orotic aciduria
14
Q
What is the treatment for orotic aciduria
A
Oral uridine administration
15
Q
What two drugs inhibit xanthine oxidase?
A
Allopurinol and Febuxostat
16
Q
What immunosuppressants do you need to decrease when you are also giving a patient allopurinol or febuxostat?
A
Azathioprine and 6-MP
17
Q
What is the triad seen in SCID?
A
- severe recurrent infections
- chronic diarrhea
- failure to thrive
18
Q
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase therefore preventing DNA synthesis and therefore decreasing lymphocyte count
A
Adenosine deaminase deficiency
leads to SCID, AR disease
19
Q
Patient presents with excess uric acid production and de novo purine synthesis. They have a defective purine salvage pathway because they do not have HGPRT
A
Lesch nyhan syndrome
HGPRT converts hypoxanthing to IMP
20
Q
A patient is found with retardation, self-mutilation, aggression, hyperuricemia, gout, and choreoathetosis
A
Lesch-Nyhan syndrome
21
Q
What can you use to treat lesch-nyhan syndrome?
A
Allopurinol, but note that this will not help with CNS problems
22
Q
a point mutation in DNA where it results in the same amino acid, often the third base has changed (tRNA wobble)
A
Silent mutation
23
Q
A point mutation where there has been a change in the amino acid but it’s conservative because the new amino acid is similar in chemical structure but the result is a polypeptide product that has different structural or functional properties
A
missense mutation
Ex - sickle cell
24
Q
A point mutation that results in an early stop codon
A
Nonsense mutation
25
A point mutation that results in misreading of all nucleotides downstream, often resulting in a truncated, nonfunctional protein
Frameshift mutation
26
What autoantibody is made against topoisomerase?
anti-Scl-70
| seen in diffuse scleroderma
27
mutation in nucleotide excision repaid resulting in lack of repair of pyrimidine dimers due to UV light exposure
------------children of the night
Xeroderma Pigmentosum (AR)
28
what is the repair mechanism where newly synthesized strand is recognized and mismatched nucleotides (like a T with a G) are removed and gap is filled and resealed?
Mismatch Repair
29
In what cancer is mismatch repair mutated?
hereditary nonpolyposis colorectal cancer
30
a patient presents with decreased IgA, cerebellar ataxia, poor smooth pursuit of the eyes and they are sensitive to ionizing radiation. the patient has a mutated nonhomologous end joining
Ataxia telangiectasia
31
What is the mRNA start codon?
AUG
methionine in eukaryotes
formylmethionine (f-met) in prokaryotes
32
What are the 3 mRNA stop codons?
UGA
UAA
UAG
33
how many RNA polymerases do prokaryotes have and what do they do?
Prokaryotes have 1 RNA polymerase that makes rRNA, mRNA and tRNA
34
What antibiotic inhibits prokaryote RNA polymerase?
Rifampin
35
What are the RNA polymerases used in eukaryotes and what do they make?
RNA polymerase 1 - makes rRNA
2- makes mRNA
3- makes tRNA
36
a patient eats a amanita phalloides death cap mushroom and gets severe hepatotoxicity. What is the toxin and what is it inhibiting?
Alpha amanitin is the toxin and it inhibits RNA polymerase II
37
Where does RNA processing occur and what are the 3 stages of RNA processing?
Occurs in the nucleus
1. capping on 5' end (addition of 7-methylguanosine cap via SAM)
2. polyadenylation on 3' end, signal is AAuAAA
3. splicing out introns
38
what sequence sits at the 3' end of tRNA?
CCA
39
what antibiotic binds to the 30S subunit preventing attachment of aminoacyl-tRNA from entering the acceptor site?
Tetracyclines
40
what enzyme is responsible for adding an amino acid to the tRNA?
aminoacyl-tRNA synthetase
41
What antibiotics bind to 30S and inhibit formation of initiation complex and causes misreading of mRNA
Aminoglycosides
42
What antibiotics binds the 50s subunit and inhibits peptidyl transferase? (23s rRNA)
Chloramphenicol
43
what antibiotics bind to the 50s subunit and prevent release of uncharged tRNA after it has donated its amino acid, thereby preventing the translocation step?
Macrolides
44
what tumor suppressors prevent the G1 to S phase progression?
Rb and p53
45
What are the Cyclin/CDK involved in G1 to S phase?
Cyclin D with CDK4 and Cyclin E with CDK2
46
What are the cyclin/CDK involved in the G2 to M phase?
Cyclin A with CDK2 and Cyclin B with CDK1
47
what are the functions of smooth ER?
1. steroid synthesis
| 2. detoxification of drugs and poisons
48
What is responsible for synthesizing enzymes like ChAT and peptide neurotransmitters in neurons?
Nissl bodies or RER found only in dendrites
49
What must be added to a protein in order for it to go to the lysosome?
Mannose-6-phosphate
50
A patient is deficient in a phosphotransferase and is unable to add mannose-6-phosphate to proteins. what is the disease and what's the result?
The patient has I cell disease
| This results in enzymes being secreted outside the cell instead of being targeted to the lysosome
51
A patient presents with coarse facial features, clouded corneas, restricted joint movement and high plasma levels of lysosomal enzymes. what is this?
I cell disease
often fatal in childhood
52
Name 5 drugs that act on microtubules
1. Mebendazole
2. Griseofulvin
3. Vincristine/Vinblastine
4. Paclitaxel
5. Colchicine
53
What are the two molecular motor proteins that transport cellular cargo toward opposite ends of microtubule tracts?
Dynein - retrograde to microtubule (+ --> -)
| Kinesin - anterograde to microtubule (- --> +)
54
a patient presents with recurrent pyrogenic infections, partial albinism, and peripheral neuropathy. What is the syndrome and what is mutated?
Chediak higashi syndrome
Mutated lysosomal trafficking regulator gene (LYST)
55
A patient presents with decreased fertility, bronchiectasis, and recurrent sinusitis what is the syndrome and what is the defect?
The patient has Kartagener's syndrome (primary ciliary dyskinesia)
They have immotile cilia due to a dynein arm defect - associated with situs inversus
56
What cell type is seen with a vimentin stain?
Connective tissue
Sarcomas
57
What cell type is seen with a desmin stain?
Muscle
rhabdo or leiomyoscaroma
58
What cell type is seen with a cytokeratin stain
Epithelial cells
Carcinoma
59
What cell type is seen with a GFAP stain?
Neurogluia
Astrocytoma, glioblastoma
60
What cell type is seen with a neurofilament stain?
Neurons
Neuroblastoma, primitive neuroectodermal tumor
61
what drug inhibits the Na/K ATPase pump by binding to the K+ site?
Ouabain
62
What is the mnemonic to remember collagen types 1 - 4?
Strong (1), Slippery (2), Bloody (3), Bowel Movement (4)
63
Where is type 1 collagen found
bone, skin, tendon, dentin, fascia, cornea, late wound repair
64
Where is type 2 collagen found
Cartilage (including hyaline), vitreous body, nucleus pulposus
65
where is type 3 collagen found
Reticulin - skin, blood vessels, uterus, fetal tissue, granulation tissue
66
where is type 4 collagen found
Basement membrane or basal lamina
67
A patient is deficient in vitamin C and they are DX with scurvy, what exactly can they not do?
the step of collagen synthesis with hydroxylation of specific proline and lysine residues
68
if a patient can't form a triple helix during the glycosylation step of collagen synthesis, what disorder do they most likely have?
Osteogenesis imperfecta
69
If a patient is unable to perform the cross linking step in collagen synthesis to make collagen fibrils, what disorder do they most likely have?
Ehlers danlos
70
A patient presents with multiple fractures with minimal trauma, blue sclerae (transluscent CT over the choroidal veins), hearing loss and dental imperfections (lack of dentin). What is the name of the disorder and the defect
Osteogenesis imperfecta. Defect in type 1 collagen. the most common form is AD and is due to decreased production of otherwise normal type 1 collagen
71
A patient presents with hyperextensible skin, tendency to bleed and hypermobile joints
Type 1 or 5 collagen most frequently
Ehlers danlos
72
A patient presents with hematuria, oliguria, high frequency hearing loss - what's wrong with him?
Alport syndrome
Defect in Type 4 collagen - basement membranes
73
a patient presents with hyperelastic joints, problems wit heart vales, aorta, very tall, arachnodactyly, pectus carinatum and Steinberg sign. What is the syndrome and defect?
Marfan syndrome - fibrillin defect
74
Why do we get wrinkly?
reduced collagen and elastin production
75
What is the blotting procedure where you use a known DNA probe to ID a DNA sample?
Southern blotting
76
What is the blotting procedure where you use a known DNA probe with an RNA sample. This is useful for studying mRNA levels
Northern blot
77
What is the blotting procedure where you use an Ab probe to look at a protein sample
Western blot
78
What is the blotting procedure where you use a labeled oligonucleotide probe to look at DNA binding proteins like transcription factors
Southwestern blot
79
What type of ELISA uses a test antigen to see if a specific antibody is present in a person's blood?
Indirect ELISA
80
What type of ELISA uses a test antibody to see if a specific antigen is in a patients blood?
Direct ELISA
81
What technique should you use is you want to look for specific localization of genes and direct visualization of anomalies at the molecular level?
FISH
82
What is the genetic term where the phenotype varies among individuals with the same genotype. Example: 2 patients with neurofibromatosis type 1 may have varying disease severity.
Variable expressivity
83
What is the genetic term where not all individuals with a mutant genotype shows the mutant phenotype. Example: may skip a generation, BRCA1 gene mutation doesn't always result in breast or ovarian cancer?
Incomplete penetrance
84
what is the genetic term where one gene contributes to multiple phenotypic effects? Example: PKU causes many seeminly unrelated symptoms ranging from mental retardation to hair/skin changes
Pleiotropy
85
What is the genetic term where differences in gene expression depend on whether the allele is of maternal or paternal origin
Imprinting
86
What is the genetic term where there is increased severity or earlier onset of disease in succeeding generations?
Anticipation
87
What is the genetic term where if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. This is NOT true of oncogenes.
Loss of heterozygosity
"two hit hypothesis"
88
What is the genetic term that exerts a dominant effect where a heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning. Example: mutation of a transcription factor in its allosteric site. Nonfunctioning mutant can still bind DNA, preventing wild type transcription factor from binding.
Dominant negative mutation
89
What is the genetic term where there's a tendency for certain alleles at 2 linked loci to occur together more often than expected by chance. Measured in a population, not in a family, and often varies in different populations?
Linkage disequilibrium
90
What is the genetic term that occurs when cells in the body differ in genetic makeup due to postfertilization loss or change of genetic information during mitosis.
Mosaicism
91
What is the genetic term where mutations at different loci can produce the same phenotype? Examples include how mafran's syndrome, MEN 2B, and homocystinuria all cause marfanoid habitus. or all the different things that can cause albinism
Locus heterogeneity
92
What is the genetic term where there's the presence of both normal and mutated mitochondrial DNA, resulting in variable expression in mitochondrial inherited disease?
Heteroplasmy
93
A patient presents with mental retardation, hyperphagia, obesity, hypogonadism and hypotonia. They also have a chromosome 15 problem where the mom gene is inactivated and the dad gene is deleted.
Prader-willi syndrome
94
A patient presents with mental retardation, seizures, ataxia, and inappropriate laugher. They also have a chromosome 15 problem where the dad gene is inactivated and the mom gene is deleted
Angelman's syndrome
95
A patient presents with dwarfism, short limbs, larger head, but trunk size is normal. They have a super old dad. Whats the disorder, the inheritance pattern and the defect?
Achondroplasia, AD, defect of fibroblast growth factor receptor 3
96
a patient presents with a colon covered with adenomatous polyps after puberty. What is the disease, inheritance pattern and the defect?
Familial adenomatous polyposis. This is due to a mutation on chromosome 5, APC gene
The concern is that it progresses to colon cancer unless colon is resected
97
a patient presents with bilateral massive enlarged kidneys. They have flank pain, hematuria, hypertension, and progressive renal failure. What is the disease, inheritance pattern and the defect?
Autosomal dominant polycystic kidney disease
| The defect is on chromosome 16, PKD1 gene
98
A patient presents with elevated LDL due to defective or absent LDL receptor. They have severe atherosclerotic disease early in life, tendon xanthomas and they may have an MI very early in life. What is the disease, inheritance pattern and the defect?
```
Familial hypercholesterolemia (Hyperlipidemia type IIA)
Autosomal dominant
```
99
A patient presents with telangiectasia, recurrent epistaxis, skin discolorations and arteriovenous malformations. What is the disease, inheritance pattern and the defect?
This is Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - AD
This is a inherited disorder of blood vessels
100
A patient presents with hemolytic anemia, increased MCHC, increased viscosity in blood, jaundice, worsened with viral infections and abnormal osmotic fragility test. What is the disease, inheritance pattern and the defect?
Hereditary spherocytosis. AD. This is spheroid erythrocytes due to a spectrin or ankyrin defect.
101
A patient presents with depression, progressive dementia, choreiform movements, caudate atrophy, and decreased levels of GABA and ACh in the brain. What is the disease, inheritance pattern and the defect?
This is Huntington's disease (AD), gene located on chromosome 4 it is a trinucleotide repeat (CAG)
102
A patient presents with café-au-lait spots, neural tumors, lisch nodules (pigmented iris hamartomas), scoliosis and optic pathway gliomas. What is the disease, inheritance pattern and the defect?
This is neurofibromatosis type 1 (von Recklinghausen's disease) AD. defect on long arm of chromosome 17
103
A patient presents with tinnitus, balance problems, hearing loss due to bilateral acoustic schwannoma and juvenile cataracts. What is the disease, inheritance pattern and the defect?
This is neurofibromatosis type 2. AD
| NF2 gene on chromosome 22
104
A patient presents with seizures, intellectual disability, and angiofibromas. they also have ash leaf spots on skin, renal cysts and renal angiomyolipomas. What is the disease, inheritance pattern and the defect?
Tuberous sclerosis - AD, mutated hamartin (tuberin) gene
shwos incomplete penetrance and variable persentation
105
A patient presents with hemangioblastomas or retina/cerebellum/medulla, the majority of affected individuals also develop multiple bilateral renal cell carcinomas and other tumors. What is the disease, inheritance pattern and the defect?
This is von Hippel-Lindau disease, AD. deletion of VHL gene (tumor suppressor) on chromosome 3.
results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
106
what deletion is seen in cystic fibrosis?
CFTR gene is deleted on chromosome 7, commonly a deletion of Phe 508
this is AR
107
A patient presents with recurrent pulmonary infections, chronic bronchitis, bronchiectasis, pancreatic insufficiency, nasal polyps and meconium ileus as a newborn. What is wrong with them?
Cystic fibrosis
108
What is the inheritance and the mutation seen in Duchenne's muscular dystrophy?
X-linked frameshift mutation, deletion of dystrophin gene
onset before age 5 yo
109
How do you diagnose muscular dystrophies?
Muscle biopsy and increased CPK
as the disease progresses the CPK will decreased due to inactivity and muscle loss
110
what is the less severe form of duchennes muscular dystrophy?
Becker's
| This is a X-linked mutated dystrophin gene
111
A patient presents with marcoorchidism, long face with a large jaw, large everted ears, autism, mitral valve prolapse and mental retardation.
Fragile X syndrome
X linked. CGG repeat - FMR1 gene
112
What is the trinucleotide repeat seen in Friedreich's ataxia?
GAA
113
What is the trinucleotide repeat seen in myotonic dystrophy?
CTG - autosomal dominant
114
what 2 problems do you worry about with kids with Down's syndrome?
increased risk of ALL and increased risk of Alzheimer's disease
115
A patient is pregnant and their quad screen shows decreased AFP, increased beta hCG, decreased estriol and increased inhibin A, what are you worried about?
Down syndrome
116
A 1 year old presents with severe MR, rocker bottom feet, micrognathia (small jaw), low set ears, clenched hands, prominent occiput and congenital heart defects.
Edwards syndrome
Trisomy 18
117
A patient is pregnant and their quad screen shows decreased AFP, decreased beta-hCG, decreased estriol and normal inhibin A, what are you worried about?
Edwards syndrome
118
A patient presents with severe MR, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly and congenital heart disease. what do they have?
Patau's syndrome - trisomy 13
119
what is it called when the long arms of two acrocentric chromosomes fuse at the centromere and the 2 short arms are lost?
Robertsonian translocation
120
A patient has cri-du-chat syndrome - where is the deletion?
microdeletion of short arm of chromosome 5
121
a patient has Williams syndrome - where is the deletion?
microdeletion of long arm of chromosome 7
122
A patient presents with elf-like facies, intellectual disability, hypercalcemia, well developed verbal skills, extreme friendliness with strangers and cardiovascular problems. what is the syndrome and why do they have hypercalcemia?
Williams syndrome
They have hypercalcemia due t increased sensitivity to vitamin D
123
90% of DiGeorge patients have what deletion?
Chromosome 22 q 11 deletion
124
A patient presents with arthralgias, fatigue, headaches, skin changes, sore throat and alopecia. what vitamin are they overloaded with?
Vitamin A - retinol
125
a patient presents with confusion, ophthalmoplegia, ataxia and confabulation, personality changes, memory loss that's permanent. They are a raging alcoholic. what's the vitamin Deficiency and what is damaged?
Thiamine deficiency leading to Wernicke-Korsakoff syndrome
Damage is to the medial dorsal nucleus of the thalamus and mammillary bodies.
126
What should you always give to an alcoholic or malnourished patient before you give them glucose?
Thiamine should always be given before you give glucose
127
A patient presents with diarrhea, dermatitis and dementia - what vitamin are they deficient in?
Niacin or Vit B3 leading to Pellagra
note patients can also have glossitis
128
A patient presents with convulsions, hyperirritability and peripheral neuropathy. The patient also has sideroblastic anemia what drugs did they take too much of?
Oral contraceptives and INH can lead to a deficiency of Vitamin B6 (pyridoxine)
129
What should a patient on INH be supplemented with?
Vitamin B 3 (niacin) and vitamin B6 (pyridoxine)
130
A patient presents with macrocytic megaloblastic anemia without neurological symptoms, what is the diagnosis?
Folic acid (vitamin B9) deficiency
131
where is vitamin B 12 absorbed in the gut?
terminal ileum
132
If a patient has increased methylmalonic acid and increased homocystene, what is the patient deficient in?
Vitamin B 12
133
If a patient has increased homocysteine but normal MMA levels, what is the patient deficient in?
Folic acid (Vitamin B 9)
134
What vitamin helps with iron absorption by keeping iron in the Fe2+ reduced state?
Vitamin C (ascorbic acid)
135
what enzyme from the kidney converts vitamin D from its stored form to its active form?
1 alpha hydroxylase
136
what is breast milk decreased in that you should supplement in dark-skinned patients?
Breast milk has decreased vitamin D
137
in what disease do you see EXCESS vitamin D, and why?
Sarcoidosis, due to increased activation of vitamin D by epithelioid macrophages
138
A patient presents with increased fragility of RBCS (hemolytic anemia), muscle weakness, posterior column and spinocerebellar tract demyelination leading to ataxia and peripheral neuropathy. what vitamin are they deficient in?
Vitamin E
139
how does vitamin K activates factors 2, 7, 9, 10, protein C and protein S?
Catalyzes gamma-carboxylation of glutamic acid residues on various proteins
140
what vitamin are neonates given at birth to prevent hemorrhage?
Vitamin K
neonates have a sterile gut and therefore they do not have the ability to make vitamin K
the patient would have increased PT and aPTT but normal bleeding time
141
a patient presents with delayed wound healing, hypogonadism, decreased adult hair (axilla, facial, pubic), dysgeusia, and anosmia. What vitamin might they be deficient in?
Zinc deficiency
142
what are two enzymes that require zinc?
Lactate dehydrogenase and carbonic anhydrase
143
Give the metabolism of ethanol.... ready... go
Ethanol to Acetaldehyde via alcohol dehydrogenase
| acetaldehyde to acetate via acetaldehyde dehydrogenase
144
What are the limiting reagents in ethanol metabolism?
NAD+ (gets converted to NADH at each step)
145
What enzyme does Fomepizole block?
Fomepizole blocks alcohol dehydrogenase
can be used to treat methanol or ethylene glycol poisoning
146
What drug blocks acetaldehyde dehydrogenase ?
Disulfiram
147
What drugs have disulfiram-like reactions?
Metronidazole, certain cephalosporins, procarbazine, first generation sulfonylureas
148
Why do alcoholic patients end up with severe hypoglycemia?
THe liver will preferentially metabolize ethanol than do gluconeogenesis. So the liver needs to make more NAD+ so it can keep metabolizing alcohol.
It will metabolize pyruvate to lactate and oxaloacetate to malate which both reactions will regenerate NAD+ from NADH
149
What is kwashiorkor?
Protein malnutrition
150
A patient has skin lesions, edema, depigmentation of skin and hair, liver malfunction and a swollen belly. what are they malnourished in?
This is Kwashiorkor, protein malnutrition.
THe patient has liver dysfunction because they have decreased apoB100 so you get fatty liver because the triglycerides can't leave the liver
151
what is Marasmus?
Energy malnutrition
152
A patient presents with tissue and muscle wasting, loss of subcutaneous fat and variable edema. what do they have?
Marasmus - malnutrition
153
What's the rate determining enzyme of glycolysis?
Phosphofuctokinase - 1
154
What's the rate determining enzyme of gluconeogenesis?
Fructose- 1, 6 bisphosphatase
155
What's the rate determining enzyme of TCA cycle?
Isocitrate dehydrogenase
156
What's the rate determining enzyme of Glycogen synthesis?
Glycogen synthase
157
What's the rate determining enzyme of Glycogenolysis?
Glycogen phosphorylase
158
What's the rate determining enzyme of HMP shunt?
Glucose-6-phosphate dehydrogenase
159
What's the rate determining enzyme of de novo pyrimidine synthesis?
Carbamoyl phosphate synthestase 2
160
What's the rate determining enzyme of de novo purine synthesis?
Glutamine - PRPP amidotransferase
161
What's the rate determining enzyme of urea cycle?
Carbamoyl phosphate synthetase 1
162
What's the rate determining enzyme of fatty acid synthesis?
Acetyl-CoA carboxylase
163
What's the rate determining enzyme of fatty acid oxidation?
Carnitine acyltransferase I
164
What's the rate determining enzyme of ketogenesis?
HMG-CoA synthase
165
What's the rate determining enzyme of Cholesterol synthesis?
HMG-CoA reductase
166
how many ATP can RBCs generate per glucose molecule?
2 net ATPs since RBCs can only do anaerobic glycolysis
167
Where is the enzyme glucokinase found?
Liver and beta cells of the pancreas
| glucokinase is induced by insulin
168
what two enzymes are responsible for phosphorylating glucose to glucose-6-phosphate?
Glucokinase and hexokinase
169
what does arsenic inhibit and why is that important?
Arsenic inhibits lipoic acid which is one of the 5 cofactors needed for the pyruvate dehydrogenase complex
170
What findings would you see in a patient with arsenic poisoning?
Garlic breath, vomiting, rice water stools
171
what are the 4 different pyruvate metabolism pathways?
1. alanine aminotransferase +Vit B6 turning pyruvate into alanine to carry amino groups to the liver from muscle
2. Pyruvate carboxylase + biotin to make oxaloacetate to replenish the TCA cycle or be used in gluconeogenesis
3. Pyruvate dehydrogenase with B1, 2, 3, 5 and lipoic acid) to transition from glycolysis to the TCA cycle
4. Lactic acid dehydrogenase + B3 for the end of anaerobic glycolysis
172
What aer the three irreversible enzymes used in the TCA cycle?
1. citrate synthase
2. isocitrate dehydrogenase
3. alpha ketogluterate dehydrogenase
173
What drives the production of ATP in the mitochondria?
Passage of electrions making the proton gradient which is coupled to oxidative phosphorylation
174
Where does NADH come from?
HMP shunt
175
Why is NADPH important list 3 reasons?
1. Synthesizing FAs and cholesterol
2. generating O2 free radicals (to kill bacteria in phagocytes)
3. protect RBCs from O2 free radicals
176
Where does the HMP shunt (pentose phosphate pathway) occur?
lactating mammary glands
liver
adrenal cortex (sites of FA or steroid synthesis)
RBCs
177
Patients with WBCs that can utilize H2O2 generated by invading organisms and convert it to reactive oxygen intermediates but are susceptible to catalase positive species due to their ability to neutralize their own H2O2 leaving the WBCs without ROIs for fighting infections.
Chronic granulomatous disease
178
what enzyme is deficient in patients with chronic granulomatous disease?
NADPH oxidase
179
what cells utilize the respiratory burst (oxidative burst)?
monocytes, neutrophils
180
what reactive oxygen intermediate used in respiratory burst to attack bacteria?
bleach or hypochlorite
181
What is necessary to keep glutathione reduced?
NADPH
182
A patient presents with non-immune intravascular hemolytic anemia after eating fava beans, sulfonamides, primaquine, and antiTB drugs, what are they deficienct in?
This all is causing oxidative stress. the patient is deficient in glucose-6-phosphate dehydrogenase
183
A patient has oxidized hemoglobin precipitated within RBCs, what is this and what is she deficient in?
These are Heinz bodies. the patient has G6PD deficiency
184
When do you see Bite cells?
Bite cells result from the phagocytic removal of Heinz bodies by splenic macrophages
This is seen in GCPD deficiency
185
What's the big deal with G6PD?
```
G6PD is used to regenerate NADH which is a reducing agent which is used by glutathione reductase to keep glutathione reduced
Reduced glutathione (2 GSH) is an important antioxidant in RBCs!!
```
186
A patient presents with an AR defect and they have increased fructose in their urine and blood. What is the disorder, defect and why aer there not severe symptoms?
This patient has essential fructosuria
This is a defect in fructokinase.
Fructose builds up but it isn't trapped in cells, so it just spills over into the urine
187
A patient presents with an AR defect with hypoglycemia, jaundice, cirrhosis, and vomiting. Their symptoms are much worse after they eat fructose or sucrose. What is the disorder and the defect?
This patient has fructose intolerance due to a deficiency of aldolase B
This causes fructose-1-phosphate to accumulate leading to a decrease in available phosphate which results in inhibition of glycogenolysis and gluconeogenesis.
so you use up all the phosphate because it's all bound to fructose
188
what is the treatment of fructose intolerance?
decrease intake of both fructose and sucrose (glucose + fructose)
189
A patient presents with galactokinase deficiency - what do you expect to see?
This deficiency causes glactitol accumulation if galactose is present in the diet. it's relatively mild. AR
Galactose will appear in blood and urine, you can have infantile cataracts - may initially present as failure to track objects or to develop a social smile
190
A patient is diagnosed with classic galactosemia, what enzyme is deficient?
Galactose-1-phsophate uridyltransferase
serious defects can lead to PO4 depletion
191
A patient presents with an AR disorder with failure to thrive, jaundice, hepatomegaly, infantile cataracts, and mental retardation.
Classic galactosemia
192
What is the treatment for classic galactosemia?
Exclude galactose and lactose (galactose + glucose) from diet
193
in classic galactosemia, what accumulates in the eye?
galactitol accumulates in the lens of the eye
194
what is an alternative method of trapping glucose in the cell that converts it to its alcohol counterpart?
Sorbitol via aldose reductase
195
What enzyme does the liver, lens of the eye, ovaries and seminal vesicles have that other cells don't?
Sorbitol dehydrogenase, which converts sorbitol into fructose
196
Which cells only have aldose reductase?
schwann cells, retina and kidneys have only aldose reductase so they can only make sorbitol and not fructose
197
what's the problem with increased sorbitol levels?
Sorbitol accumulates intracellularly and acts as an omsole causing osmotic damage
- cataracts, teinopathy and peripheral neuropathy are seen with chronic hyperglycemia in diabetics
198
A patient presents with bloating, cramps and osmotic diarrhea after eating lactose - what's wrong with them?
Lactase deficiency - due to loss of brush border enzyme, may also follow gastroenteritis
treatment is to avoid dairy products or add lactase pills to the diet.
199
Can a patient that is lactase deficient eat galactose?
YES! you only need to avoid lactose, the patient does not have to avoid galactose
200
What is the mnemonic for essential amino acids?
PVT TIM HaLL
| Phe, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, Lyscine
201
What are the acidic amino acids?
Asp and Glu
note that these are NEGATIEVLY charged at the body's pH
202
What are the basic amino acids?
Argining, lysine, histidine
Note that these are POSITIVELY charged at the body's pH
203
what amino acids are used to transport ammonia?
Alanine and glutamate
204
A patient presents with hyperammonemia - what is the result of this?
Results in XS NH4+, which depletes alpha-ketogluterate leading to inhibition of TCA cycle
205
What would ammonia intoxication look like?
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
206
What is the treatment for a patient with hyperammonemia?
- Limit protein in diet
- Benzoate or phenylbutyrate (both of which bind to amino acid and lead to excretion) may be given to decrease ammonia levels.
- Lactulose to acidify the GI tract and trap NH4+ for excretion
207
a patient presents with increased orotic acid in their blood and urine, decreased BUN, and symptoms of hyperammonemia. What is this?
Ornithine transcarbamoylase deficieny
X linked recessive. This is the most common urea cycle disorder. Interferes with the bodies ability to eliminate ammonia
208
what is the catecholamine synthesis and enzymes used?
- Phenylalanine to tyrosine via phenylalanine hydroxylase
- Tyrosine to Dopa via tyrosine hydroxylase
- Dopa to Dopamine via dopa decarboxylase
- Dopamine to norepinephrine via Dopamine beta-hydroxylase
- norepinephrine to epinephrine via phenylethanolamine N-methyltransferase
209
what enzyme is deficient in PKU?
phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU)
210
A pt presents with MR, growth retardation, seizures, fair skin, eczema, and musty body odor - what is this?
Phenylketonuria, AR - they will be screened 2-3 d after birth once moms enzymes are no longer high
211
How do you treat PKU?
Decreased phenylalanine (contained in aspartame) and increased tyrosine in diet
212
What causes maternal PKU and what findings are seen in the infant?
Maternal PKU is caused by lack of proper dietary therapy during pregnancy
Findings in infant: microcephaly, mental retardation, growth retardation, congenital heart defects
213
what causes a congenital deficiency of homogentisic acid oxidase?
Alkaptonuria (ochronosis)
214
What is messed up in Alkaptonuria?
The patient can't degrade tyrosine to fumarate.
| AR
215
A patient presents with dark connective tissue, brown pirgmented sclera, and their urine turns black on prolonged exposure to air. They also may have debilitating arthralgias - what might this be?
Alkaptonuria
The arthralgia is because homogentisic acid is toxic to cartilage
216
what 3 things can lead to albinism?
1. lack of migration of neural crest cells (no melanocytes)
Congenital deficiency of either of the following:
2. tyrosinase - inability to synthesize melanin from tyrosine -- AR
3. Defective tyrosine transporters
Variable inheritance due to locus heterogeneity!
217
a patient presents with increased homocysteine in the urine, MR
The patient has homocystinnuria
218
What are the 3 forms (all AR) of homocystinuria and the treatments?
1. Cystathionine synthase deficiency - treat by decreased methionine and increased Cys and B12 and folate in diet
2. decreased affinity of cystathionine synthase for pyridoxal phosphate - treat by increasing vit B6
3. deficiency in homocysteine methyltransferase - treat with vit B12
219
A patient presents with cystinuria - what amino acids are they unable to transport in the PCT of the kidney?
Cysteine, ornithine, lysine, and arginine
220
what do you have excess of in cystinuria and what does it lead to?
increased cystine in the urine can lead to precipitation of hexagonal crystals and renal staghorn calculi
221
How can you treat Cystinuria?
good hydration and urinary alkalinization
you can use acetazolamide to alkalinize the urine
222
What is cystine?
Cystine is 2 cysteines connected by a disulfide body
223
What is the defect in maple syrup urine disease?
Blocked degradation of branched amino acids (Isoleucine, leucine, valine) due to decreased alpha ketoacid dehydrogenase (Vit B1)
AR
224
What are the findings in maple syrup urine disease?
- increased alpha ketoacids in the blood (especialy leucine)
- Severe CNS defects, mental retardations and death
- urine smells like maple syrup
225
What is Hartnup disease?
AR disorder defective neutral amino acid transporter on renal and intestinal epithelial cells
226
A patient presents with tryptophan excretion in urine and decreased absorption from the gut - leads to pellagra; what is the disease?
Hartnup disease
This leads to pellagra because without tryptophan you can't make niacin (Vit B3)
227
What messenger does glucagon stimulate to have it's affect?
glucagon stimulates adenylyl cyclase therefore increasing cAMP and activating PKA
228
What linkages does glycogen synthase make?
Glycogen synthase makes alpha 1, 4 glycosidic linkages
229
what linkages does branching enzyme make?
Branching enzyme makes alpha 1, 6 glycosidic linkages
230
What is the mnemonic for glycogen storage diseases?
Very Poor Carbohydrate Metabolism
```
Von gierke's disease (type 1)
Pompe's disease (type 2)
Cori's disease (type 3)
Mcardles disease (type 5)
```
231
A patient presents with severe fasting hypoglycemia, increased glycogen in the liver, increased blood lactate and hepatomegaly, what is the disease?
Von Gierke's disease
232
A patient presents with cardiomegaly and systemic findings leading to early death what is the disease?
Pompe's disease
Pompe's trashes the Pump -- heart, liver, muscle
233
A patient presents with a milder form of Von Gierke's disease with normal blood lactate levels. what's the disease?
Cori's disease
234
A patient presents with increased glycogen in muscle, but can't break it down, leading to painful muscle cramps, and myoglobinuria with strenuous exercise. What is the disease?
McArdles disease
235
A patient presents with an AR disease and they are deficient in Glucose 6 phosphatase - what is the disease?
Von Gierke's disease
236
A patient presents with an AR disease and they are deficient in lysosomal alpha 1, 4 glucosidase (acid maltase). What is the disease?
Pompe's disease
237
A patient presents with an AR disease and they are deficient in debranching enzyme (alpha 1, 6 glucosidase) - what is the disease?
Cori's disease
note that gluconeogenesis is intact
238
A patient presents with an AR disease where they are deficient in skeletal muscle glycogen phosphorylase - what is the disease?
McArdles Disease
239
What are the lysosomal storage diseases that are X linked Recessive?
Hunter's syndrome and Fabry's disease
240
What are the lysosomal storage diseases that are AR?
Gaucher's, Niemann-Pick, Tay-Sachs, Krabbe's, Metachromatic leukodystrophy, Hurler's
241
A patient is deficient in alpha galactosidase A enzyme and is accumulating ceramide trihexoside - what is their lysosomal storage disease?
Fabry's disease
242
A patient is deficient in the Glucocerebrosidase enzyme and is accumulating glucocerebroside - what is their lysosomal storage disease?
Gaucher's disease
243
A patient is deficient in sphingomyelinase enzyme and is accumulating sphingomyelin - what is their lysosomal storage disease?
Niemann-Pick disease
244
A patient presents with a deficiency in the enzyme Hexosaminidase A and is accumulating GM2 ganglioside - what is their lysosomal storage disease?
Tay Sachs disease
245
A patient is deficient in Galactocerebrosidase enzyme and is accumulating Galactocerebroside - what is their lysosomal storage disease?
Krabbe's disease
246
A patient is deficient in the enzyme Arylsulfatase A and is accumulating Cerebroside sulfate - what is their lysosomal storage disease?
Metachromatic leukodystrophy
247
A patient is deficient in the enzyme alpha - L- iduronidase and is accumulating Heparan sulfate and dermatan sulfate - what is their lysosomal storage disease?
Hurler's syndrome
248
A patient is deficient in the enzyme iduronate sulfatase and is accumulating heparin sulfate and dermatan sulfate - what is their lysosomal storage disease?
Hunter's syndrome
249
A patient presents with peripheral neuropathy of their hands and feet, angiokeratomas, cardiovascular and renal disease - they may also have painless papules on their lower abdomen, butt and groin. What is their disease?
Fabry's disease
250
A patient presents with Hepatosplenomegaly, aseptic necrosis of their femur, bone crises, anemia, thrombocytopenia, fatigue and macrophages that look like crumpled up tissue paper
Gaucher's Disease
251
What are Gaucher's cells?
Macrophages that look like crumpled tissue paper
252
A patient presents with progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on their macula, and foam cells. They will die by age 2-3, they have ataxia due to accumulation in cerebellum, dysarthria, dysphagia, gradual decrease in myelin function. What is their disease?
Niemann pick disease
253
A patient presents with progressive neurodegeneration, developmental delay, cherry-red spot on macula lysosomes with onion skin, may have vision and hearing difficulties. What is their disease?
Tay-Sachs disease
254
A patient presents with peripheral neuropathy, developmental delay, optic atrophy and globoid cells. What is their disease?
Krabbe's disease
255
A patient presents with central and peripheral demyelination with ataxia, and dementia. What is their disease?
Metachromatic leukodystrophy
256
A patient presents with developmental delay, gargoylism, airway obstruction, corneal clouding and hepatosplenomegaly. What is their disease?
Hurler's syndrome
257
A patient presents with mild Hurler's and aggressive behavior, no corneal clouding. What is their disease?
Hunter's syndrome
258
What is carnitine deficiency?
The inability to transport long chain FAs into the mitochondria, resulting in toxic accumulation.
causes weakness, hypotonia, and hypoketotic hypoglycemia
259
what is used by the CNS for energy during periods of PROLONGED starvation?
Beta-hydroxybutyrate
260
T or F: Urine tests for ketones like Beta-hydroxybutyrate
False - urine tests do look for ketone bodies but NOT for Beta-hydroxybutyrate - the urine tests only for acetoacetate
261
What conditions cause the overproduction of ketone bodies?
In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, XS NADH shunts oxaloacetate to malate
Both of these processes stall the TCA cycle which shunts glucose and FFA to the production of ketone bodies.
262
When a patient is starving, how long until their glycogen reserves are depleted?
1 day
263
what enzyme do statins block?
HMG-CoA reductase
264
which apoliprotein mediates remnant uptake?
Apolipoprotein E
265
which apoliprotein activates LCAT?
Apolipoprotein A-1
266
which apoliprotein functions as a lipoprotein lipase cofactor?
apolipoprotein C-11
267
which apoliprotein mediates chylomicron secretion (from enterocyte to lymphatic system)?
Apolipoprotein B-48
268
which apoliprotein binds LDL receptor which is necessary for when you leave the liver?
Apolipoprotein B-100
269
which lipoprotein delivers dietary TGs to peripheral tissue and delivers cholesterol to the liver in the form of chylomicron remnants, which are mostly depleted of their triacylglycerols. and is secreted by intestinal epithelial cells?
Chylomicrons
270
Which lipoprotein delivers hepatic TGs to peripheral tissue and is secreted by the liver?
VLDL
271
Which lipoprotein is formed in the degradation of VLDL and delivers triglycerides and cholesterol to the liver?
IDL
272
Which lipoprotein delivers hepatic cholesterol to peripheral tissues and is formed by hepatic lipase modification of IDL in the peripheral tissue. It's also taken up by target cells via receptor-mediated endocytosis.
LDL
273
Which lipoprotein mediates reverse cholesterol transport from the periphery to the liver, acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism) and is secreted from both the liver and the intestines?
HDL
274
Which familial dyslipidemia will cause an increased in chylomicrons, TG and cholesterol?
Type I - hyper-chylomicronemia
275
A patient presents with an AR disease with either lipoprotein lipase deficieny or altered apolipoprotein C-II. This leads to pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas. The patient has no increased risk for atherosclerosis.
Type I familial dyslipidemia - hyper-chylomicronemia
276
A patient presents with an AD disease with an absent or decreased LDL receptor causing accelerated atherosclerosis, tendon xanthomas and corneal arcus. What is this?
Type II familial dyslipidemia - familial hypercholesterolemia
IIa - defective LDL receptor
IIb - mutant apoB100
277
A patient presents with an AD disease with hepatic overproduction of VLDL causing pancreatitis. What does this patient have?
Type IV familial dyslipidemia - hyper-triglyceridemia
278
Which familial dyslipidemia will cause an increase in LDL and cholesterol?
Type II familial hypercholesterolemia
279
Which familial dyslipidemia will cause an increase in VLDL and TG?
Type IV - hyper-triglyceridemia
280
what lipoproteins are a patient deficient in with Abetalipoproteinemia?
B48 and B100 are deficient which leads to decreased chylomicron and VLDL synthesis and secretion
treating with Vitamin E helps to restore some of the lipoproteins
281
A patient presents with an AR disease with a mutation in microsomal triglyceride transfer protein (MTP) - what is this?
Abetalipoproteinemia
282
What symptoms are seen in Abetalipoproteinemia?
failure to thrive, steatorrhea, acanthocytosis (spikes on RBCs), ataxia and night blindness.
283
A patient presents with increased chylomicron remnants, increased VLDL and increased total cholesterol - what are they deficient in?
ApoE - this is a type III familial dysbetalipidemia
284
What is the defect in achondroplasia?
constitutive activation of FGF3 (cell signaling receptor)
| it isn't inactivated, its OVERLY activated!
