Biochemisty Flashcards
1
Q
What is the HH equation?
A
pH = pKa + log (base/acid)
2
Q
What is the equation that relates pCO2 to H2CO3?
A
0.03*pCO2 = H2CO3
3
Q
What is the modified HH equation for blood pH?
A
pH = [HCO3] / (0.03* pCO2)
4
Q
What is the normal pH range of blood?
A
7.35-7.45
5
Q
What is the equation for anion gap?
A
Na - (HCO3 + Cl)
6
Q
What is the normal range of the anion gap?
A
12 +/- 4
7
Q
What is the mnemonic for anion gap acidosis?
A
Methanol Uremia DKA Phenyl alcohol Isoniazid / Iron Lactic acid Ethanol Rhabdo Salicylates
8
Q
What is the mnemonic for non-anion gap acidosis?
A
H = hyperalimentation (e.g., starting TPN). A = acetazolamide use. R = renal tubular acidosis (Type I = distal; Type II = proximal; Type IV = hyporeninemic hypoaldosteronism. D = diarrhea U = uretosigmoid fistula (because the colon will waste bicarbonate). P = pancreatic fistula (because of alkali loss--the pancreas secretes a bicarbonate-rich fluid).
9
Q
What is represented by the anion gap?
A
Unmeasured anions
10
Q
What is the difference between a fixed and a volatile acid?
A
Fixed = cannot be blown off through the lungs
Volatile = can be
11
Q
What happens to the following with emphysema:
- pCO2
- HCO3
- pH
A
- Increased pCO2 (can’t blow off)
- Increased HCO3 (kidney compensation)
- Normal pH (maintained by the ratio)
12
Q
All polymerases add nucleotides from the 3’ or 5’ end? How do they progress along the strand (3’ to 5’ or vice versa)?
A
- 3’ end
- Move from 3’ to 5’
13
Q
What replaces the T in RNA?
A
Uracil
14
Q
What is the major start codon?
A
AUG (school starts in AUGust)
15
Q
What are the three major stop codons?
A
UGA (you go away)
UAA (you are away)
UAG (you are gone)
16
Q
the 5’ end of the DNA pairs with which side of the RNA?
A
3’
17
Q
The mRNA is almost identical to what DNA strand: sense or antisense strand?
A
Sense strand
18
Q
What, generally, are thalassemias?
A
Structural variants of Hb, that produce unstable Hb molecules
19
Q
What are the three major abnormal structural variants of Hb? What gene do they all impact?
A
- Hb S (sickle cell)
- Hb C (Hb C disease)
- Hb E (Hb E disease)
All impact the beta globin gene
20
Q
What chromosome is the beta globin gene found on?
A
11
21
Q
What is meant by the term Hb S (or Hb C, E, etc) trait?
A
One mutant allele of beta globin gene and one wild -type allele
22
Q
What is the amino acid change in sickle cell disease?
A
Glutamate at position 6 is exchanged for a valine (charge to uncharged amino acid)
23
Q
When does sickle cell Hb precipitate into solution?
A
When deoxygenated
24
Q
What is a sickle cell crises?
A
Severe bone pain precipitated by dehydration or infx
25
What is the medication that can be used to treat sickle cell anemia? How does it work?
- Hydroxyurea
| - Boosts Hb F (alpha2, gamma2)
26
What is Hb C disease? What ethnicity is this more common in ?
- Glutamate changes to lysine at position 6, causing form crystals (as opposed to polymerizing like with sickle cell dz)
- West african origin
27
Why don't patients with Hb C disease have episodic crises? What s/sx do they have?
Hb C does not polymerize-- form crystals that can cause splenomegaly or cholelithiais
28
How can you distinguish between Hb S and Hb C?
Electrophoresis
29
True or false: Hb C/s compound disease is relatively common
True
30
What is Hb E disease? What ethnicity is it found in?
- E to K at position position 26, causing not enough beta globin chain synthesis
- Southeast asia
31
What type of anemia does patients with Hb E disease? Mild or severe?
Mild microcytic anemia
32
What is the treatment for Hb E disease?
None needed--mild disease
33
What are the three major prion diseases?
- CJD
- vCJD
- Kuru
34
What are prions?
Proteinaceous infectious particle
35
What is the pathophysiology of prion disease?
Seeding and propagation of abnormal proteins
36
What is the protein change that occurs with prion diseases?
PrP^C changes to PrP^Sc
37
What is the inheritance pattern of CF?
AR
38
What is the defect in CF?
Defect In CFTR gene encoding a chloride channel
39
What is the diagnostic test for CF?
Increased NaCl in sweat
40
What is the most common mutation for CF? What does this cause?
- Deletion of a single phenylalanine residue at position 508
- Interferes with protein folding and glycosylation
- Mutant protein fails to route to the cell membrane
41
What is the inheritance pattern of HD?
AD
42
What is the trinucleotide repeat with HD? What protein is added to the gene?
- CAG
| - Adds glutamine residues and thus misfolded aggregates
43
What part of the brain is damaged with HD?
Caudate nucleus
44
What is the gene that is affected with HD?
Huntingtin (HTT disease)
45
What is the MM equation?
V = Vmax[S] / (Km = [S])
46
What does the Km value represent in the MM equation?
Represents the substrate concentration where v Vmax / 2
47
What are the neurotransmitters that are lost with HD?
Loss of ACh and GABA
| "Caudate loses ACh and GABA (CAG)"
48
Which is dependent on substrate concentration: Vmax or Km?
Vmax (Km is independent)
49
Does a large or a small Km indicate a high affinity for a substrate?
Small = higher affinity
50
What happens to Vmax and Km with competitive inhibitors?
Vmax is normal
| Km is shifted
51
What happens to Vmax and Km with non-competitive inhibitors?
Vmax is lower
| Km is unchanged
52
What is the modification that is made with non-competitive inhibitors of an enzyme?
Forms covalent bond that cannot be washed away
53
What is the difference in MOA of ASA vs IBU?
- ASA = irreversible COX inhibitor
| - IBU = reversible COX inhibitor
54
What are allosteric enzymes inhibitors? Do they follow MM kinetics?
- Enzymes with multiple subunits that exhibit positive / negative cooperativity (e.g. Hb tetramer)
- No
55
What is the MOA of diphtheria toxin?
ADP ribosylation of EF-2
56
How is the ribosomal subunit deactivated?
Phosphorylation of eIF2a
57
What is the MOA of pseudomonas?
ADP ribosylation of EF-2
58
What is the MOA of ricin?
Remove adenine bases from 28s rRNA
59
What is the MOA of shiga toxin?
Remove adenine bases from 28s rRNA
60
What is the abx that causes gray baby syndrome? How?
Chloramphenicol
| ***Cannot UDP***
61
Where does N and O linked glycosylation occur?
```
N = ER
O = Golgi
```
62
Where in the cell does trimming of N/O glycosylation occur?
Golgi
63
What is the pathophysiology of scurvy? Where in the cell does this occur?
Inability to hydroxylation of proline in the rER
64
What are the amino acids that are O linked glycosylated?
Y and S
65
What is Menke's disease?
***
66
What are congenital disorders of glycosylation?
Rare, protein losing enteropathy
67
What is prenylation? What proteins need this to become activated?
G-Ras proteins
68
What drugs inhibit isoprenoid synthesis?
Statins d/t loss of cholesterol
69
What is the signal on proteins that move proteins from the ER to the golgi?
Phosphorylation of Mannose
70
What is I cell disease?
Deficiency of Phosphorylation of mannose on glycoproteins leads to accumulation of undegraded molecules in the lysosomes
71
What is the difference between euchromatin and heterochromatin?
- Euchromatin = open to transcription
| - Heterochromatin = not open to transcription
72
Histone acetylation leads to what effect on transcription?
Facilitates transcription
73
DNA methylation leads to what effect on transcription?
Inhibits transcription
74
Where are enhancer / suppressor regions found in DNA?
Anywhere
75
Where are promoter elements found on DNA?
Near to, and just prior to the DNA region being transcribed
76
What are the different types of transcription factors?
- Steroid
- CREB
- PPAR
- NFkappaB
- Homeodomain proteins
77
What are CREB proteins/?
***
78
What are PPARs?
Peroxisome proliferator activated receptors that regulate lipid metabolism (activated by fibrates)
79
What are the HOX genes for?
Regulate development
80
What is the general role of NF-kappa-B?
Regulates gene expression in the immune system
81
What is the key regulatory step of gluconeogenesis? What stimulates it? (2)
- PEP carboxykinase
- Cortisol stimulates via cortisol receptor and
- Glucagon stimulates expression via cAMP / CREB
82
What are the steps involved with Gs? What is activated with the glucagon pathway?
Stimulates cAMP, and protein kinase A
CREB is activated
83
Which are short and which are long lived: water soluble vs lipophilic
```
Water = short lived
Lipid = long lived
```
84
Where is the receptor for water soluble hormones? Lipid hormones?
Water soluble = plasma membrane
Lipid = in the cytoplasm or nucleus
85
Which typically acts through a second messenger, or has enzymatic activity: water or lipid soluble
Water soluble for both
86
Which modulate the activity of enzymes, vs modulates the transcription of enzymes: water vs lipid soluble hormones
modulate the activity of enzymes = water soluble
modulates the transcription of enzymes = lipid soluble
87
What is the MOA of G proteins?
GDP bound alpha subunit of the G protein changes to GTP, and activates adenylate cyclase
88
What is the MOA of adenylate cyclase?
ATP to cAMP
89
What is the protein that is the target of Gs pathway?
Turns on PKA, which can phosphorylate phosphorylase kinase, which phosphorylates other stuff
90
What is the major advantage of Gs protein, as opposed to having a signal molecule directly activate PKA?
Signal amplification
91
What are the two second messengers of Gq pathway? What does each do?
- IP3 and DAG
| - DAG remains in plasma membrane, IP3 goes releases Ca from the sER
92
What is the MOA of PKC? How is it activated?
Ca released from the sER from IP3 leads to activation
93
What is the role of calmodulin?
Binds Ca and modulates Ca control
94
What is type of receptor is the insulin receptor? MOA?
- Protein tyrosine kinase
| - phosphorylates IRS1, which serves as a binding site for other molecules
95
What does CREB bind to?
CRE element on DNA
96
What is the function of B1 (thiamine)
- Decarboxylation of alpha-ketoacids
- Transketolase rxn
(alpha-KG dehydro, Transketolase, Pyruvate dehydrogenase)
97
What are the diseases that result from B1 deficiency?
- BeriBeri
| - Wernicke-Korsakoff syndrome
98
What are the physiological effects of Vit B1 deficiency?
Impaired glucose production
99
What are the s/sx of Beriberi?
- Pain and paresthesias
- Impaired cardiac energy metabolism
- Peripheral neuritis
100
What is the triad classic for Wernicke encephalopathy?
- Horizontal nystagmus
- Encephalopathy
- ataxia
- ophthalmoplegia
101
What is the classic triad for NPH?
wacky, wobbly and wet
102
What is B2 (riboflavin) needed for?
Component of FAD and FMN
103
What are the s/sx of riboflavin deficiency?
- Cheilosis
- Corneal vascularization
-Two C's of B2
104
What is Niacin (b3) used for?
Dehydrogenase reactions
| -NAD (B3 = 3 ATP)
105
What is the disease caused by niacin deficiency? S/sx?
Pellagra
- Dermatitis
- Dementia
- Diarrhea
- Death
106
Niacin can be synthesized from what amino acid? What does this synthesis require?
Tryptophan, which requires B6
107
What are the s/sx of excess niacin?
Facial flushing
108
What is the function of B5?
Required for amino acid metabolism and heme synthesis
109
What are the s/sx of B5 deficiency? (4)
- Dermatitis
- Enteritis
- alopecia
- Adrenal insufficiency
110
What are the hematological abnormalities that can be had with B5 deficiency?
Sideroblastic anemia
111
What is the function of B9 (folate)? (2)
- THF generation
| - *Thymidylate synthase*
112
Where is folate from?
Foliage
113
What are the s/sx of folate deficiency? Why?
- Macrocytic, megaloblastic anemia
| - Thymidylate synthase inhibition leads to inability to synthesize DNA
114
What are the only 2 reactions that B12 is needed for?
- Methionine synthase
| - Methylmalonyl-CoA mutase
115
What is the only source of B12?
Bacteria
116
What is the parasite that causes B12 deficiency?
Diphyllobothrium latum
117
What are the s/sx of B12 deficiency? (3)
- Demyelination of the dorsal columns
- Methylmalonic aciduria
- Megaloblastic anemia
118
How does B12 cause megaloblastic anemia?
Lack of B12 blocks methionine synthase rxn takes away the only reaction to convert N5-methylTHF to more oxidized forms
119
***
***
120
What is the most common cause of cobalamin deficiency?
Pernicious anemia, which causes a severe intrinsic factor deficiency
121
Where is B12 + IF absorbed in the intestines?
Ileum
122
What, besides the synthesis of collagen, is Vit C needed for?
Dopamine-beta-hydroxylase (converts Dopamine to NE)
123
What are the s/sx of excess vitamin C?
- n/v
- diarrhea
- fatigue
124
What is B7 (biotin) needed for?
Cofactor for the carboxylation
125
What is the protein in eggs that prevent biotin (B7) uptake?
Avidin
126
What is the disease that can result in biotin deficiency?
biotinidase deficiency
127
What are the s/sx of biotin deficiency?
- facial rash
- Alopecia
- Keto-lactic acidosis
- hypotonia
128
What can be detected in the urine with biotin deficiency?
3-hydroxyisovaleric acid
129
What is B5 needed for?
fat synthesis
| CoA synthesis
130
What are the s/sx of B5?
- Dermatitis
- enteritis
- alopecia
- Adrenal insufficiency
131
What is vitamin A required for?
- Retinaldehyde in vision
| - Retinoic acid as a hormone
132
What is the major source of vitamin A?
Beta-carotene in vegetables
133
What are the s/sx of vitamin A deficiency?
- Night blindness
- Xerophthalmia (keratinization of the cornea)
- Infections
134
What are the s/sx of acute vitamin A excess? (3)
- Increased ICP
- Szs
- Exfoliative dermatitis
135
What are the s/sx of chronic vitamin A excess? (4)
- Dryness of skin
- Alopecia
- Glossitis
- Cheilosis
136
What is the effect of excess vitamin A in pregnancy?
Birth defects and abortions
137
What is D2 and D3 respectively?
```
D2 = ergocalciferol
D3 = Cholecalciferol
```
138
What is the storage and active form of Vit D?
```
25-D = storage
1,25 = active
```
139
What are the s/sx of vitamin D excess?
Hypercalcemia
| Stones
140
Why is there excess Ca with sarcoidosis?
increased activation of macrophages
141
What is the name of vitamin E?
alpha tocopherol
142
What is the function of vitamin E?
antioxidant
143
What is the effect of vitamin E on WArfarin?
Increases effects
144
What are the s/sx of vitamin E deficiency?
Hemolytic anemia
| acantholysis
145
What is the function of vitamin K?
Synthesis of various clotting factors (carboxylation of glutamate residues in various proteins)
146
What is the primary source of vitamin K?
Green leafy vegetables
147
What are the s/sx of vitamin K deficiency?
neonatal hemorrhage with increased PT and PTT
| -Bleeding, bruising, hemorrhage
148
Why are neonates given vitamin K injections at birth?
They don't have intestinal flora that produces it yet
149
What causes warfarin necrosis?
Protein C and S are depleted fasters, causing a hypercoagulable state, and resulting necrosis
150
What is the MOA of warfarin?
Inhibits Vitamin K epoxidase
151
True or false: you cannot convert acetyl-Coa into glucose
True
152
What is the overall purpose of the CAC?
take acetyl-coa to NADH, FADH and GTP
153
What are the three major control points of the CAC?
- Citrate synthase
- Isocitrate dehydrogenase
- alpha-KG
154
What is citrate synthase controlled by?
availability of OXA
155
What is isocitrate dehydrogenase controlled by?
Activated by ADP and inhibited by NADH
156
What is alpha-KG dehydrogenase controlled by?
Inhibited by NADH and succinyl-CoA
157
What is the function of citrate?
-Exported to cytoplasm, and cleaved by citrate lyase to release acetyl-CoA for fat synthesis
158
What is the function of malate?
Exported to cytoplasm to serve as a substrate for gluconeogenesis
159
What is the function of succinyl-CoA?
Substrate for Heme synthesis
160
What is the drug that inhibits complex I of the ETC?
Rotenone (barbiturates)
161
What is the drug that inhibits complex III of the ETC?
Amtimycin
162
What is the drug that inhibits complex IV of the ETC?
Cyanide
163
What is the drug that inhibits ATP synthase of the ETC?
Oligomycin
164
What is the sequence of complexes in the ETC? (5)
```
I
CoQ
III
Complex C
IV
```
165
Where is NADH oxidized in the ETC?
Complex I
166
Where is FADH2 oxidized in the ETC?
Complex II
167
How many ATP are generated from NADH and FADH2 respectively?
2. 5 for NADH
| 1. 5 for FADH2
168
What is the treatment for CN toxicity? MOA?
Amyl Nitrate + sodium nitrite
-Nitrate oxidizes some of the Fe from ferrous to ferric state, to cause CN to release CN from Cytochrome oxidase
169
What is the MOA of dinitrophenol?
Uncoupler of ETC
170
What is the protein in brown fat the uncouples ETC?
Thermogenin
171
What is the major source of ROS in the ETC?
Ubiquinone
172
What is ischemia reperfusion injury?
Low ATP and high NADH after transient ischemia
