NOT M2P Flashcards
(111 cards)
1
Q
What are the isoprenoids?
A
Steroids, lipid vitamins, terpenes
2
Q
What are eicosanoids?
A
Prostaglandins, thromboxanes, leukotrienes
3
Q
What are the glycerophopholipids?
A
Ether phospholipids, platelet activating factor, plasmalogens, phasphatidates, shingomyelins
4
Q
What are the glycosphingolipids?
A
Cerbrosides, gangliosides, other GSL
5
Q
What are the phospholipids
A
PE, PC, PS, PI, other PLs
6
Q
Which FA is 14:0?
A
Myristic acid
7
Q
Which FA is 16:0?
A
Palmitic acid
8
Q
Which FA is 16:1?
A
Palmitoleic acid
9
Q
Which FA is 18:0?
A
Stearic acid
10
Q
Which FA is 18:1?
A
Oleic acid
11
Q
Which FA is 18:2?
A
Linoleic acid
12
Q
Which FA is 18:3?
A
Linolenic acid
13
Q
Which FA is 20:4?
A
Archidonic acid
14
Q
What does phospholipase A2 do?
A
Acts on PI releasing arachidonic acid–>prostaglandins
15
Q
What does phospholipase C do?
A
Activated by PIP2, so is involved with second messengers
16
Q
What does PGH synthase do?
A
converts Arachidonic acid –> PGH2 (prostaglandin)
COX1 - constitutively-expressed in most tissues
COX2 - induced by cytokines associated with inflammatory response
17
Q
What is the purpose of aspirin?
A
Inhibition of COX1/2, irreversible inhibitor of COX1, reversible inhibitor of COX2
18
Q
Which inhibitors are used for asthma?
A
Inhibitors of 5-LOX and antagonists of CysLT1 receptor
19
Q
Where does cholesterol come from?
A
De novo - 70%
Dietary - 30%
20
Q
What is the committed, rate limited step of cholesterol de novo synthesis?
A
HMG COA reductase, uses 2NADPH
Target for Statin drugs
21
Q
What does Farnesyl PP give rise to?
A
Dolichol, Ubiquinone, Prenylated proteins, Squalene
22
Q
What is 7-dehydrocholesterol?
A
Precursor for Vit. D
23
Q
How is HMG COA reductase regulated?
A
- Transcription factor SREBP-2 binding to the sterol regulatory element, SREBP-2 is associated with SCAP, when high [sterol], SCAP binds Insig, causing retention
- When high [sterol], HMGCoA reductase ubiquitination and proteosomal degredation
- HMG CoA reductase is -P by AMPK (inactive)
24
Q
How is HMGCoA reductase upregulated?
A
By decreased cAMP levels by insulin, and increased thyroxine
25
What is the rate limited step in bile acid production?
Introduction of -OH group at C7 by cholesterol-7-alpha-hydroxylase
26
What is characteristic of 3-beta-hydroxysteroid dehydrogenase deficiency?
Virtually no glucocorticoids, mineralocorticoids, active androgens, or estrogens, salt excretion in urine, female-like genitalia
27
What is characteristic of 17-alpha-hydroxylase deficiency
No sex hormones or cortisol, increased production of mineralocortioids causes NA and fluid retention, and hypertension, female-like genitalia
28
What is characteristic of 21-alpha-hydroxylase deficiency?
Mineralocoricoids and glucocorticoids are virtually absent, salt wasting, overproduction of androgens leads to masculinization of external genitalia in females and early virilization in males
29
What is characteristic of 11-beta1-hydroxylase deficiency?
decrease in serum cortisol, aldosterone, and coricosterone, increased production of deoxycortisosterone causes fluid retention, low-renin hypertension, causes masculinization and virilization
30
Which apolipoproteins is not associated with HDL?
Apo B
31
Which apolipoproteins are associated with LDL-R?
ApoE, ApoB100
32
What is the purpose of chylomicrons?
Assembled in intestinal mucosa and carry dietary triglycerides, cholesterol, and cholesteryl esters, fat-soluble vitamins and other lipids to peripheral tissues
33
Which apolipoprotein is specific for CM?
ApoB48
34
Which protein loads apoB48 with lipid and what is the AR disorder associated with it?
Microsomal triacylglycerol transfer protein (MTP), and abetalipoproteinemia is a mutation in MTP leading to steatorrhea and fat-soluble vitamin deficiency
35
Which enzyme is anchored to the membrane of endothelial cells of capillaries in most tissues? which tissue is the exception?
EXCEPT LIVER, Lipoprotein lipase, activated by apo C-II to hydrolyze TAG -> glycerol + FA
36
What causes hyperlipoproteinemia type I?
Defect in Lipoprotein lipase or apo CII leading to accumulation in CM
37
What is a means of regulation for LDL-R function?
Serine protease PCSK9 blocking LDL-R recycling to the cell surface
38
What is characteristic of familial hypercholesterolemia (FH)?
Genetic defects in the LDL pathway leading to the accumulation of LDL in the plasma, including mutated LDL-R, ApoB, PCSK9
39
What is the friedewald equation to estimate LDL-chol?
Total Chol = HDL + TG/5 + LDL-chol
40
What is the major difference between myoglobin (Mb) and hemoglobin (Hb)?
Myoglobin helps diffuse O2 in the cells while Hb is the major transporter of O2 from the lungs to tissues
-Hb participates in Cooperative binding (once 1 binds its easier for the rest to bind)
41
which molecule is bound to Hb in the ferrous form?
Oxygen
42
Which molecule is bound to Hb in the ferric form?
Water
43
Where is the primary organs where myoglobin is found?
Heart and muscle
44
What is meant by P50?
When half of the O2 binding sites within the hemeglobin is full, normally 26 Torr
45
According to Bohr what increases O2 release?
A rightward shift (increase CO2, increase Acid H+, lowering PH) thereby reducing the affinity for O2 and increases likelihood to release O2
46
Binding of what stabilizes the T form of Hb?
CO2, a little more than 10% of the body's CO is expelled via Hb
47
What will an increase in 2,3 BPG cause>
A stabilization of the deoxy state (T) and reducing the affinity for O2
48
What would happen if there wasn't any BPG?
The Heme would have a greater affinity for the Oxygen and would not release it in the tissues
49
What happens with increased temperature or increased CO?
Increased temp, better release of O2
| Increased CO, less release of O2
50
What is characteristic of fetal Hb?
HbF has a greater affinity for O2 than HbA. The gamma chain of HbF has a much lower affinity for 2,3BPG leading to a leftward shift to aid in getting O2 from Mom
51
Which hemoglobinopathies are associated with erythrocytosis versus anemia?
Rightward shift = anemia (Hb Titusville)
| Leftward shift = erythrocytosis (HB helsinki)
52
What is characteristic of methemoglobinemia?
Inherited enzyme deficiency of NADH-methemoglobin reductase enzyme that reduces Fe3 (ferric) to the Fe2 (ferrous) form. The patient presents with a blue skin tone and brown blood
53
Where does synthesis of heme occur?
In all cells except mature RBC
54
What is the rate controlled enzyme in heme synthesis?
ALA synthase, which combines Glycine and succinyl CoA with the coenzyme PLP to become ALA + CO2
OCCURS IN THE MITOCHONDRION
55
What is the main difference between Uroporphyrin I and Uroporphyrin III?
The location of propionic acid versus methyl groups coming off of 7/8 on the porphyrin,
UroI - 7 = A, 8=P
Uro III - 7 = P, 8=A
56
What is the main difference between Coproporphyrin I and coproporphyrin III?
Copr I - 7 = M, 8=P
| Copr III - 7 = P, 8=M
57
How is ALAS-II (erythroid) regulated?
Translation of mRNA controlled by iron, as iron availability increases, translation increases
58
How is ALAS-I (hepatic) regulated?
Translation of mRNA inhibited when high [heme]
| -High [heme] inhibits transport of ALAS-I into mitochrondria, and catalytic activity via feedback inhibition
59
What compounds induce ALAS-I?
Barbiturates, xenobiotics, increase P450 in the liver
60
Which enzyme is inhibited by lead?
- Porphobilinogen synthase (replaces Zn)/ALA dehydrogenase
| - Ferrochelatase
61
What are porphyrias and where do the different types accumulate?
- Porphyrias - defects in heme synthesis
- Non-erythropoietic accumulates in liver
- Erythropoietic - accumulates in bone marrow
62
What is characteristic of acute intermittent porphyria (AIP)?
- non erythropoietic (acute)
- affects hydroxymethylbilane synthase (decreased) and ALA synthase (increased)
- Effects the nervous system
63
What is characteristic of porphyria cutanea tarda (PCT)?
Non-erythropoietic (chronic)
- affects uroporphyrinogen decarboxylase (decreased) and ALA synthase (increased)
- Effects skin; can be induced by liver disease, discolored urine
64
What is characteristic of Lead poisoning?
- Affects all tissues
- Affects ALA dehydratase (decreased), ferrochelatase (decreased), and ALA synthase (increased)
- presents in the nervous system; blood (anemia)
65
What is measured in UCB versus CB blood test?
UCB measures the "free" bilirubin bound to albumin - Total bilirubin - CB = UCB
-CB measures the Bilirubin diglucuronide (direct)
66
What is hyperbilirubinemia?
An increase of bilirubin above 0.1-1.0 mg/dL
67
How does hyperbilirubinemia occur?
1. excessive production of bilirubin (prehepatic)
2. disturbance in conjucation (hepatic)
3. Interference in excretion (hepatic or post hepatic
68
What is associated with an excessive production of bilirubin and what would happen to the UCB value?
Hemolytic jaundice, sickle cell anemia, G6PD deficiency, PK deficiency, UCB increases in blood
69
What is associated with a decrease or absence of conjugation and what would happen to the UCB value?
Physiological jaundice, Crigler-Najjar (I/II), Gilberts disease, liver damage, increase in blood UCB
70
What is associated with inhibition of excretion of CB and what happens to the CB value in blood and UCB?
Dubin-johnson syndrome, increase CB in blood, urinary CB will increase and intestinal CB decrease (pale poop, dark urine)
71
How is iron lost?
Not excreted from the body in a regulated manner, loss through exfoliation
72
What are the 5 iron binding proteins and where are they found?
1. Apoferritin (most tissues) when bound is ferritin
2. Transferrin (blood) for transport
3. Lactoferrin - binds iron for uptake
4. Mobilferrin (intestinal cells) intracellular transport
5. Mitoferrin - across inner mito membrane`
73
Why do antiacids affect iron absorption?
The iron is transported via a symport H+ from the intestinal lumen to the enterocyte
74
What is the critical control of iron homeostasis?
Transport of Fe2+ out of enterocytes by ferroportin controlled by Hepcidin
75
How is hepcidin synthesis controlled?
In iron excess, hepcidin synthesis is increased leading to a decrease in ferroportin and decreased release of iron from enterocyte
-In iron deficiency hepcidin synthesis decreased, increased release of iron
76
What is associated with hereditary hemochromatosis?
Iron overload in liver, heart, and other organs usually in ferritin and hemosiderin. "Bronze diabetes"
-Defects in high iron gene (HFE)
77
How is [apoferritin] controlled?
IRE at the 5' end, so when low iron, IRP is bound stopping mRNA synthesis
- IRPs are degraded when [iron] is high
78
How is the transferrin receptor controlled?
IRE at the 3' end, so when low [iron] IRPs are available stabilizing mRNA and increases receptor concentration
79
How does iron affect ALAS II?
IRE at the 5' end, when high [iron] mRNA synthesis occurs (IRPs getting degraded)
80
What are the 5 steps of clotting?
1. formation of a fibrin clot
2. formation of a platelet plug
3. vasoconstrictions
4. anticoagulation
5. clot dissolution
81
How are proteins activated in the various clotting pathways?
1. Proteolytic cleavage (serine proteases)
| 2. Conformation change (no proteolysis)
82
What post-transcriptional modification is important in clotting? What drug targets this reaction?
gamma-carboxylation in the lumen of RER in liver
- Vit K is coenzyme
- Dicumarol and Warfarin (Coumadin) targets Vit K epoxide reductase
83
What is the key protein in the extrinsic pathway?
Transcription factor (III) which binds VII
84
Which protein is not associated with bleeding when it is deficient?
XII
85
Which deficiency is associated with hemophilia A and hemophilia B
```
A = VIII
B = IX
```
86
What mutation in which gene leads to increased tendency to clot?
G20210A in the prothrombin gene increases expression and increased clotting
87
Which factors are serine proteases?
II, VII, IX, X, XI, XII
88
Which factors are Gla-containing proteases?
II, VII, IX, X
89
Which factors are accessory proteins?
III, V, VIII
90
What is associated with Bernard-soulier syndrome?
Deficiency in platelet receptor for VWF
91
What do fibrinogen molecules do?
Link activated platelets to one another
92
What is associated with Glanzmann's thrombasthenia?
Defect in platelet receptor for fibrinogen
93
What is most important in limiting clotting?
Antithrombin III made by liver, which is a SERPIN, inactivating thrombin, IXa through XIIa, and VIIa-TF, greatly increased by heparin
94
Other than AT3 what limits clotting?
Protein C-S complex inactivates VIIIa and Va, and Tissue factor pathway inhibitor
95
What is characteristic of thrombophilia?
Deficiencies of proteins C, S, or anti thrombin III, presence of factor V leiden, and excess prothrombin
96
What is a tumor defined as?
a tumor is a heritably altered, relatively autonomous growth of tissue
97
What are the 6 characteristics of cancer?
1. Self sufficient GFs
2. Insensitive to antiGFs
3. Evasion of Apoptosis
4. Immortal
5. Angiogenesis
6. Tissue invasion and metastasis
98
Which protein is a powerful tumor supressor, how does it perform this function and when inhibited, how is it restored?
Retinoblastoma (Rb), sequesters E2F. Cyclin dependent kinase phospohrylates Rb unleashing E2F (^growth), and TFG-beta restores Rb
99
What gene induces apoptosis?
p53, more than 50% of human cancers has inactive p53
100
What is the most useful test in detecting carcinogens?
Ames Test
101
Which factor in inflammation inhibits apoptosis?
Prostaglandin (PGE2)
102
How are viruses carcinogenic?
HPV: The early genes E6, E7 sequester p53, and Rb
SV40: Early protein T antigen sequesters p53 and Rb
103
What is an example of an transducing RNA virus?
Insert viral oncogenes ex: Src, when transduced v-src. Has a tyrosine kinase activity -P various target genes part of growth/differentiation/migration
From the rous sarcoma virus
104
What is an example of a non-transducing cis-acting RNA virus?
Avian Leukosis Virus, ALV
| process referred to as promoter insertion
105
What is an example of a non-transducing trans-acting RNA virus?
Human t-cell leukemia virus type I (HTLV-I)
| trans-regulating protein Tax activates transcription
106
What is associated with common hyperlipidemia IIa?
AKA: Familial hypercholesterolemia
| High [LDL], high plasma [Chol]
107
What is associated with hyperlipidemia III?
AKA Dysbetalipoproteinemia
| High "floating" [LDL], high plasma [chol & TG], defect in receptor ApoE
108
What is associated with hyperlipidemiaV?
Elevated [VLDL & CM], elevated plasma [TG]
| either a LPL deficiency or ApoC-II deficiency
109
What is associated with hyperlipidemia I?
Elevated [CM], elevated plasma [TG]
| either a LPL deficiency or ApoC-II deficiency
110
what is characteristic of abetalipoproteinemia?
Virtual absence of apoB-containing lipoproteins
decreased plasma [TG/TC]
due to molecular abn in MTP involved in lipidating apoB
111
What is characteristic of Tangier disease?
Virtual absence of HDL
| defect in plasma membrane ABC transporter
