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Biochem > Ch 44 > Flashcards

Ch 44 Flashcards

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1
Q

What regenerates NAD+ in RBCs

A

lactate production

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2
Q

What is NADH used for in RBCs

A

reduce ferric form of hemoglobin

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3
Q

what is the ferric form of hemoglobin called

A

methemoglobin

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4
Q

what is the major allosteric effector for oxygen binding to hemoglobin

A

2, 3-biphosphoglycerate (2, 3-BPG); produced via side pathway of glycolysis

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5
Q

hexose monophosphate shunt

A

generates NADPH to protect RBCs membrane lipis and proteins from oxidation through regeneration of reduced glutathione

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6
Q

what does heme originate from

A

succinyl coenzyme A and glycine

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7
Q

porphyrias

A

mutations in any of the steps of heme synthesis

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8
Q

polymorphonuclear leukocytes

A

granulocytes; neutrophils, eosinophils, and basophils

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9
Q

mononuclear leukocytes

A

lymphocytes (B-cells, T-cells, NK cells) and monocytes

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10
Q

how do the different granulocytes stain

A

neutrophils pink, eosinophils red, basophils blue

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11
Q

respiratory burst

A

initiated by neutrophils, creates oxygen radicals that rapidly destroy forgein materials found at site of infection

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12
Q

eosinophil granules

A

contain hydrolytic enzymes and cationic proteins which are toxic to parasitic worms

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13
Q

basophil granules

A

histidine/histamine (allergic response), proteases, B-glucuronidase, and lysophospholipase; degrade microbial structures and assist in remodeling damaged tissue

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14
Q

how are different subclasses of T-cells identified

A

surface membrane proteins; correlate with fxn

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15
Q

Fxn of B-cells

A

secrete antibodies in respponse to antigen binding

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16
Q

Fxn of NK cells

A

target virally infected and malignant cells for destruction

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17
Q

MCV

A

average volume of RBC (80-100 fL)

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18
Q

MCHC

A

average concentration of hemoglobin in each individual erythrocyte (32-37 g/L)

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19
Q

What is ATP used for in RBCs

A

ion transport, phosphorylation of membrane proteins, priming rxns of glycolysis

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20
Q

rapaport-luebering shunt

A

glyclysis uses to generate 2, 3-BPG

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21
Q

what is 2, 3-BPG used for in other cells

A

required for phosphoglycerate mutase rxn of glycolysis; regenerated during each rxn, so only trace amounts required in most cells (except RBCs)

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22
Q

what occurs in pyruvate kinase deficiency

A

1/2 ATP formed in glycolysis compared to normal; tend to gain Ca++ and lose K+ and water

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23
Q

How are anemia affects moderated in pyruvate kinase deficiency

A

increased 2, 3-BPG concentration makes RBCs in circulation highly efficient in realeasing O2 to tissue

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24
Q

What state must iron be in hemoglobin to bind O2

A

ferrous (+2) state

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25
NADH-cytochrome b5 methemoglobin reductase system
cytochrome b5 reduces Fe3+, then oxidized cytochrome b5 is reduced by flavin-containing enzyme using NADH as the reducing agent
26
enzyme that catalyzes first step of hexose monophosphate shunt
glucose 6-phosphate dehydrogenase (G6PD); lifetime of RBC correlates with G6PD activity
27
conditions with excess methemoglobin
enzymatic deficiency in cytochrome b5 reductase or inherited hemoglobin M (stabilizes Fe3+)
28
what happens when someone with G6PD deficiency is given antimalarial drugs like primaquine
develop anemia
29
Heme formation step 1
glycine and succinyl CoA condense to form d-aminolevulinic acid (d-ALA)
30
requirement for d-ALA aynthase in step 1 of heme formation
requires participation of pyridoxal phosphate (rxn is an aa decarboxylation rxn…glycine decarboxylated)
31
Heme formation step 2
2 molecules of d-ALA condense to form pyrrole, porphobilinogen
32
Heme formation step 3
4 pyrrole rings condense to form linear chain and then a series of porphyrinogens
33
Heme formation step 4
porphyrinogens initially contain acetyl (A) and propionyl (P); acetyl groups decarboxylated to methyl groups
34
Heme formation step 5
1st 2 propionyl side chains decarboxylated and oxidized to vinyl groups, forming a protoporyrinogen
35
Heme formation step 6
methylene bridges are oxidized to form protopophyrin IX
36
Heme formation step 7 (final step)
Fe2+ incorporated into protoporphyrin IX; catalyzed by ferrochelatase (heme synthase)
37
what increases uptake of nonheme iron in digestive tract
vitamin C (ascorbic acid)
38
what form is iron absorbed/transported
absorbed as Fe2+, then converted by the ferroxidase ceruloplasmin to ferric state for transport
39
transferrin
iron plus apotransferrin; usually only 1/3 saturated with iron
40
iron binding capacity of blood
300 ug/dL (mostly due to transferrin)
41
morphology of vit B6 deficiency
microcytic, hypochromic RBCs; iron stores elevated
42
Pathology of lead poisoning
d-ALA and ferrochelatase are inactivated by lead; lack of hemoglobin and energy producation
43
Where is most iron stored
liver, spleen, and bone marrow
44
ferritin
apoferritin in complex with Fe3+; generally little in blood unless excess iron
45
hemosiderin
form of ferritin complexed with additional iron that cannot be readily mobilized; occurs when excess iron absorbed from diet
46
heme regulation
negative feedback; heme stimulated hemoglobin synthesis by stimulating protein globin synthesis
47
degredation of heme
degraded to bilirubin which is conjugated with glucuronic acid and excreted in bile
48
bilirubin processing in liver
reacts with UDP-glucuronate to form bilirubin monoglucuronide which is converted to diglucuronide and excreted into bile
49
iron lost per day in men
1 mg/dl; due to desquamation of skin, bile, feces, urine, and sweat
50
what should you suspect if male has iron-deficient anemia
GI tract bleeding (ulcers, colon cancer, etc)
51
RBC and spleen relationship
RBCs pass through spleen ~120 times per day taking ~30 s each time
52
iron deficiency vs vit B6 deficiency anemias
both have microcytic, hypochromatic, but iron level will differ
53
what results in a branched membrane cytoskeleton in RBCs
actin can bnd multiple spectrins
54
ankyrin
interacts with B-spectrin and integral membrane protein band 3; band 4.2 helps stabilize
55
band 4.1
anchors spectrin skeleton with membrane by binding integral membrane protein glycophorin C and actin complex
56
how do RBCs handle mechanical stress
spectrin network rearranges with some beoming uncoiled and extended while others compress
57
what is 2, 3-BPG made from
1, 3-biphosphoglycerate
58
buffer in tissues
CO2 converted into carbonic accid which dissociates into bicard and H+ ions
59
CO2 interaction with hemoglobin
forms carbamate adducts with the N-terminal amino groups of deoxyhemoglobin and stabilized deoxy form
60
population of hematopoitic stem cells
1 to 10 per 10^5 bone marrow cells
61
what secretes growth factors and regulates hematopoitic development
stromal cells (fibroblasts, endothelial cells, adipocytes, macrophages)
62
most hematopoietic growth factor receptors
cytokine receptor superfamily; JAK signal propagation
63
JAK phosphoylates what
STAT which dimerize and translocate to nucleus to affect gene transcription
64
SHP-1
tyrosine phosphatase necessary for proper dvlpmnt of myeloid and lymphoid lineages; dephosphorylates JAK2, inactivating it
65
Protein inhibitors of activated STAT (PIAS)
inactivated STAT
66
what occurs with a defective erythropoietin receptor
over production of RBCs since receptor can not be deactivated - sustained activation of JAK2 and STAT5; SHP-1 generally deactivates
67
fanconi anemia
bone marrow failure and increased susceptability to malignancy
68
RBC developmental precursors
1) stem cell to mixed myeloid progenitor cell (CFU-GEMM) 2) burst forming unit (BFU-E) 3) colony forming unit (CFU-E) 4) normoblast (first recognizable RBC) 5) reticulocyte
69
where do reticuloctes mature
in spleen where ribosomes and mRNA are lost
70
what type of anemia do folate and vit B12 defiencies cause
megaloblastic; nucleus extruded before cell divisions completed; fewer RBCs produced
71
What happens to unconjugated bilirubin in sickle cell
increases, causing gallstones
72
HbC
glu-lys replacement; promotes water loss by activating K+ transporter; homozygous have mild hemolytic anemia, heterozygous unaffected clinically
73
thalassemias
excess of one hemoglobin chain over another
74
HbF
lower affinity for 2, 3-BPG than adult hemoglobin aka greater affinity for O2
75
HbF composition
2 alpha and two gamma chains
76
HbA composition
2 alpha and two beta chains
77
point mutations in A-gamma and G-gamma promoters
have ameliorating (helpful) effect on sickle cell/b-thalassemia diseases due to increased gamma chain synthesis
78
embryonic megaloblast
1st embryonic RBC produced 15 days post fertilization; nucleus retained
79
when does erythropoiesis shift to liver
6 weeks, then also created in spleen
80
when does erythropoiesis shift to bone marrow
few weeks before birth; by 8-10 week post-birth, bone marrow is exclusive site of production
81
hemoglobin genes on chromosome 16
embryonic zeta gene, 2 copies alpha-gene
82
hemoglobin genes on chromosome 11
embryonic epsilon gene, 2 copies fetal beta gene, G-gamma, A-gamma, and two adult genes: detla and beta
83
order of hemoglobin genes on chromosomes
in order of expression during development
84
what controls switching of hemoglobin genes
transcription factor independent of environmental factors
85
hereditary spherocytosis cause
defect in ankyrin, B-spectrin, or band 3 are 75% cases; alpha-spectrin and band2 remainder
86
what immunizations should someone with splenectomy get
pneumococcus, meningococcus, Haemophilus influenzae type b

Biochem (3 decks)

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