MIDTERM Flashcards
1
Q
What monosaccharides make up lactose?
A
Glucose and galactose
2
Q
What monosaccharides make up sucrose?
A
Fructose and glucose
3
Q
What monosaccharides make up maltose?
A
Glucose (2)
4
Q
What enzyme breaks down lactose?
A
Lactase with the addition of H2O
5
Q
What are the two borders that must be crossed for monosaccharides to enter the bloodstream
A
Apical and basolateral border
6
Q
What transporter does glucose use to cross the apical border?
A
SGLT1 by active transport with 2NA+
7
Q
What transporter does galactose use to cross the apical border
A
SGLT1 by active transport with 2Na+
8
Q
What transporter does fructose use to cross the apical border
A
GLUT5 by facilitated diffusion
9
Q
What transporter do monosaccharides use to cross the basolateral border
A
GLUT2 by facilitated diffusion
10
Q
Is [NA+] greater inside or outside enterocytes?
A
Outside enterocytes
11
Q
What is primary lactase deficiency?
A
The irreversible loss of lactase expression after weaning; inherited
12
Q
What is secondary lactase deficiency
A
The reversible loss of lactase expression due to GI mucosal injury, damaging the brush border of small intestine; acquired and not inherited
13
Q
What are some major causes of mucosal injury for secondary lactase deficiency
A
Infections, allergies, and inflammation from other GI diseases (celiac disease, IBD, etc)
14
Q
What percentage of the world has lactose intolerance
A
70%
15
Q
What ethnic groups have low prevalence of lactose intolerance
A
Northern and central Europeans, North American caucasians
16
Q
What is lactase non-persistance caused by
A
Low lactase gene expression,
-low lactase protein expression,
-or low enzymatic activity of lactase protein
16
Q
What is lactase persistance
A
Group of individuals who retain their neonatal level of lactase activity into adulthood; mutants
17
Q
SNPs associated with lactase persistence are located in which gene
A
MCM6, a gene upstream and adjacent of lactase gene
18
Q
What SNPs are associated with lactase persistence in European and North American people
A
C>T in intron 13 of MCM6 or G>A in intron 9 of MCM6
19
Q
What SNPs are associated with lactase persistence in Asian and African people?
A
T>G C>G, or G>C in intron 13 of MCM6
20
Q
What are two transcription factors that activate LCT transcription
A
Cdx2 or HNF-1α
21
Q
What is the transcriptional repressor that inhibits Cd2x and HNF-1α function?
A
PDX-1
22
Q
What happens when PDX-1 is mutated (non-functional)?
A
LCT gene is expressed
23
Q
Where is the lactase enzyme expressed?
A
In the small intestine, not the colon
24
What is produced from bacterial fermentation of lactose in the colon?
Gases (H2, CO2, & CH4) and acids (lactic acid & acetic acid)
25
What are some lactose-fermenting bacteria that can be found in the colon?
Enteroacter sp., Citrobacter sp., Klebsiella sp., Escherichia coli, Serratia sp., and Streptococcus sp.
26
What are some non-lactose fermenting bacteria that can be found in the colon?
Salmonella sp. and Shingella sp.
27
What enzyme do lactose-fermenting bacteria express?
Beta galactosidase
28
What causes diarrhea in lactose intolerant people?
Water enters the colon to offset the acidic environment
29
What are some GIT-related symptoms of lactose intolerance?
Abdominal pain, bloating, flatulence, diarrhea, and nausea
30
What are some symptoms of lactose intolerance not related to GIT?
Headache, vertigo, memory impairment, lethargy, muscle & joint pain, cardiac arrhythmia, and mouth ulcers
31
What are some toxic metabolites that could cause symptoms in lactose intolerant people?
Acetaldehyde, acetoin, and ethanol
32
What are some different ways to diagnose lactose intolerance?
-jejunum biopsies,
-genotyping individuals,
-measuring blood glucose after lactose load,
-breath hydrogen test,
-exclusion diagnosis
33
What are the benefits of the breath hydrogen test?
Cost-effective, non-invasive, and reliable
34
What level of H2 in a BHT suggests lactose intolerance?
H2> 20ppm
35
What are some factors that affect the severity of lactose intolerance symptoms?
Level of remaining lactase activity, amount of lactose consumed at a time, GIT transit time, and composition of colon microbiota
36
Is it ideal to have a slow or fast transit time in the small intestine?
Slow; more opportunity for lactase activity to breakdown lactose
37
Is it ideal to have a slow or fast transit time in the colon?
Fast; minimizes lactose fermentation to reduce symptoms
38
What has more lactase activity: pasteurized or unpasteurized yogurt?
Unpasteurized yogurt
39
What are probiotics?
Live microbial supplements that benefit the host by improving intestinal microbial balance
40
What is pasteurization?
Process of heating food to destroy microbial activity; e.g. destroys beta-galactosidase activity
40
What are prebiotics?
Non-digestible food ingredients that promote the growth of beneficial intestinal bacteria
41
How are osteoporosis and osteopenia diagnosed?
Dual X-ray absorptiometry (DXA)
42
Where is calcium stored in the body?
99% in bones and teeth, 1% in blood and soft tissues
43
What hormone(s) are secreted in response to low blood calcium?
Parathyroid hormone (PTH) and calcitriol
44
What hormone(s) are secreted in response to high blood calcium?
Calcitonin
45
Where is calcitonin secreted from?
Thyroid parafollicular cells
46
What enzyme converts vitamin D3 to calcitrol in the liver?
25-hydroxylase and 1-a hydroxylase
47
What enzyme converts calcidiol to calcitriol in the kidneys?
1-a-hydroxylase
48
How does PTH increase blood calcium levels?
Stimulates calcitriol production by activating 1-a-hydroxylase, stimulates bone resorption, and maximizes tubular reabsorption of Ca in kidney
inhibits:
-Type 1 collagen formation
– Osteocalcin production in
osteoblasts
49
How does calcitriol increase blood calcium levels?
Stimulates bone resorption, increases Ca absorption in SI (TRPV6), and maximizes tubular reabsorption of Ca in kidney via increasin TRPV5 expression
50
How does calcitonin lower blood calcium levels?
Inhibits bone resorption, increases osteoblast activity, and suppresses tubular reabsorption of Ca in kidney
51
How does calcium cross the apical border of an enterocyte?
By passive diffusion (paracellular transport) or through TRPV6 calcium channels
52
How does calcium cross the basolateral border of an enterocyte?
Through calcium pumps (Ca+ out, H+ in) or sodium calcium exchangers (3 Na+ in, Ca+ out)
53
What is the function of calbindin?
Transports Ca to and from intracellular stores in the mitochondria and ER to maintain Ca levels in enterocytes and blood
54
What condition is characterized by sustained secretion of PTH when Ca levels are normal?
Familial hypercalcemic hypocalciuria (FHH)
55
What is the type of bone found in the outer layer of bones and the bulk of the interior of long bones?
Cortical bone
56
What is the type of bone found in the interior of bones?
Trabecular bone (spongy bone)
57
What are the four types of bone cells?
Osteogenic cells, osteoblasts, osteocytes, and osteoclasts
58
What type of stem cell do pre-osteoblasts develop from?
Mesenchymal stem cells (from osteogenic cells)
59
What growth factor allows pre-osteoblasts to differentiate into osteoblasts?
Runx2
60
What type of stem cell do pre-osteoclasts develop from?
Hematopoietic stem cells (from osteogenic cells)
61
What stimulates the differentiation of pre-osteoclasts into osteoclasts?
Binding of RANK-L to RANK
62
What is the major crystalline salt of the bone?
Hydroxyapatite
63
What is the organic matrix of bones formed of?
90-95% type 1 collagen fibers and 5-10% ground substance (EC fluid + proteoglycans)
64
How are chondroitin sulfate and hyaluronic acid involved in bone composition?
They are proteoglycans that form part of the ground substance of the bone's organic matrix
65
What do osteoblasts secrete (list 5)?
Type 1 collagen, osteocalcin, osteonectin, RANK-L, and OPG
66
What does osteocalcin bind to?
Calcium and hydroxyapatite
66
What does osteonectin bind to?
Collagen fibers and hydroxyapatite
67
How do BMP, TGFβ, IGF, FGF, PDGF, and VEGF affect bone formation?
They stimulate osteoblast activity
68
What is osteoprotegerin (OPG)?
Binds to RANK-L to inhibit RANK/RANK-L osteoclast maturation
69
What stimulates OPG secretion?
Estrogen, IL-4, and TGFβ
70
What stimulates RANK-L secretion?
Calcitriol, PTH, TNFα, IL-6, and PGE2
71
How does estrogen affect bone turnover?
Stimulates bone formation
72
What is M-CSF and what does it do?
Cytokine that stimulates expression of RANK on osteoclasts; required for OC maturation and activity
73
What do osteoclasts secrete for bone resorption?
Proteolytic enzymes (cathespin K) to digest organic matrix; citric acid to dissolve hydroxyapatite; TRAP proteins to allow OC to move along bone surface
74
How is aromatase involved in bone formation?
Aromatase (increased in obesity) increases estrogen production
75
How does obesity adversely affect bone status?
Inflammatory cytokines stimulate osteoclast activity, vitamin D levels are reduced, and serum PTH is high
76
What are some examples of dietary bioactives that reduce bone resorption?
Plant polyphenols (resveratrol & catechin); soy isoflavones (genistein & diadzein); n-3 PUFAs
77
What are some mechanisms in which plant polyphenols reduce bone resorption?
Suppresses NFkB, inhibits RANK-L secretion, stimulates OPG secretion, increases Runx2 expression, inhibits osteoclastogenesis, etc.
78
What are some mechanisms in which soy isoflavones reduce bone resorption?
Stimulates 1-hydroxylase expression, increases OPG & osteocalcin secretion, reduces RANK-L secretion, induces osteoclast apoptosis, etc.
79
What are some mechanisms in which n-6 PUFAs affect bone turnover?
n-6 PUFAs produce the inflammatory eicosanoid PGE2, which: decreases OPG secretion, increases RANK-L secretion, and inhibits osteoclast apoptosis
80
What are some mechanisms in which n-3 PUFAs affect bone turnover?
Decreases NFkB & STAT3 activation, decreases RANK-L & M-CSF secretion, etc.
81
What is metabolic syndrome?
Cluster of medical disorders that increase the risk for CVD and diabetes
82
For a diagnosis of metabolic syndrome, a person would have at least one of the following conditions:
Type 2 diabetes, impaired glucose tolerance, impaired fasting glucose, and insulin resistance (along with 2 of: HBP, dyslipidemia, obesity, microalbuminuria)
83
How could calcium (combined with vitamin D) cause weight loss?
Increases fecal fat excretion, promotes fat oxidation in adipose tissue, and suppresses apetite
83
What are some typical symptoms of celiac disease?
Abdominal distension, anorexia, chronic diarrhea, and failure to thrive
83
What are the three types of apical junctional complexes in enterocytes?
Tight junctions, adherens junctions, and gap junctions
84
What is the function of tight junctions?
Seals enterocytes together to prevent leakage between them
85
What proteins form the structure of tight junctions? What are they anchored to?
Claudins, JAMS, and occludins; they are anchored to zona occludins (ZO) which bind to the actin cytoskeleton
86
What is the function of adherens junctions?
Joins an actin bundle in one cell to a similar bundle in a neighboring cell
87
Where are M cells found?
Epithelial barrier covering Peyer's patches
88
What are Peyer's patches?
Localized follicles of immune cells (APCs, B cells, T cells) found in the small intestine
89
What happens to whole proteins that are absorbed by enterocytes?
90% are degraded by lysosomes, 10% are released as intact proteins
90
What happens to whole proteins that are absorbed by M cells?
50% are degraded and processed into antigens, 50% are released as intact proteins
91
What are the three types of APCs?
Dendritic cells, macrophages, B cells
92
What type of T cells do MHC class I molecules bind to?
CD8+ T cells
93
What type of T cells do MHC class II molecules bind to?
CD4+ T cells
94
What are the two signals required to activate naive T cells?
Signal 1: TCR + antigen + MHC class I
Signal 2: CD28 (stimulatory) or CTLA4 (inhibitory) + CD80/CD86
95
What is the second stimulatory signal needed for T cell activation?
Binding of CD28 (on T cell) to CD80/CD86 (on APC)
96
Combination of antigen and MHC molecule recognized by T cell:
They differentiate into a T helper subset and proliferate to form many clones
97
What T cell subset are T cells that have encountered gluten antigen?
TH1 subset
98
What transcription factor directs naive T cells to develop into TH1 cells?
Tbet
99
What cytokine is produced from activated TH1 cells?
IFNy
100
What are the four gluten proteins?
Gliadins, glutenins, hordeins, and secalins
101
What gluten protein is found in barley?
Hordeins
102
What gluten protein is found in rye?
Secalins
103
How does the high proline content of prolamins affect their digestion?
High proline content makes prolamins resistant to digestion
104
How does the high glutamine content of prolamins play a role in CD?
High glutamine content makes prolamins favourable to deamidation reactions by TTG
105
What forms of MHC class II receptors are found in people with celiac disease?
HLA-DQ2 and HLA-DQ8 (possibly HLA-DQ7)
106
What two factors influence the high binding affinity of HLA-DQ2 or DQ8 and gluten?
High glutamine content of gluten and deamidation of gluten by TTG
107
What enzyme deamidates glutamine residues in gluten?
Tissue transglutaminase (TTG)
108
What positions of the antigen-binding groove in HLA-DQ2 have a high affinity for negatively charged residues?
4, 6, and 7
109
What positions of the antigen-binding groove in HLA-DQ8 have a high affinity for negatively charged residues?
1 and 9
110
Through what mechanisms does large gluten peptides leak across the epithelial barrier?
APC-mediated luminal capture of gluten peptides, M cell transcytosis, or enterocyte luminal uptake of antigens and passing to APC
111
How does IFNy cause tissue damage in CD?
Triggers MMP activation and activates APCs, causing them to secrete TNFa
111
What cytokine triggers MMP activation in the CD immune response?
IFNy
112
How does IL-21 cause tissue damage in CD?
Promotes TH1 cell response, activates IELs, and amplifies effects of IL-15
113
How does IL-15 cause tissue damage in CD?
Induces epithelial cells to express MIC proteins (MIC-A), leading to IEL activation
114
How do activated IELs mediate enterocyte apoptosis?
Binding of FasLigand to Fas and releasing granules containing perforin and granzymes
115
What ligand binds to receptor NKG2D on the surface of IELs, leading to IEL activation?
MIC-A
116
What are IELs?
CD8+ cells and NK cells
116
What is IL-21 produced by?
TH1 clones
117
What is IL-15 produced by?
APCs
118
What cytokine activates B cells in the CD immune response?
IL-21
119
What types of antibodies are produced in the CD immune response?
Anti-gluten, anti-TTG, anti-collagen, anti-actin, and anti-endomysium
120
What binds to the receptor CD71 on the apical surface of enterocytes?
Anti-gluten antibody + gluten complex
121
What happens when TTG is bound to an anti-TTG antibody?
TTG cannot promote ECM assembly, therefore perpetuating tissue damage
122
What binds to the CXCR3 receptor on enterocytes in CD?
Zonulin
123
What is the role of zonulin in celiac disease?
Increases intestinal epithelium permeability by loosing tight junctions between cells
124
How does IFNy stimulate TTG activation?
By stimulating the protein cofactor Thioredoxin-1
125
How should celiac diease be diagnosed?
Serology testing of IgG anti-gliadin and IgA anti-TTG, or biopsies from duodenum
126
What are the extra-intestinal symptoms of atypical celiac disease?
Dermititis herpetiformis, anemia, osteoporosis, arthritis, infertility, etc.
127
What are the types of cancer that are associated with celiac disease?
Gastrointestinal cancer and lymphoma
128
What is the best treatment for celiac disease?
Gluten free diet
129
Function of perforin
pokes holes in the epithelial cell
plasma membrane
130
Function of granzymes
enter the epithelial cell activating
caspase-3 and trigger epithelial
cell apoptosis
131
RhoA
plays a central role in regulating cell shape and polarity through its effects on actin polymerization, cell adhesion and structure of actin cytoskeleton
132
Cdc42
regulates cell polarity and cell morphology. Supports the formation of actin filaments and the integrity of the actin cytoskeleton
133
Reduced mucous secretion
Loss of protective mucous barrier
134
Absorption
Small intestine
135
Reabsorption
Kidney
136
Resorption
Bone
137
Both RhoA and Cdc42 play a key role in
Cell migration, (movement of epi cells to fill a gap or breach in the epi barier)
138
Antigen definition
molecules capable of stimulating an immune response
139
uptake
phagocytose antigen
140
process
cleave large antigen into smaller sequene of amino acids
