Week 5 Flashcards
1
Q
4 Primary Ethical principles in medicine
A
1) Beneficience
2) Automony
3) Justice
4) Nonmalficence
2
Q
What is meant by Beneficence?
A
Acting for the benefit of OTHERS
3
Q
What is meant by Autonomy?
A
Respecting individual has the right to choose/refuse
Ability to make their own choices for their care
4
Q
What is meant by Justice?
A
Fairness in terms of access and distribution of resources
5
Q
What is meant by Non-maleficence?
A
DO NO HARM
Cause no unnecessary risks or needless harm to patients
6
Q
Why is it important to develop a rapport with patients?
A
Relationship will determine QUALITY of info received and completeness of information
7
Q
What are tenets of the Patient-centered clinical approach
A
Explore patient disease/illness experience
Understanding of WHOLE person not just the disease
Enhancing Doc/Patient relationship
8
Q
Importance of confidentiality in healthcare?
A
Respect for patients and their privacy - don’t discuss them in public
Allows patients to discuss more sensitive topics with provider
Fosters sense of care-seeking - more willing to seek care
Prevent harm from coming to patients - lose jobs, etc.
9
Q
Define a boundary in terms of patient-doctor relationship
A
Edge of appropriate, professional and clinical behavior
10
Q
Why are boundaries a fine line?
A
Deciding what is considered exploitive or non-exploitive
11
Q
What might be some instanced of boundary issues?
A
Treating family
Accepting gifts from patients
Provider ideology
Any sort of sexual conduct
Touch - necessary but ONLY WHEN necessary
Social gatherings - avoid on social media!
12
Q
Referrals:
When to use?
When NOT to use?
A
1) ONLY if clear benefit to patient - if outside scope of practice of provider
2) NEVER to avoid death at facility (for statistical purposes)
3) If someone promises you charges/fee splitting - NOPE!
13
Q
Ethical issues in patients refusing treatments?
A
When in doubt on treating a patient - autonomy wins out
14
Q
Consent v. Assent
A
Consent: anyone over legal age of consent (>18yo)
Assent: more for minor to signal willingness to participate
15
Q
Informed consent
A
Allowing patient to know all risks/benefits involved with refusal of care
Patient MUST posses proper decision making capacity in order to UNDERSTAND consequences
Consent must be obtained without coercion or manipulation
16
Q
Define: population
A
Group of individuals who share common characteristic
17
Q
Define: Sampling
A
Process of selecting subset group from a larger population for purpose of study
18
Q
Define: sampling frame
A
List of individuals that are eligible for selection in research study
19
Q
Pros to sampling frame
A
More confidence in generalized results of study as applied to a larger population
20
Q
Sampling external validity
A
How well findings can be applied to other situations
21
Q
Sampling Internal Validity
A
whether design, conduct, analysis of the study ITSELF answers the questions without bias
22
Q
Subtypes of Sampling Categories:
1)
2)
A
1) Probability/Random Sampling
2) Non-probability/Nonrandom Sampling
23
Q
Describe simple random sampling
A
Selection of individuals from population using random number generator
24
Q
Describe Stratified random sampling
A
Divides population into SUBGROUPS based on certain characteristics
Random selection done of all subgroups
25
Describe Cluster sampling
Divides population into clusters (based on geography)
Randomly will select clusters to sample from
26
Describe Systematic sampling
Selection of every "n"th member of population at a randomized starting point
27
Describe Convenience sampling
Selection of individuals with easy access/willingness to participate in study
28
Describe Snowball sampling
Selection of few individuals from population
Those few individuals refer others who fit criteria as wel
29
Describe Purposive sampling
Selection of individuals who meet specific criteria FOR the study
30
Describe Quota sampling
Researcher has liberty to select sample based on THEIR strata
Two people cannot exist under 2 different conditions
31
Describe Self-selection
Specific type of people are more likely to participate in research study
32
Describe Non-response
Certain type of people more likely to refuse to participate in study
33
Define inclusion criteria:
Characteristics/features permitting someone to be eligible participant in study
34
Define exclusion criteria
Characteristics/features disqualifying someone from participation in research study
35
Principles of inclusion/exclusion criteria:
1)
2)
3)
4)
1) Relevance
2) Feasibility
3) Exclusivity
4) Representative
36
Importance for inclusion/exclusion criteria:
1)
2)
3)
4)
1) Enhance study validity
2) Reduce participation risk
3) Increase generalizability = include representative population
4) Facilitate feasibility
37
Define sampling error
Statistical error when analyst does NOT select sample representative or entire population of date
38
Types of sampling errors:
1)
2)
3)
4)
1) Population specific error - wrong population included for study
2) Sample frame error/coverage error - Wrong list of people to deal with
3) Selection error - Chose wrong sent of respondents
4) Non-response error - people didn't show up or respond
39
Methods to deal with sampling errors
1) Choosing correct sample for study
2) Increase the sampling size
3) Ensure baseline characteristics of participants
4) Weighted sampling of participants
40
Non-sampling errors -
*No matter what they cannot be fixed by increasing sampling size.*
1) Systematic error - Selection bias
2) Chance
3) Confounding
41
Conditions of Informed Consent
FULL disclosure of information -
1) Procedures and purpose of study
2) Risk vs Benefits of study
3) Alternatives to research pool
4) Conditions of participation
42
What is meant by conditions of participation in informed consent?
Participants have right to refuse or leave study at any time without penalty
Contact info for questions concerning study, participants rights WITHIN study
43
Persons with limited decision making capacity
LEGALLY authorize someone to make decisions
Approach someone with intermittent incapacitation when lucid
44
Those considered part of the vulnerable population
Children
Pregnant women
Prisoners
45
Define coercion
Threats (either explicit or implicit)
46
Define undue influence
Excessive compensation
47
Historical Highpoints arising in medical research
Nuremburg Trials
Thalidomide
Tuskegee Syphilis study
48
Describe Primary Research
Research that has been collected BY researcher
49
Describe Applied Research
Use of either animal testing or cell cultures to test
50
Describe Theoretical Research
Usually used in test development
51
Describe Descriptive Research
Used in prognosis determination of certain diseases
52
Describe Interventional Research
Something is being tested for
Drug trials
53
Describe Epidemiological research
Research done at a much larger scale
Happening within a population
54
Describe Analytical Observational Studies
Cohort Studies:
Observation of people over time
Association of risk factors and outcomes
55
Describe Analytical Observational Studies
Case Control Studies
Comparison of one group to control group
Association of risk factors vs rare outcomes
56
Describe Analytical Observational Studies
Cross-sectional Studies
Take a group of people, gather average amount of information
Prevalence of diease!
57
Describe Analytical Interventional Studies (with RCT's)
Doing research at a larger level
Exploration of cause/effect of something
58
Define Secondary Research
Using data collected via other people for own research purposes
59
Describe Reviews
Cochrane Library
Used to find reviews of medical literature for average layperson
60
Describe Meta-analyses
Statistical combo of various studies wo come up with overall result for studies in certain area
61
Describe Databases
Collection of data to be used for research purposes
62
Describe Scientific Method
Ask
Hypothesis
Gather
Analyze
Conclude
Recommend
63
Goals of Descriptive Research
Summation of characteristics of group
64
Goals Predictive Research
Forecast outcomes of something
65
Goals of Explanatory/Causality Inference Research
Establish causal link/mechanism
66
Types of Info from Research
Descriptive
Describe X and Y and how they relate to ones another
67
Types of Info from Research
Correlational
Is there a relationship between X and Y
68
Types of Info from Research
Experimental
Change in X will affect Y in what way?
69
Types of Info from Research
Literature Review
Look at all studies and find which conclusions work best for X and Y
70
Variables seen in research
Types of responses
Different levels observed
71
Describe Hypothesis testing
Formulation hypothesis based on question being asked
72
Null hypothesis
No difference in relationship
73
Alternate hypothesis
There is some difference
74
Two types of Alternate Hypotheses
One-sided: Directional relationship
Two Sided: Non directional; some impact occurs
75
Types of Errors
Type I
Type II
76
Explain Type I error
Rejection of the null hypothesis when it should have been accepted
Alpha error
Relationship demonstrated
77
Explain Type II Error
Failure to reject the null hypothesis - should have and didn't
Beta error
No relationship demonstrated
78
Describe Case Study
Advantages?
Disadvantages?
Study of one patient/case
Advantage: Observe someone with unusual circumstances
Disadvantage:
79
Define power
Probability of NOT making a Type II error
Probability of finding a difference between groups IF one exists
80
Describe Observation
Advantages?
Disadvantages?
Real-life observations of patients/case
Advantage: Real-life, real-time
Disadvantage:
81
Describe Surveys
Advantages?
Disadvantages?
Written/oral questionnaires
Advantage: Quick, cheap, familiar
Disadvantage:
82
Describe Archival research
Advantages?
Disadvantages?
Using existing records/databases
Advantage: cheap, data exists already
Disadvantage: Data quality not great
83
Describe Interviews
Advantages?
Disadvantages?
Interview of someone
Advantage: In-depth understanding/explanation of phenomenon
Disadvantage:
84
Describe Experiments
Advantages?
Disadvantages?
Cause and effect
Advantage: Causality
Disadvantage: Ethical considerations
85
Calculation of power of study
1- beta
86
Ways/means to increase power in study
Increase sample size
Have marked differences between groups
Lower SD
87
Define p-value
How much of observed data disagrees with null hypothesis
Greater the difference = lower the p-value
88
Low p-value
Reject null hypothesis
89
High p-value
Failure to reject the null hypothesis
90
Alpha level
Probability of making Type I error
If less than 5% = statistically significant
91
Bias
Systematic error in collection/interpretation of data found in study design
92
Hierarchy of Evidence Pyramid
93
Stages of Mitotic Cell Division and What Occurs There:
G1
All Cellular contents (except DNA) replicate
Preparation of Replication proteins ramps up
94
Stages of Mitotic Cell Division and What Occurs There:
S
DNA replication occurs
95
Stages of Mitotic Cell Division and What Occurs There:
G2
More of a checkpoint to ensure everything is good before mitosis
Production of proteins to aid mitosis occurs here
96
Stages of Mitotic Cell Division and What Occurs There:
Prophase
Chromosomes condense
Nuclear envelope begins to disappear
Mitotic spindle assembles
97
Stages of Mitotic Cell Division and What Occurs There:
Prometaphase
Nuclear envelope is gone completely
Chromosomes attach to microtubules via kinetochores
98
Stages of Mitotic Cell Division and What Occurs There:
Metaphase
Chromosomes align along equator
Sister chromatids attached to opposite poles of mitotic spindle
99
Stages of Mitotic Cell Division and What Occurs There:
Anaphase
Chromatids pulled apart
Chromatids are slowly pulled to opposite poles of cell
100
Stages of Mitotic Cell Division and What Occurs There:
Telophase
Chromosomes arrive at opposite pole
Nuclear envelope begins to reappear
Contractile ring of myosin/actin begins to form and contract
101
Stages of Mitotic Cell Division and What Occurs There:
Cytokinesis
Contractile ring continues to contract until 2 new cells formed
102
Mitosos:
Produce 2 ID cells
Each cell has 46 chromosomes (2n)
1 S phase, 1 division phase
103
Meiosis
Produce 4 different cells
Each cell has 23 chromosomes within it
1 S phase, 2 divisions
104
DNA Content through different stages of Mitosis
105
DNA Content through different stages of Meiosis I
106
DNA Content through different stages of Meiosis II
107
Role of Actin Microfilaments in Mitosis
Actin with myosin form contractile ring
108
Role of Intermediate Filaments in Mitosis
Formation of nuclear lamina
Will dissolve due to phosphorylation of proteins
109
Role of Microtubules in Mitosis
Formation of mitotic spindle
Attach to kinetochores
110
Cohesions
Proteins that regulate separation of sister chromatids during cell division
111
Cohesions broken down via _________________ during what phase?
Separase enzyme
Anaphase
112
Condensins
Large proteins that play role in chromosomal assembly and segregation during mitosis/meiosis
113
If functionality of cohesiens/separase occurs - what is result?
Non-disjuction of the chromatids
114
Results of non-disjunction?
Trisomies or monosomies
115
When can non-disjunction occur
Anytime during mitosis, meiosis I or II
116
Mosaicism
Present of cells with differing contents within ONE person
117
Taxol and why Oncologists love it?
Halt spindle checkpoint between Metaphase and Anaphase
Causes minor alteration of spindle microtubules to engage apoptosis
Prevents out of control cancer cells from replicating - also prevents high traffic area cells from replicating as well.
118
Contact Inhibition
Where one cell meets up with another while replicating and says "Sorry neighbor, not trying to intrude on your space" and stops building their cell empire.
119
Possible origins of mitochondria
Aerobic cell that was engulfed by anaerobic cell
120
Special features of mitochondria
Own DNA and ribosomes
No need to send or receive vesicles - manufactures own items for self (can receive proteins from nucleus)
121
Structure of mitochondria
Membrane enclosed
0.5-1.0 micrometers in diameter
10 micrometers in length
Form ATP in ETC
Seen in greater numbers in active cells in body
122
Outer membrane function of Mitochondria
Contains Porins = form aqueous channels in membrane
Molecules up to 5000 daltons allowed to pass through
Needed for release of newly synthesized ATP
123
Inner membrane function of Mitochondria
- Form folds known as cristae
- Cristae used to increase surface area of inner membrane
- Impermeably to ions - only allow molecules needed for ETC to pass thru
124
Transmembrane proteins of the Inner membrane of Mitochondria
Cytochrome C oxidase (Complex IV)
ATP Synthase
ADP/ATP Carriers (antiporters)
125
Mitochondrial Matrix function of Mitochondria
Mix of enzymes for various metabolic functions
Contains matrix granules
Contains several copies of mtDNA, tRNA and ribosomes
126
Function of Matrix granules
Storage of extra Ca2+
127
Metabolic processes that involve mitochondrial enzymes
1) Oxidation of pyruvate
2) Oxidation of FA's
3) TCA Cycle
128
Structure of mtDNA (Mitochondrial DNA)
Circular dsDNA
NOT packaged by histones
129
mtDNA codes for how many genes?
37
13 proteins, 22 tRNA, 2 rRNA
130
Function of Mitochondrial Protein Targeting Sequence
Proteins tagged to be transported to mitochondria
131
Target sequence for tagging proteins for mitochondria
5-10 AA sequence
132
Where are these sequences translated at
Free Ribosomes within cytoplasm
133
What allows for transport of protein into matrix?
Mitochondrial Matrix Targeting Sequence
134
Transmembrane proteins involved with transportation
TOM (Translocase protein of Outer Matrix)
TIM (Translocase protein of Inner Matrix)
135
Inheritance of mitochondrial DNA
Maternal ONLY
136
Why only maternal inheritance of mtDNA?
Paternal mitochondria is tagged with ubiquitin to be degraded by proteosomes
137
What is Oxidative Phosphorylation
Breakdown of food molecules into ATP using O2 as final acceptor molecule
138
Why is Carbon Monoxide so dangerous for OxPhos?
Will bind to heme moiety in Complex IV and inhibit respiration and ATP formation
139
What other areas does Mitochondria participate in?
Apoptosis
Steroidogenesis (seen as tubular structures called tubular cristae)
Thermogenesis
140
Structure of Peroxisomes
Spherical organelles
Enclosed via SINGLE membrane
Contain NO DNA
Can contain up to 37 different enzymes (peroxins)
141
Peroxin proteins are encoded by?
PEX genes
142
How to peroxisomes appear on TEM
Electron dense area
143
Formation of peroxisomes:
2 ways
Fission
De Novo synthesis
144
Describe Fission formation of peroxisomes
Pre-existing peroxisome divided in 2
Slower process for formation
145
Describe de novo synthesis of peroxisomes
Pre-peroxisome vesicle buds off sER
Will contain specific proteins that will import PTS-containing proteins
Become functional peroxisome
146
Functions of Peroxisomes:
Breakdown of VLCFA's
Done via beta-oxidation of FA's
VLCFA undergo initial oxidation in peroxisomes
Oxidation in peroxisomes NOT COUPLED to ATP production
Yields H2O2
147
Functions of Peroxisomes:
Breakdown of H2O2
H2O2 accumulates in cell
H2O2 is harmful ROS
Catalase will breakdown H2O2 into H2O and O2
148
Functions of Peroxisomes:
Formation of Bile Acids
Formed in LIVER ONLY
Formed from cholesterol from sER
H2O2 used to convert cholesterol into bile acids
149
Function of Bile Acids
Emulsify gastric contents into substances that can be absorbed
150
Functions of Peroxisomes:
Detoxification
Rid body of toxins
Number of peroxisomes in liver/kidneys is usually high because of this
151
Functions of Peroxisomes:
Formation of myelin
Myelin - lipid/protein sheath surrounding nerve
Seen in CNS/PNS
Formation of special phopholipid = plasmologen
152
Zellwegers Syndrome
Affects plasmologen synthesis in peroxisomes
Mutation of receptors of Peroxisomal Targeting Signal
Patients cannot import proteins into peroxisomes
153
Adrenoleukodystrophy (ADL)
Mutation in member of ATP-binding cassette transporter family of proteins (ABCD1)
Breakdown/loss of myelin; progressive loss of function of adrenal glands
Inability of peroxisomes to import VLCFA's inside - VLCFA's will accumulate in serum
154
Concerning metabolism, what occurs during hypoxia?
Glycolysis increases
TCA/OxPhos decreased
Lactic Acid begins to form and accumulate
Increased concentrations of NADH
155
What is hypoxia-inducible factor?
Under hypoxic conditions, will begin to transcribe proteins needed to increase O2 flow to areas under hypoxic stress
156
Under normal conditions - what is function of hypoxic inducible factor?
Usually Hydroxylated via HIF-prolyl hydroxylase - not active
Tags it with ubiquitin for degradation in proteosome
157
Enzyme preventing activation of HIF?
HIF-prolyl hydroxylase
158
Mutations in mtDNA - classified as?
1) Homoplasmic - seen in all mtDNA
2) Heteroplasmic - seen in some mtDNA, not in others
159
Effects of Hypoxia:
1)
2)
3)
4)
5)
6)
1) Loss of ATP generation
2) Failure of ion pumps - build up of oxidative stress
3) Glycolysis ramped up
4) Formation and accumulation of lactic acid - tissues become acidic
5) Membranes begin to leak
6) Lysosomal enzymes become active
160
Type of free radicals
Superoxide
Hydrogen Peroxide
Hydroxyl radical
161
Describe superoxide radical
Reactive but not the worst
Cannot cross membrane due to charge (anion)
Converted to H2O2 by Superoxide dismutase
162
Enzyme that denatures superoxide radicals
Superoxide dismutase
163
Describe Hydrogen peroxide radical
Conversion of Superoxide into H2O2
Can convert into a hydroxyl radical
164
Enzyme that denatures H2O2
Catalase
165
Describe Hydroxyl radical
Can be catalyzed in blood by free iron within blood
166
Enzyme that denatures hydroxyl radical
Glutathione peroxidase
167
Other ways for ROS to collect extra electrons?
Stray electrons from ETC (Complex I, II, III)
Ionizing radation
Flavoproteins (Fava beans)
NADPH oxidase/xanthine oxidase
168
What is the Haber-Weiss Rxn?
Equation showing how ferrous/ferric iron can catalyze formation of hydroxyl radial from H2O2
169
Examples of non radical oxidants
Ozone
Singlet Oxygen
Hypochlorus acid
Peroxynitrite
170
Examples of Free Radical Oxidants
Peroxyl
Alkoxyl
Hydroperoxyl
NO
171
Effects of ROS on Proteins:
Oxidize Cysteine and Methionine
Disturb iron-sulfur centers of cysteine and methionine
Will break peptide bonds between proteins
172
Effects of ROS on DNA:
Oxidation of nucleotide bases
Most common - 8-oxoguanine (removed via BER)
Will form double strand breaks in DNA
173
Effects of ROS on Lipids:
Oxidation of POLYUNSATURATED FA's
Usually caused by free radical propagation
174
Do ROS oxidize saturated FA's or monounsaturated FA's
NOPE.
175
Steps for Free radical propagation in FA's
1) Peroxide reacts with polyunsaturated lipid = forms free radical
2) Free radical interacts with O2 = forms lipid peroxyl radical
3) Lipid peroxyl radical moves on to another molecule to do it's thing = leaves behind peroxide lipid
176
What vitamin breaks free radical propagation of lipids?
Vit E
177
Structure/Function of superoxide dismutase:
Will convert superoxide radical into H2O2
Is a manganese containing enzyme within the mitochondria
Contains zinc-copper if enzyme is present in cytoplasm
178
Structure/Function of Catalase:
Destroys H2O2
Is a heme-containing enzyme that is widespread throughout all body fluids
(Greatest concentration found in peroxisomes)
179
Structure/Function of glutathione peroxidase:
Destroys hydroxyl radical and hydrogen peroxide
Is present in cytoplasm and in mitochondria
180
Reduced glutathione
G-SH
181
Oxidized Glutathione
GS-SH
182
What does glutathione do?
Maintain redox state of cytoplasm
183
Where is the reducing environment for glutathione?
Cytoplasm
184
How is G-SH regenerated?
From GS-SH using NADPH reducing equivalents
185
Where do NADPH reducing equivalents come from?
HMP Shunt
186
Role of dietary antioxidants and ROS:
Roam around and scavenge free radicals
Will end up forming STABLE free radical that can do no other damage to cells
It will destroy other free radicals in the process
187
Examples of Water Soluble antioxidants
Vit C
Uric acid
Phytochemicals
188
Examples of Fat-soluble antioxidants
Vit E
Vit A
Reduced CoQ
189
How does NADPH oxidase function in phagocytosis?
It is a plasma membrane bound enzyme specifically for making ROS
Used to kill phagocytosed bacteria in cells
190
NRF2-KEAP1 system function?
Protection against oxidative stress
191
Under oxidative stress, how does NRF2-KEAP1 function?
NRF: is a transcription factor; will stimulate transcription of antioxidant genes
KEAP1: Will bind to antioxidant response element on DNA
192
Under normal conditions, how does NRF2-KEAP1 function:
NRF2 is kept within cytoplasm as the master regulator of cell redox state
NRF2 inevitably sent to proteosome via KEAP1 (senses oxidation within cells)
193
Primary storage site of glycogen
Liver and Muscle cells
194
Composition of glycogen:
alpha 1,4 chains of glucose
alpha 1.6 branches of glucose
195
Storage of glycogen in liver:
Function of?
Maintain blood glucose levels during times of fasting/between meals
196
How long does glycogen reserve in liver last for?
Approx 12 hrs
197
Muscle glycogen:
Function of?
Direct source of glucose for muscles
198
What enzyme do muscles lack for conversion of glucose?
Glucose-6-Phosphate
199
When released from muscle, where does glucose go?
Remains in muscle
200
What does glucagon stimulate?
Breakdown of glycolysis
201
What does epinephrine signal in muscle cells?
Glycogen breakdown in muscle cells
202
What is glycogen broken down into in muscle?
Glucose-1-phosphate
203
What it glycogen broken down into in the liver?
Immediate glucose to be released and utilized by bloodstream
204
Where does gluconeogenesis insert itself in glycolysis?
Glucose-6-Phosphate
205
Excess glucose in blood triggers?
Insulin and GLUT4
206
As glucose concentration increases, what will happen to hexokinase velocity?
Will increase sharply and become saturated in tissues OTHER than the liver
207
As glucose concentration increases, what will happen to Glucokinase velocity?
Will increase steadily over time in the liver
208
What are GLUT4 proteins
Transport proteins enabling glucose to enter muscle and adipose cells
209
What enzyme interconverts glucose-1-phosphate into Glucose-6-phosphate?
Phosphoglucomutase
210
What is glycogenin?
Protein core of glycogen that is surrounded by 10,000 molecules of glucose
211
What enzyme adds glucose units to non-reducing ends of glycogenin?
Glycogen synthase
212
What is the function of glycogenin?
Primer upon which other glucose molecules can attach to.
213
How does glycogenin add glucose molecules to itself?
Will autocatalyze glucose molecules to self til certain point.
214
What is the primary enzyme that allows glycogenin to add UDP-glucose to itself?
Glucosyltransferase
215
Once sufficient moieties added to glycogenin, what enzyme takes over additon of UDP-glucose?
Glycogen synthase
216
How often to brand points appear in glycogen molecules?
Every 8-10 glucose residues
217
What enzyme transfers glucose molecules from main chain (1,4) to branch chain (1,6)?
Glycosyl 4:6 transferase
(Branching enzyme)
218
What enzymes break down glycogen?
Alpha-amylase either in pancreas and salivary glands
219
Why do glycogen synthesis and breakdown have different enzymes?
Allow for activation of ONE pathway at a time (one active, other inhibited)
220
Breakdown of glycogen in liver:
Reason?
Regulate blood sugar
221
Breakdown of glycogen in muscles:
Reason?
Provide substrate for ATP production
222
Primary enzyme responsible for glycogen breakdown?
Glycogen phosphorylase
223
How does Glycogen phosphorylase function?
Start with non-reducing ends and cleave alpha (1,4) bonds
Will cease when 4 glucose moieties left
224
How are terminal 3 glucose molecules removed from branches?
Debranching enzyme
4:4 transferase and alpha (1,6) glucosidase
225
Function of alpha 1,6 glucosidase?
Remove remaining single glucose at branching point
226
Glycogen synthase stimulated via?
Increased G6P levels
227
Glycogen phosphorylase inhibited by?
Increased energy levels (ATP)
228
Glycogen phosphorylase activated by?
Activated by low-energy signals
Increased Ca2+ and AMP
229
Signals activate glycogenolysis in liver and muscle?
Liver: Glucagon
Muscle: Epinephrine
230
Mechanism of action of glycogenolysis?
Phosphorylating and activation of phosphoylase (via cAMP)
231
Increased Ca2+ leads to in muscle?
Activation of phosphorylase kinase
Triggers activation of glycogen phosphorylase
232
Increased AMP in muscle?
Can activate glycogen phosphorylase B
233
Glycogen synthase:
Activated by?
Inhibited by?
Activated by: Insulin
Inhibited by: Glucagon/epinephrine via cAMP/PKA pathway
234
Activation of glycogen synthase via:
1)
2)
1) Activation of phosphatase-1 (dephosphorylates glycogen synthase)
2) Activation of PKB (phosphorylates GSK-3; inactivates)
235
Example of dietary lipids
Triglycerides
Cholesterol
Phospholipids
Fat-soluble vitamins (A, D, E, K)
236
Detergents made from?
Cholesterols
237
Where are detergents formed?
In liver
238
Where do further modifications of detergents occur?
In GI tract
239
Types of bonds that join -COOH end of FA to other molecules?
Ester bonds
240
Types of detergents?
Cholate
Deoxycholate
MAG
Lyso-phosphotidylcholine
241
One of the functions of detergents?
Provide access for lipases to cleave FA's form TG's, cholesterols, phospholipids
242
How are FA's removed from TG's?
Via lipases in the intestines
243
Which FA is cleaved in the intestines?
Middle FA
244
Function of bile acids?
Emulsify insolubile TG's and break them down to where intestines can absorb them
245
FA's that can penetrate the membrane and be readily absorbed?
Small FA's
Short chain FA's
Medium chain FA's
246
What is a chylomicron?
Lipoproteins that are TG rich
Contain specific apo-proteins to mediate uptake in liver and adipose tissue
247
Function of chylomicrons?
Transport dietary lipids to destination
248
TG's sent to liver via chylomicrons are repackages into what?
VLDL
249
In terms of fat storage:
Insulin
Stimulates uptake of fat storage in adipose tissue
250
How does insulin stimulate uptake of fat?
1)
2)
3)
1) Suppress FA release from existing FA's
2) Acceleration of glycolysis (increased DHAP for TG synthesis)
3) Enhance lipoprotein lipase in adipose capillaries
251
Role of Lipoprotein lipase
Digest TG's into FFA's and release those free fatty acids for uptake
252
Regulation of Lipoprotein Lipase: Fed State
Adipose
Muscle
Upregulated in adipose tissue
Downregulated in muscle
Cardiac muscle has higher LPL than skeletal muscle
253
Regulation of Lipoprotein Lipase: Fasted State
Adipose
Muscle
Upregulated in muscle via epinephrine
Downregulated in adipose tissue
254
Where is Lipoprotein lipase found in body?
Endothelial cells of capillary walls (in lumen of capillaries)
254
How is lipoprotein lipase anchored to endothelial walls?
Heparan sulfate
255
256
Fatty Acid Synthesis:
Location?
In liver
257
What product of glycolysis must be increased to form FA's?
Acetyl CoA
258
What is Acetyl-CoA combined with to form TG's?
Glycerol Phosphate
259
Define beta oxidation
Fatty acid degradation
260
FA Substrate Formation:
Formed where?
Cytosol of cells
261
FA Substrate Formation:
Acetyl CoA formed where?
Mitochondria
262
FA Substrate Formation:
How is AceCoA moved BACK to cytosol?
Citrate/Pyruvate Shuttle
263
Steps in Citrate/Pyruvate Shuttle
1)
2)
3)
4)
5)
6)
1) Pyruvate enters mitochondria
2) Pyruvate becomes oxaloacetate (first step of gluconeogenesis)
(via Pyruvate Carboxylase)
3) AceCoA formed and combines with Oxaloacetate = forms citrate
4) Citrate leave mitochondria - cleaved BACK to AceCoA
5) Reducing agents form Palmitoyl CoA
6) AceCoA used to synthesize Palmitate
264
AceCoA is converted into?
Malonyl CoA
265
What enzyme converts AceCoA into Malonyl CoA?
Acetyl CoA Carboxylase
266
Acetyl CoA Carboxylase inhibited by?
Palmitoyl CoA
267
Acetyl CoA Carboxylase activated by?
Citrate
268
Main enzyme to grow FA chain?
Fatty Acid synthase
269
What is attached to FA chains to transport around during synthesis?
Phosphopantetheine
270
Phosphopantetheine enzymatically bound to?
Acyl Carrier Protein (ACP) domain
271
Pantothenic acid is which Vitamin?
Vitamin B5
272
Fatty Acid Synthase typically makes?
Saturated FA's
273
Enzyme to introduce double bonds to make unsaturated FA's
Desaturases
274
Overall types of reactions in FA synthesis
Reduction
Dehydration
Reduction
Condensation
Translocation
275
TG's synthesized from?
DHAP
276
Where is glycerol phosphate made?
Liver
277
What is glycerol derived from?
Breakdown of TG's in chylomicrons and VLDL particles
278
Glycerol used as precursor for which metabolic pathway?
Gluconeogenic pathways
279
280
FA's are released for usage by?
Hormone Sensitive Lipase
281
Where does FA go once released from adipose tissue?
Binds to serum albumin in bloodstream for transport
282
TG's are converted to FA via?
Lipoprotein Lipase
283
TAG turned into DAG by?
Adipose TriGlyceride Lipase
284
Hormone Sensitive Lipase regulated by
Epinephrine
cAMP/PKA messaging
285
Rate limiting enzyme of FA release
Hormone Sensitive Lipase
286
MAG is further broken down by?
Monoglyceride Lipase
287
FA release from adipose tissue is inhibited by?
Insulin
288
Increased TG breakdown via removal of insulin
1)
2)
1) Decrease rate of phosphate removal from HSL
2) Decreasing DHAP
289
Importance of FFA's being bound to albumin in serum?
Otherwise FFA's insert themselves into membranes and disrupt/compromise membrane function
289
How are FA's brought into mitochondrial matrix of cells?
Carnitine shuttle
289
Define β-oxidation
Breakdown of FA's to AceCoA
Makes energy from fat reserves
290
Which carnitine shuttle adds carnitine to FA?
Carnitine Palmitoyl Transferase I (CPT1)
291
Which carnitine shuttle removes carnitine from FA?
Carnitine Palmitoyl Transferase II (CPT II)
292
What inhibits Carnitine Shuttle?
Malonyl CoA
293
Function of β-oxidation?
Use of FA directly for energy
294
Fatty Acid CoA:
Broken down to
Via enzyme?
Enoyl CoA
Acyl CoA Dehydrogenase
295
Enoyl CoA:
Broken down to
Via enzyme?
3-hydroxyacyl CoA
Enoyl CoA Hydratase
296
3-Hydroxyacyl CoA:
Broken down to
Via enzyme?
3-Ketoacyl CoA
3-hydroxyacyl CoA dehydrogenase
297
3-ketoacyl CoA:
Broken down to
Via enzyme?
Acetyl CoA
β-Ketoacyl-CoA thiolase
(exchange)
298
How does acyl CoA dehydrogenase act?
Oxidizes double bond between 𝛼 and β carbons
299
Result of Acyl CoA Dehydrogenase
Double bond formed
FADH2
300
Variants of Acyl-CoA Dehydrogenase
VLC acyl-CoA Dehydrogenase
LC acyl-CoA Dehydrogenase
MC acyl-CoA Dehydrogenase
SC acyl-CoA Dehydrogenase
301
Function of Enoyl CoA Hydratase
Hydrate across double bonds
302
Function of 2-hydroxyacyl CoA Dehydrogenase
Oxidation of β-carbon hydroxyl
303
β-Ketoacyl CoA Thiolase
Produces AceCoA
304
Where are VLCFA's initially broken down
Peroxisomes
305
Enzyme that allows odd double bonds (odd chain FA's) to be oxidized?
cis Δ3 enoyl CoA isomerase
306
Function of cis Δ3 enoyl CoA isomerase?
Moves double bond in odd chain FA to 2-position
307
Even chain FA's - double bonds at even positions:
Enzymes that reduce double bonds
2,4 dienoyl-CoA Isomerase
308
Function of 2,4 dienoyl-CoA Isomerase?
Reduce double bonds to one
Isomerase moves it into position to be handled by β-oxidation
309
Regulation of Acetyl CoA Carboxylase
Activated by citrate
Inhibited by Palmitoyl CoA
310
Function of Insulin in regulation of AceCoA Carboyxlase
Will activate it via protein phosphatase (removed phosphate from phosphorylated Carboxylase)
311
Function of Glucagon and Epinephrine on regulation of AceCoA Carboxylase
Will activate AMPK Kinase - phosphorylates Carboxylase to inactivate it
312
Function of AMP on regulation of AceCoA Carboxylase
Allosteric activator of AMP-activated protein kinase
Phosphorylates AceCoA Carboxylase
313
Regulation of FA Synthesis/Oxidation via Malonyl CoA
Blocks Carnitine Shuttle in Mitochondria
Prevents LCFA from entering Mitochondrial Matrix
314
FA Synthesis active
β-oxidation inhibited
315
FA Synthesis inactive
β-oxidation active
316
Acetyl CoA Carboxylase 1
Regulates FA Synthesis
317
Acetyl CoA Carboxylase 2
Regulates β-oxidation
318
NEFA
Non-Esterified FA's
319
Ketone bodies made in response to?
Long increase in FA's for prolonged period of time
320
Known Ketone bodies
3-Hydroxy butyrate
Acetoacetate
321
Function of ketone bodies
Alternate way to move energy among organs during prolonged fast
322
Ketone bodies formed?
In liver
323
Amount of time for ketone bodies to fully ramped up for production in liver
2-3 days
324
Rate limiting enzyme in Ketone body synthesis
HMG-CoA Synthase
325
Formation of Ketone bodies
2 AceCoA condensed to make Acetoacetyl CoA
3rd molecule of AceCoA used to make 3-hydroxymethylglutaryl-CoA
326
Formation of 3-hydroxymethylglutaryl CoA by which enzyme?
HMG-CoA synthase in mitochondria
327
Enzyme to catalyze HMG-CoA to AceCoA and Acetoacetate
HMG-CoA Lyase
328
Acetoacetate converted to?
Reduced to 3-Hydroxybutyrate
329
When ketone bodies taken up in cells - what enzymes converts hydroxybutyrate and acetoacetate into Acetoacyl-CoA?
CoA transferase
Thiophorase
330
In blood, acetoacetate forms?
Acetate
331
How is acetate in blood formed?
Spontaneous decarboxylation of acetoacetate
332
Signs of high ketone body production in body
Sweet smell on breath
333
Key enzymes of glycolysis
1) Hexokinase (muscle/other)/Glucokinase (liver pancreas)
2) PFK1
3) Pyruvate dehydrogenase
334
Function of hexokinase
Phosphorylate glucose to G6P
335
Function of phosphofructokinase-1
Phosphorylates Fructose-6-Phosphate to Fructose-1,6-Phosphate
336
Function of Pyruvate kinase
Convert Phosphoenolpyruvate to Pyruvate
337
Enzyme in glycolysis that controls flux of glucose through glycolysis
PFK-1
338
Enzyme that maintains balance between glycolytic flux and other metabolic pathways
Pyruvate Kinase
339
Define: Glycogenolysis
Glycogen breakdown into glucose
340
Define: Gluconeogenesis
Synthesis of glucose in liver (and kidney)
341
During fasting, what is primary source of energy
Fat
342
RBC's dependent on which metabolic pathway to funtion
Glycolysis - unable to function without it
No mitochondria = unable to undergo β-oxidation
343
Possible fates of pyruvate
Lactate
Acetyl-CoA
Oxaloacetate
Ethanol
Alanine
344
Function of TCA cycle
Breakdown acetate to CO2 for energy
Produce reducing equivalents (NADP or FADH2)
345
Sources of AceCoA
Glycolysis
β-oxidation
Ketone bodies
346
FA's enter mitochondria for oxidation via
Carnitine Shuttle
347
Vitamins needed for Pyruvate Dehydrogenase
Vit B1, B2, B3, B5
348
Other cofactors needed for Pyruvate Dehydrogenase
Lipoic Acid
349
If deficiencies in Vitamins, results on oxidative metabolism
Reduced OxPhos and reduced energy to cells
350
Structure of CoA
Coenzyme A
Pantothenic Acid
351
Enzymatic Activities of Pyruvate Dehydrogenase:
Decarboxylase
Pyruvate reacted with TPP
Loss of CO2
352
Enzymatic Activities of Pyruvate Dehydrogenase:
Lipoaminde Reductase/Transacetylase
TPP donates bound hydroxyethyl to lipoyl moiety
Coenzyme A replaces sulfur for lipoyl sulfur = Reduced lipoyl/AceCoA
353
Enzymatic Activities of Pyruvate Dehydrogenase:
Dihydro-lipoyl Dehydrogenase
354
Cofactors needed for Pyruvate Dehydrogenase
Thiamine Pyrophosphate
Lipoic Acid
CoA
FAD/FADH2
NAD+/NADH
355
