Exam 2: Metabolism Flashcards
1
Q
What are the 9 Essential Amino Acids?
A
- Histidine
- Isoleucine
- Leucine
- Lysine
- Methionine
- Phenylalanine
- Threonine
- Tryptophan
- Valine
2
Q
What are the 9 Non-essential Amino Acids?
A
- Alanine
- Arginine
- Asparagine
- Aspartate
- Glutamate
- Glutamine
- Glycine
- Proline
- Serine
3
Q
What are the 2 Conditionally Essential Amino Acids (& their source)?
A
- Cysteine (from methionine)
- Tyrosine (from phenylalanine)
4
Q
What are the important Enzymes in the digestion of proteins (and their location of origin):
–Name 6
A
- Pepsin (activated in stomach)
- Trypsin (1ST! activated in S.I.)
- Chymotrypsin (activated in S.I.)
- Elastase (activated in S.I., by Trypsin)
- Carboxypeptidase A (S.I.)
- Carboxypeptidase B (S.I.)
–Free AA’s activate trypsin in SI. Trypsin activates all other enzymes.
5
Q
Name of the major membrane protein that transports free amino acids into enterocyte cells in the small intestine:
A
PEPT1: accounts for 60%
6
Q
How are free AA’s transported after absorption into enterocytes
A
Via portal vein to the liver
7
Q
What happens to proteins in the liver?
A
- De-amination (remove Nitrogen): in Mitochondria of hepatocytes. Urea Cycle
- Carbon backbone is used for catabolism (breaking down for energy) or anabolism (building up proteins)
8
Q
What determines whether amino acids will be catabolized or anabolized?
A
Insulin
–High insulin = increased ANABOLISM (protein synthesis)
9
Q
What are the 2 Ketogenic Amino Acids?
A
- Leucine
- Lysine
10
Q
What are the 5 Amphibolic Amino Acids?
A
- Phenylalanine
- Isoleucine
- Threonine
- Tryptophan
- Tyrosine
11
Q
What is a peptide?
A
Molecule composed of between 2-50 amino acids… linked by peptide bonds
-ex: oligopeptides: 3-50
-polypeptides: 50-100
12
Q
Summarize the TCA cycle
A
-Pyruvate
-Acetyl Co A
(combines with Oxaloacetate to form…)
-Citrate
-Isocitrate
-Alpha Ketoglutarate
-Succinyl-CoA
-Succinate
-Fumarate
-Malate
-Oxaloacetate
13
Q
What amino acids are most abundant in serum?
Function?
A
-Glutamine
-Glycine
-Alanine
- These amino acids are used to transport Nitrogen through blood, so that blood PH does not change
- Their C-skeleton is used by non-liver cells for energy
14
Q
What are the 2 major fates of Amino Acids? Why?
A
- Protein
- Energy
… because they are not readily able to be stored in our bodies
15
Q
What is the anabolic state?
A
Amino acids are largely converted into serum proteins by the liver OR skeletal muscle protein (due to exercise or healing)
16
Q
What is the catabolic state?
A
Amino acids are immediately metabolized for energy and the reminder (stripped Nitrogen) is excreted
-N stripped via urea cycle and excreted
-C skeleton converted into forms that can enter TCA cycle or gluconeogenesis
17
Q
Aspartate and Asparagine are readily converted into which intermediate of the TCA cycle (via removal of N)
A
Oxaloacetate
18
Q
Glutamate and Glutamine are readily converted into which intermediate of the TCA cycle (via removal of N)?
A
Alpha-Keo-glutarate
19
Q
Alanine is readily converted into which intermediate of the TCA cycle (via addition of N)?
A
Pyruvate
20
Q
What enzyme converts glutamine into glutamate?
A
Glutaminase
21
Q
What enzyme converts glutamate into alpha keto glutarate?
A
Glutamate dehydrogenase
22
Q
What enzyme converts Alanine into Pyruvate?
A
Alanine transaminase
23
Q
What enzyme converts Asparagine into Aspartate?
A
Asparaginase
24
Q
What enzyme converts Aspartate into Oxaloacetate?
A
Aspartate Transaminase
25
What are the Steps of the Urea Cycle?
1. Glutamine-->Glutamate
**brings ammonia into mitochondria
2. Carbomyl-Phosphate
3. Citrilline
(Add Arginine-->Aspartate. 2nd N)
4. Argino-succinate
(Fumarate prod. Recycled into TCA)
5. Arginine
(Urea)
6. Ornithine
26
Which substrates of urea cycle occur in the mitochondrial matrix of hepatocytes (vs cytosol)?
Mitochondria:
-Carbomyl-Phosphate
-Citrilline (transported into cytosol)
-Ornithin (transported into cytosol)
27
How long after a meal is the fed state?
0-3 hours
28
How long after a meal is the Post-absorptive state?
3-12/18 ish hours
29
How long after a meal is the fasting state?
18 hours - 2 days
30
How long after a meal is the starvation state?
Fully adapted state lasting 2+ weeks
31
Predominant Energy Substrate in Dif. phases:
BRAIN
Fed: Glucose
Post -Absorptive: Glucose
Fasting: Glucose
Starvation: Ketones
32
Predominant Energy Substrate in Dif. phases:
Liver
Fed: Glucose
Post -Abs.: Glycogen --> Glucose/ FA's
Fasting: Fatty Acids
Starvation: Fatty Acids
33
Predominant Energy Substrate in Dif. phases:
Adipose
Fed: Glucose
Post -Absorptive: Fatty Acids
Fasting: Fatty Acids
Starvation: Fatty Acids
34
Predominant Energy Substrate in Dif. phases:
Muscle
Fed: Glucose
Post -Abs. : Glycogen --> Glucose
Fasting: Fatty Acids
Starvation: Ketones/ Fatty Acids
35
What is a Ketone?
An alternative fuel for the body that is made when glucose is in short supply. Made in the mitochondria of the Liver (as a result of FA degradation)
--ketones are used for energy during fasting, long periods of exercise, or when you don't have as many carbohydrates
36
What promotes Ketogenesis?
During prolonged starvation/fasting/diabetes, oxaloacetate is depleted in the liver due to its use in gluconeogenesis. So it cannot combine with Acetyl-coA to become Citrate for TCA cycle...
so:
ACoA build up in the Liver mitochondria!
37
Name 3 examples of Ketone bodies:
1. Acetone
2. Acetoacetate
3. Beta-hydroxybutyrate
38
Why can't the liver use ketones for energy?
The SCOT (succinyl-coA 3 ketoacid coA) is not expressed in the liver...
and this is the enzyme that attaches the coA factor onto the ketone bodies...
so that they can be utilized as energy in liver
**most other tissues express SCOT
39
Where is insulin produced?
Beta cells... in the pancreas. Specifically in the islet of Langerhans
40
Is insulin conserved in the body?
YES!
41
What is produced in the islet of Langerhans?
1. Glucagon (Alpha cells)
2. Insulin (Beta cells)
3. Somatostatin
42
What allows for the rapid release of insulin in the presence of glucose in the bloodstream?
Insulin is packaged into granules that sit at the plasma membrane, which leads to rapid (nearly instant) release during glucose-spike from food!
43
What is Incretin?
Hormone that stimulates the Beta Cells to secrete more Insulin
44
What is the Incretin effect?
If you orally ingest glucose your insulin levels will spike up much more than if you injected insulin into the bloodstream.
this suggests that the stomach/SI secretes incretins which have an additive effect, which produces a larger insulin response.
**The gap in the graph is specifically the incretin effect
45
Understand the Insulin Tolerance Test
Tests for insulin receptors uptake of glucose.
-measures blood glucose levels over time after insulin has been injected?
46
Effects of increased Insulin in Tissues:
Muscle
INCREASE glucose transport (GLUT4)
INCREASE glycogen synthesis
47
Effects of increased Insulin in Tissues:
Liver
INCREASE glycogen synthesis
INCREASE lipogenesis (making more)
DECREASE gluconeogenesis
48
Effects of Increased Insulin in Tissues:
Adipose
INCREASE glucose transport (GLUT4)
INCREASE lipogenesis (making more)
DECREASE lipolysis (mobilization)
49
Threshold carbohydrate level to achieve Ketosis:
< 20-50 CHO per day (<1 banana)
50
What is Ketoacidosis
High-levels of ketones that changes PH of blood
51
What is GLP-1?
Glucagon-like-peptide-1: Incretin hormone that stimulates insulin secretion or the "incretin effect".
Like Ozempic. Produces more insulin, which increases rate of glucose uptake and metabolism.
52
What is AMP Kinase?
(like opposite of MTOR)
Master intracellular energy sensor and metabolic "switch" regulator
--plays a pivotal role in energy homeostasis & cellular metabolism matching energy demand w/supply (ADP/ATP ratio):
INCREASES ATP PRODUCING PATHWAYS (decreases ATP using processes)
53
Name 4 ATP consuming pathways:
**Inhibited by AMP Kinase
1. Fatty Acid Synthesis
2. Cholesterol Synthesis
3. Glycogen Synthesis
4. Protein Synthesis
54
Name 3 ATP Producing Pathways:
**promoted by AMP Kinase
1. Glycolysis
2. Beta-oxidation (FA breakdown --> AcoA)
3. Glucose uptake
55
What does Glucagon do?
Stimulates glucose production to increase blood sugar levels (in low-glucose state).
Opposite function of Insulin
56
What causes loss of water weight on ketogenic diet?
Depletion of Glycogen stores = loss of water weight, because glycogen traps a lot of water and maintains a lot of water bonds
57
What are 3 fates of glucose after consumption?
1. Storage (glycogen)
2. Glycolysis (pyruvate -->TCA -->ATP)
3. Fatty acid synthesis (FA)
58
What are the stem cell origins for
-White
-Beige
-Brown
... adipocytes?
White + Beige = Mesenchymal stem cells
Brown = Muscle stem cells
59
What is a GWAS?
Genome-Wide Association study
60
What is FTO?
Fat Mass + Obesity gene:
-not causal.
A gene the distally encodes (via stimulation of IRX3 gene) for mesenchymal differentiation towards white adipocytes rather than beige adipocytes
61
What gene/s influence mesenchymal stem cell differentiation?
FTO distally influences IRX3 gene, which impacts mysenchemal differentiation into more white adipocytes rather than beige.
62
What is the difference between white, beige, and brown adipocytes?
White adipocytes have LOW mitochondrial density and largely are storage of excess glucose as fat (triglycerides).
Brown/beige adipocytes have HIGH mitochondrial density and are largely important for thermogenesis, and potentially endocrine functioning.
63
What is Caloric Restriction?
Theory that restricting calories can extend life by 20-40% (even up to 50% longer) in rodents.
There is debate in the field currently about this effect in non-human primates
64
What is a HAT? What does it do?
Histone Acetyl Transferases. (Epigenetic regulation of the genome)
--Catalyze the transfer of an acetyl group from Acetyl-CoA in nucleus.
HAT= ON = Open for transcription
65
What is a HDAC? What does it do?
Histone De-acetylases.
--REMOVE an acetyl group.
HDAC = OFF = Closed for transcription
66
What is a Histone?
They act as spools around which DNA winds to create structural units called nucleosomes.
So HATS and HDAC's wind & unwind "spool" to expose certain genes to be transcribed
67
What are 3 major categories that contribute to obesity?
1. Psychology (will-power)
2. Environment (lifestyle)
--snack food industry
3. Biology (genetics)
68
What are the 3 v's in the snack food industry?
1. Variety (a lot of flavors)
2. Value (cheap)
3. Velocity (consume fast)
69
Do adult humans have brown and white adipocytes?
All humans have ALL types of adipocytes.
70
Describe Ob/Ob mouse vs db/db mouse vs +/+ mouse:
Ob/Ob: does NOT produce leptin
db/db: no leptin RECEPTOR
+/+ : Wild Type
71
What is AMP Kinase?
Promotes ATP generating processes
-glycolysis
-glucose uptake
72
What is MTOR?
Serine Threonine-Kinase that is the major ANABOLIC regulator (builds things. Uses ATP)
--active in the presence of glucose
-protein synthesis
-new DNA
- Lipid synthesis... etc. etc. etc.
73
What is the relationship between ATP and AMP/ADP levels?
As ATP drops, AMP and ADP levels increase.
74
Treating Obesity:
Type 1:
Type 2:
Type 1: Insulin
Type 2: Diet/Exercise/ Lifestyle changes
--also drugs like metformin (acts on hyperglycemia response)
-GLP1's: increase Incretin effect/release of insulin... but might not respond completely effective if completely resistant
75
What Amino Acids have branched chains?
Isoleucine
Leucine
Valine
76
Physiology contributing to hyperglycemia:
2 Reasons
1. Muscle + Adipocytes do NOT respond well to insulin (ie. don't bring in glucose into cells effectively)
2. Liver is pumping out more glucose b/c it is running gluconeogenesis
77
What is the function of Acetyl-CoA in the Nucleus?
It is transferred onto Histone proteins and opens up DNA...
Epigenetic modification
78
Difference between Glucose Tolerance Test and Insulin Tolerance Test:
GTT: Glucose given
--healthy: should see spike and then come back down to regular levels
--T2D: spike, and then stays high for a long time
ITT: Insulin given
--healthy: glucose levels drop, and then slowly moderate to normal over time
--T2D: glucose levels do not drop much at all
79
Healthy Adipose:
Increased adipogenesis
Decreased cell volume
Increased insulin sensitivity
Decreased inflammation
**More cells but smaller
80
Unhealthy Adipose:
Decreased adipogenesis
Increased hypertrophy
Decreased insulin sensitivity
Increased low-grade inflammation
Increased macrophages infiltration
**Bigger cells. Leads to lipotoxicity (ectopic lipid deposits, and insulin resistance. Type 2 diabetes and inflammation.)
81
Physiology contributing to hyperglycemia in T2D:
1. Muscle and adipocytes do NOT respond as well to insulin (don't take glucose into the cell very effectively)
2. Liver is running more gluconeogenesis which produces more glucose in the blood stream
82
What does Metformin do?
1. Increases mobilization of GLUT4 receptors, which increases uptake of glucose into the cell
2. Decreases the rate of gluconeogenesis in the liver so that there is less glucose released into the bloodstream
83
What is the insulin mechanism?
1st and 2nd wave insulin:
1st wave-- is packaged into granules stored @ the plasma membrane, so the first spike in the chart is due to the rapid release of insulin
2nd wave: Sustained insulin response, due to reserve/secondary granules that need to move up to the plasma membrane to be release
84
How does the Insulin Receptor work?
Insulin Receptor is a TYROSINE-KINASE receptor located throughout the body.
Upon presence of insulin Tyrosine-Kinase is AUTOPHOSPHORYLATED, which causes signaling events... and it allows tyrosine kinase to be recognized and acted upon.
ex: Glut4 is brought to the cell membrane
