Energy Balance Flashcards
1
Q
Two theories of appetite and satiety
A
Glucostatic theory
Lipostatic theory
2
Q
Function of leptin
A
Leptin is secreted by adipose cells when fat stores increase. It inhibits the release of neuropeptide Y which signals to the hypothalamic feeding center.
Makes you feel FULL.
3
Q
Ghrelin
A
A peptide hormone secreted by stomach during fasting. Makes you feel HUNGRY.
4
Q
How do we measure energy expenditure?
A
Oxygen consumption is used as a proxy for energy expenditure
Metabolic rate = liters of oxygen consumed per day * kilocalories per liter of oxygen
5
Q
Respiratory exchange ratio
A
Ratio between the volume of carbon dioxide produced per volume of oxygen used during metabolism
Each glucose molecule produced 6CO2 and 6O2, a 1:1 ratio
But fat molecules produce more O2 for every carbon… so LESS THAN 1
6
Q
Glucostatic Theory
A
The theory that states that when blood glucose decreases, satiety center (in hypothalamus) is repressed and feeding center is dominant.
7
Q
LIpostatic Theory
A
The theory states that fat stores help modulate body weight. Adipocytes secrete leptin, a hormone that signals satiety, so more fat equals more leptin.
8
Q
Neuropeptide Y
A
Signals to hypothalamic feeding center to intake more food!! The signal that represses it is Leptin.
9
Q
Peptides that increase food intake
A
Ghrelin (stomach)
NPY and Agouti-related protein (hypothalamus)
Orexins (hypothalamus)
10
Q
Peptides that decrease food intake
A
CCK (small intestine, neurons)
GLP-1 (intestines)
PYY (intestines)
Leptin (adipose)
CRH (hypothalamus – this is a releasing hormone!)
alpha-MSH (hypothalamus)
CART and POMC (hypothalamus - ‘cocaine-and-ampehtamine-regulated transcript’… presumably activated by cocaine / speed, which is why people on cocaine / speed are so skinny!)
11
Q
Sources of energy input
A
DIET
Hunter/appetite, satiety, social and psych factors
12
Q
Forms of Energy output
A
- HEAT
2. WORK
13
Q
components of heat as energy output
A
either unregulated (waste) or thermoregulation
14
Q
components of work as energy output
A
transport across membranes
mechanical work e.g. movement
chemical work e.g. growth and energy storage via chemical bonds or high-energy phosphate bonds
15
Q
RER for energy derived totally from fats?
A
0.7
16
Q
RER for energy derived totally from carbs?
A
1.0
17
Q
Biomolecules that we eat are either…
A
- Used to make energy (ATP, phosphocreatine, NADPH)
- Used to make stuff (like proteins, cytoskeleton)
- Stored (as glycogen or fat)
18
Q
Difference between NADPH and NADH
A
NADH is used in the electron transport chain to make ATP
NADPH is a phosphorylated version of NADH that carries electrons, but to MAKE molecules, such as lipids, via “reductive biosynthesis”
19
Q
Absorptive / Fed State
A
Nutrients enter blood from digestive tract, cells either USE what they need or STORE for later
20
Q
Postabsorptive / Fasted state
A
Digestive tract is empty so nutrients enter blood from stored fat, glycogen, and gluconeogenesis
ALL CELLS mobilize resources: only liver and adipose supply nutrients to the rest of the body
21
Q
What are the “generous” organs?
A
Liver, adipose
They will share their energy stores with other organs
22
Q
What does heart typically use as a stored energy source?
A
Fats
Long term, sustainable source of energy
23
Q
What does muscle typically use as a stored energy source?
A
Glycogen
Can immediately consume glucose for mechanical work
24
Q
What does the brain typically use as a stored energy source?
A
Trick question, nothing! The brain uptakes free glucose from the blood. It gets first dibs on glucose, always.
25
Liver during absorptive state (feeding)
Receives GLUCOSE and AMINO ACIDS
(Glucose can be stored as glycogen or broken down to acetyl groups to make fatty acids)
Sends LIPIDS to adipose as VLDLs
26
VLDL
Very low density lipoprotein
27
Adipose during absorptive state (feeding)
Receives TRIGLYCERIDES packaged as chylomicrons in intestines, along with any excess GLUCOSE
28
Skeletal Muscle during absorptive state (feeding)
Receives GLUCOSE to store as glycogen
29
All tissues during absorptive state (feeding)
Use AMINO ACIDS to make proteins
| Use GLUCOSE immediately according to needs
30
What can happen to an acetyl (or acetyl CoA) group?
1. Enters TCA to make NADH/FADH2
2. Used to make cholesterol
3. Pasted together to make fatty acid chains (which is why fatty acids are always an even number of carbons)
31
What are the enzymes involved in fed-state metabolism
Glycogen synthase
Prompted by insulin
32
What enzymes are involved in fasted-state metabolism
Glycogen Phosphorylase
Prompted by glucagon: tells this enzyme to make free molecules of G6P
33
Fatty Liver Disease
When triglycerides are not properly transported from liver to adipose, so stay stuck in liver
34
Absorptive Fed State (General Synthesis of what everything is doing)
1. Nutrients from gastrointestinal tract go into blood
2. Muscle takes up glucose and amino acids
3. Hepatocytes take AMINO ACIDS to make proteins, keto acids, fatty acids, and triglycerides
4. Hepatocytes take GLUCOSE to make glycogen, GAP, and triglycerides
5. Adipose takes up Triglycerides from liver
6. Adipose takes up glucose, made into fatty acids or GAP
7. ALL TISSUES use glucose as energy source
35
How is excess glucose stored in the liver?
How is excess glucose stored in adipose?
How is excess glucose stored in muscle?
LIVER: Glycogen
ADIPOSE: Triglycerides (sent from liver)
MUSCLE: Glycogen
36
What can an amino acid be used for during fed-state metabolism?
1. Translation / make proteins
| 2. Oxidized into keto acids
37
Chylomicrons
The way triglycerides are packaged in the digestive tract and sent directly to adipose tissue for storage
Include cholesterol, lipoproteins, lipid complexes
HUGE - so big that cannot go via bloodstream
38
Transport and Fate of Dietary Fats (step by step)
1. Bile salts help break down dietary fats
2. Intestinal epithelial cells absorb cholesterol, lipoproteins, lipid complexes into chylomicrons
3. Chylomicrons transported to blood via lymph system
4. Lipoprotein lipase converts triglycerides into free fatty acids and glycerol
5. Adipose cells reassemble free fatty acids and glycerol into triglycerides for storage. Other cells use free fatty acids for energy, EXCEPT THE BRAIN.
6. Chylomicron remnants and HDL-C enter liver, creating LDL and VLDL. Some new cholesterol recycled in new bile salts.
7. LDL-C transported via blod to most cells, where cholesterol is used for synthesis.
39
What can cholesterol be used for?
1. Steroid hormones
2. Phospholipid bilayer component
3. Making new bile salts
40
What energy source does the liver prefer?
Fats!
It wants to spare glucose for the brain / NS; in general this organ DELIVERS glucose to the body... so it won't use glucose if it can help it
Per the old adage: "Don't get high on your own supply"
41
Limitations on glycogen and fat storage
Glycogen storage is LIMITED
Fat storage is UNLIMITED
This is why we as humans have a problem with obesity, not being super jacked / buff versions of ourselves
42
What enzyme turns acetyl CoA into fatty acids?
fatty acid synthatase
43
Triglyceride
One glycerol plus three fatty acids
Glycerol comes from glucose intermediate in glycolysis
Fatty acids come from acetyl CoA (this follow pyruvate oxidation)
44
Key role of the liver
To maintain blood glucose homeostasis
45
Postabsorptive/Fasted State Overview
1. Glycogenolysis (glucose released by liver for other tissues)
2. Lipolysis
3. Gluconeogenesis from lactic acid / pyruvate (can take place liver, kidney, AND RBCs)
4. amino acid breakdown in extra hepatic tissues
* * in liver, amino acids used as substrates for gluconeogensis
5. Oxidation of fatty acids to make ATP
6. Oxidation of lactic acid by cardiac muscle
7. Amino acid oxidation in liver
8. Use of ketone bodies for ATP production
9. Glycogenolysis in skeletal muscle for use in skeletal muscle
46
What happens to glucose in fasted state?
1. Released by liver for other tissues
2. Created from lactic acid / pyruvate in liver, kidney, and RBCs
3. Created from amino acids in liver
4. Released by muscle FOR ITSELF (selfish!)
47
What happens to amino acids in fasted state?
1. Broken down in extra hepatic tissues for protein synthesis, energy, etc
2. Used in liver to make glucose
3. Oxidized in liver to make Keto acids, which can be used to make acetyl CoA and ATP
48
What happens to fats in fasted state?
1. Generally broken down for energy
| 2. Oxidized to produce ATP
49
What is the heart doing during fasted state that is unique?
Oxidizing lactic acid
50
Cori Cycle
When lactic acid produced by muscles is moved to liver and turned into glucose
** This also takes place in kidneys, RBCs!!
51
Where are ketone bodies made?
IN THE LIVER
Then transported to NS, other tissues, heart
Made from fatty acids
52
Energy can come from which processes in the fasted state....?
1. Glycogenolysis
2. Amino acid oxidation
3. Lipolysis
4. Gluconeogensis
5. Ketogenesis
53
Glycogenolysis (General)
Glycogen breakdown, only in liver and skeletal muscle
Hepatic glucose comes in first, but after a few hours is 'spared' for the NS (so runs out)
Muscle glycogen ONLY USED in muscle cells
54
Amino Acid Oxidation (General)
Come from breakdown of proteins, only occurs during a prolonged fast
55
Lipolysis (General)
Breakdown of fats
Triglycerides broken down to fatty acids and glycerol
Glycerol can be converted to glucose in the liver
Fatty acids can be broken down into acetyl CoAs / oxidized as needed into ketone bodies
56
Gluconeogenesis (General)
Make glucose from lactic acid or some amino acids
57
Ketogenesis (General)
Another energy source for the brain
58
Glycogenolysis (in depth)
Glycogen is a branched polymer of glucose: two different enzymes liberate glucose in the form of G6P from this branching.
The more important enzyme is Glycogen phosphorylase, which removes G1P from glycogen chain at UNBRANCHED points. An isomerase then converts to G6P and reenters glycolysis.
Monomers of unphosphorylated glucose are removed at branched points...we don't need to know this.
59
Does the liver have hexokinase? Why or why not?
NO! Hexokinase is less specific, high affinity glucose enzyme. Liver only has low affinity glucokinase (specific for glucose).
Liver is not a high priority glucose taker. It's like the grandmother who takes the food last at the family dinner!
60
What enzyme removes glucose from glycogen?
Glycogen phosphorylase! (takes out of glycogen to make G-1-P, which is converted to G-6-P)
61
What enzyme pieces glucoses together to make glycogen?
Glycogen synthase!
62
Amino Acid Oxidation (Biochemistry)
FIRST, amino acids must be deaminated to undergo oxidation. This produces ammonia and an organic acid.
The organic acid can go through glycolysis or TCA.
SECOND, the ammonia is caustic and must be converted to ammonium and then urea, excreted as waste.
63
Deamination of amino acid produces...
1. Ammonia
2. Organic acid
3. NADH! (and H+)
64
Lipolysis (step-by-step)
1. Lipases digest triglycerides into glycerol and 3 fatty acids.
2. Glycerol becomes substrate in glycolysis.
3. Beta-oxidation clips 2-carbon units from fatty acids.
4. Acyl units become acetyl CoA and used in TCA.
65
Beta Oxidation
The breakdown of fatty acids into acyl / acetyl groups
66
What is the MAJOR source of energy in lipolysis?
Beta oxidation (produces acetyl CoA)
67
What is a MINOR source of glucose in lipolysis?
Glycerol (enters glycolysis)
68
Beta Oxidation produces...
1. Acyl units / acetyl CoA
| 2. NADH and FADH2!
69
Where does Beta oxidation take place?
In the mitochondria! (Since FADH2 is involved you know it's near the membrane)
70
Story of Fasting for Whole Body
1. Liver glycogen becomes glucose. Free fatty acids become ketone bodies or glucose. All may take.
2. Adipose lipids become free fatty acids and glycerol that enter blood. All may take.
3. Muscle glycogen used for energy in muscle. Muscles also use fatty acids and break down their proteins to amino acids that enter the blood. ONLY FOR MUSCLE.
4. Brain uses only glucose and ketones for energy.
71
Glycolysis vs Gluconeogenesis
Glycolysis is ten steps to make glucose. It occurs in all cells.
Gluconeogenesis is a nine step REVERSE of glycolysis starting from pyruvate (amino acids, lactate) or glycolytic intermediates (amino acids, glycerol) to make G6P. It occurs in the LIVER and the KIDNEYS only.
72
What steps are different between glycolysis and gluconeogenesis? Are these steps reversed?
Steps 1, 3, and 10 of glycolysis, aka the irreversible steps.
They are NOT reversed. They use entirely different enzymes. (The other steps are reversed.)
73
Gluconeogenesis "Step 1" Variation
In glycolysis, hexokinase would phosphorylate glucose using ATP, a high-energy molecule.
But G-6-P is not high energy enough for a substrate-level phosphorylation. So cleave the Phosphate group with a phosphatase instead (glucose-6-phosphatase).
74
Gluconeogenesis "Step 3" Variation
In glycolysis, PFK uses ATP to phosphorylate F-6-P, creating a bisphosphate.
But F-1,6-bisphosphate is not a high energy compound, so use a phosphatase to cleave the phosphate, making F-6-P (Fructose 1,6-bisphosphatase-1).
75
Gluconeogenesis "Step 10" Variation
In glycolysis, PEP (a high-energy compound) phosphorylated ADP to make ATP and pyruvate.
However here the reaction must take TWO steps. ATP is used to convert pyruvate to oxaloacetate, then GTP is used to convert that into PEP.
So TWO molecules of ATP are used to reverse this step, when to make the compound one ATP was created.
76
Why do Type II diabetes drugs block gluconeogenesis?
Because cells have become insensitive to glucose, the body does not realize that resources are plentiful so are expelling glucose - and going through a lot of gluconeogenesis unnecessarily!
77
Where does lipolysis occur?
ALL CELLS except liver and brain
78
Where does ketosis occur?
Just the liver!
79
Ketosis
Fatty acids processed into ketones in the liver, these can be used as a second energy source by the brain
80
What are the products of ketosis? And how many are acidic?
Acetoacetate
3-beta-hydroxybutyrate
Acetate
2/3 are acidic! All but acetate
81
Ketoacidosis
Uncontrolled ketone production; a complication of Type I diabetes, lowers blood pH (high acid makes it difficult for cells to reach potential & fire)
Also causes dehydration and iron imbalances
82
Glucose Sparing
Lipolysis occurs to allow for ATP production in cells when glucose is limited or being spared (so that brain gets dibs on glucose)
Triglycerides in adipose tissue catabolized to glycerol and fatty acids
83
When is glycerol an important source of glucose?
Only during fasting!
84
Fasted v Fed State Carbs
Fed:
1. Used immediately glycolysis / TCA
2. Lipoprotein synthesis in liver
3. Stored as glycogen in liver & muscle
4. Excess converted to fat & stored in adipose
Fasted:
1. Glycogenolysis in liver & kidney
85
Fasted v Fed State Proteins
Fed:
1. Protein synthesis most tissues
2. Deaminated in liver and used for energy
3. Excess converted to fat & stored in adipose
Fasted:
1. Proteins broken down into amino acids
2. Gluconeogenesis uses deaminated amino acids
86
Fasted v Fed State Fats
Fed:
1. Lipogenesis in liver and adipose
2. Cholesterol used for steroids / bilayers
3. Fatty acids used for lipoprotein and elcosanoid synthesis
Fasted:
1. Lipolysis
2. Beta oxidation
87
What hormone(s) govern the homeostatic range of glucose?
Glucagon and insulin
88
Endocrine Gland function of pancreas
Secrete glucagon and insulin into blood from Islets of Langerhans
Alpha cells - glucagon
Beta cells - insulin, amylin
D cells - somatostatin
89
Exocrine function of pancreas
Secrete digestive enzymes via duct to small intestines
90
What does insulin signal for?
1. Glucose oxidation
2. Glycogen synthesis
3. Fat synthesis
4. Protein synthesis
91
What does glucagon signal for?
1. Glycogenolysis
2. Gluconeogenesis
3. Ketogenesis
NOTE: Lipolysis is NOT HERE!
92
Hormones when glucose above homeostatic range
High insulin
93
Hormones when glucose in homeostatic range
Low to moderate insulin
94
Hormones when glucose at low end of range
Low insulin plus presence of glucose
95
Hormones in the fed state
1. Eat a meal
2. GI tract distends, stretch receptors fire, and PARAsympathetic NS stimulates insulin secretion
3. Presence of carbs in GI lumen stimulates endocrine cells of small intestine, which release GLP-1 and GIP, stimulating insulin secretion
4. nutrient digestion and absorption increase amino acids and plasma glucose, stimulating insulin secretion
** Increase in plasma glucose INHIBITS alpha cells
96
Which autonomic NS inhibits insulin secretion?
Sympathetic
97
Insulin Signaling (For adipose / skeletal muscle)
1. Insulin binds to tyrosine kinase receptor
2. Receptor phosphorylates insulin-receptor substrates
3. Second messenger pathway alter protein synthesis and existing proteins.
4. Glucose transport proteins are sent to cell surface via exocytosis, promoting glucose uptake.
98
What membrane transporter protein is sent to cell surface in adipose / skeletal muscle?
GLUT-4
Facilitated diffusion, not as high affinity as transporters in the NS
ONLY FED STATE!
99
What more complicated things does insulin signaling do within a cell?
Signals for changes in gene expression (MAP kinase, PTEN SHIP2, etc)
Effects activity of enzymes in glycogen synthesis
Hexokinase traps glucose to make G6P
100
Insulin in the Liver (Fed & Fasted)
1. In taste state, hepatocyte makes glucose and transports out using GLUT-2 transporters.
2. In fed state, more glucose outside of cell than in, so glucose comes into cell via GLUT-2, where glucokinase phosphorylates to G-6-P.
GLUT-2 = facilitated diffusion
101
Why are proteins only synthesized (aka translated) when there are lots of resources?
Because adding each amino acid to the peptide chain requires several molecules of GTP. This can only be done with lots of resources!
102
Beta Cell Insulin Release (step by step)
1. Glucose enters via GLUT2.
2. Glucose becomes G6P by glucokinase.
3. Some glucose is metabolized via cellular respiration, leading to ATP > ADP.
4. Increased ATP binds to K+ leak channel.
5. K+ leak channel closes, and K+ builds up in cell, depolarizing the cell.
6. Voltage gated Ca2+ cells open, calcium enters.
7. Calcium binds to SNARES in vesicles.
8. Vesicles exocytose and insulin is secreted.
103
What maintains the proportionality of the amount of insulin secreted relative to the amount of excess glucose in the blood?
The LOW AFFINITY of transporters / enzymes. The cell will equilibrate to blood glucose levels because the GLUT-2 transporters are passive and not high affinity. Glucokinase also has low affinity, so will never over signal for insulin release.
104
When do you see zero insulin release?
Type 1 diabetics
105
Low Blood Glucose Pathway (step by step)
1. Blood glucose down
2. Beta cells of pancreas are inhibited, decreasing insulin signal to muscle, adipose; these release lactate, pyruvate, amino acids, fatty acids, all of which head to the liver for processing
3. Plasma glucose down and plasma amino acids up, signaling to alpha cells, which increase glucagon signaling to liver
4. Liver takes materials and does glycogenolysis, gluconeogenesis, ketosis (for use by brain, other tissues)
5. Blood glucose rises
106
Glucagon Signaling Pathway (Liver) occurs during...
fasting
107
Glucagon pathway (Liver)
1. Glucagon binds to GCPR, heterotrimer talks to adenylate cyclase
2. cAMP activated
3. PKA activated
4. phosphorylase kinase activates, glycogen synthase deactivated
5. G1P created, made into G6P, gluconeogenesis
108
what signaling pathway mimics the glucagon pathway in muscle and liver?
Epinephrine
Signal during exercise
109
Four main hormonal controls
1. Glucagon
- glycogenolysis, gluconeogenesis
2. Epinephrine
- glycogenolysis, gluconeogenesis, AND lipolysis
3. Cortisol
- gluconeogenesis, lipolysis, inhibits glucose uptake (aka everything except glycogenolysis)
4. Growth Hormone
- same as cortisol
110
Energy homeostasis during moderate exercise
Glucose gradually goes down
Insulin goes down same rate of glucose
Glucagon goes way up only when insulin levels low
* Remember, epinephrine is involved, stimulating the liver
111
Type I Diabetes
"Juvenile"
Caused by autoimmune destruction of beta cells; NO insulin is produced
Trigger is unknown, age of onset varies, may be genetic
112
Type II Diabetes
"Adult onset"
Caused by chronic high blood glucose (genetic predisposition + lifestyle)
Downregulation of insulin receptors results in HIGH insulin levels; though in advanced cases, insulin impaired
113
Diagnostic Criteria for Diabetes for "Normal" person
Fasting blood glucose less than 100 mg/dL
| 2 hour post test, glucose less than 140 mg/dL
114
Diagnostic criteria for diabetes for pre-diabetes
Fasting blood glucose 100-125 mg/dL
| 2 hour post test, glucose 140-199 mg/dL
115
Diagnostic criteria for diabetes for diabetic
Fasting blood glucose >125 mg/dL
| 2 hour post test, glucose >199 mg/dL
116
When insulin release is impaired...
The body thinks that we are starving, but the only problem is lack of signal
Leads to tissue loss, hyperglycemia, polyphagia (ketosis)
117
Hyperglycemia leads to...
Metabolic acidosis, dehydration
118
Causes of metabolic acidosis, dehydration
1. ACIDOSIS: Oveproduction of ketones, up ventilation and urine acidification + hyperkalemia
2. DEHYDRATION: Increase glucose in urine leads to diuresis, dehydration, attempt to compensate leads to increased blood pressure, which leads to circulatory failure / death
