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PRIN 7 Fuel Metabolism Flashcards

1
Q

In what form do we store the vast amount of our energy?

A

FAT in the form of TAGs

85% of our excess fuel is fat

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2
Q

Where is glycogen stored?

A

Stored in the cytosol of liver and skeletal muscles

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3
Q

What is a TAG?

A

3 fatty acids esterified to glycerol

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4
Q

After a meal, what immediately happens to excess glucose?

A

Excess glucose is converted to fatty acids which are stored mainly as TAGs in
adipocytes

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5
Q

What does insulin do?

A

Insulin promotes glucose uptake by signalling for glucose transporters (GLUT 4) to translocate to the cell membrane.

***Gives permission for cells to take up glucose

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6
Q

What happens to glucose?

A

*Gets converted to ATP in all tissues

EXCESS:

  • some stored as glycogen
  • MOST stored as TAGs in adipose tissue
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7
Q

What does the brain use for fuel?

A

60% of the body’s glucose
(glucose hog)

CANNOT use FA’s as they can’t cross BBB

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8
Q

When do blood glucose levels fall?

A

(1) exercising

(2) between meals (but level shot NOT plummet

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9
Q

What is Glycogenolysis?

A

Cleavage of terminal glucose molecules from glycogen via

OCCURS in:

  • Liver via Glycogen phosphorylase
  • Skeletal muscle via Myophosphorylase
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10
Q

During glycogenolysis, when can glucose leave the cell?

A

When it is plain old glucose

Cannot leave till unphosphorylated

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11
Q

During glycogenolysis, when can glucose NOT leave the cell?

A

When it is phosphorylated

(NOTE: skeletal muscles can just their glucose in the phosphorylated form during glycogenoslysis

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12
Q

What is gluconeogenesis?

A

creation of glucose from non-carbohydrate precursors

  • *functions to provide glucose during fasting
  • *convert the lactate produced by anaerobic metabolism back to glucose (Cori Cycle)
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13
Q

Where does gluconeogenesis primarily occur?

A

liver

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14
Q

Which cells use the Cori Cycle?

A

Any well oxygenated cell uses the Cori Cycle to convert imported lactate back to glucose

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15
Q

What happens in response to a decrease in blood [glucose]?

A

Hepatocytes break down glycogen to produce and release glucose into the blood.

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16
Q

What substrates can be used to produce glucose via Gluconeogenesis?

A

aa, lactate, glycerol (from TAGs)

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17
Q

What can initiate GLUT4 transporters to be trans-located to the cell membrane?

A

Insulin

Contracting Skeletal Muscles via Ca2+

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18
Q

What is aerobic catabolism?

A

aka: Aerobic Respiration
occurs ONLY in mito

NOTE: pyruvate to Acetyl CoA is irreversible / no going back!

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19
Q

How is Fat used as a fuel?

A

Glycerol … (gluconeogenesis-liver) … glucose

FAs … (B-oxidation-many cells) … aceytl CoA …ATP

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20
Q

What is DNP? What does it do?

A

Dinitrophenol (DNP)
*acts as an uncoupling agent: protons that are pumped out of the mito matrix by the ETC are carried back in by DNP and therefore do not pass through ATP synthase.

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21
Q

How can you lose weight with DNP?

A

the body doesn’t get enough ATP and so it keeps using fuel. Heat is a byproduct of the protons being shuttled back and forth by DNP

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22
Q

What are Ketone Bodies?

A

*Produced in liver from substrate Acetyl CoA

Acetyl CoA was produced by B-Oxidation from FAs

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23
Q

3 ketone bodies:

A

Acetoacetate
B-hydroxybutyrate
Acetone

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24
Q

Which tissues use Ketone Bodies?

A

Cardiomyocytes

Skeletal Muscles

Brain (ONLY during starvation)

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25
In order to use ketone bodies for fuel, which must tissues have?
Must have enzyme to convert Acetoacetate back to Acetyl CoA
26
Pancreatic Islets are made of ...
alpha cells: secrete glucagon beta cells (majority): secrete insulin
27
Which nutrients in the blood will stimulate the release of insulin?
* Glucose * Amino acids * Fatty acids * Other hormones
28
What does insulin promote?
Promotes the storage of surplus fuel
29
What processes will Insulin suppress?
gluconeogenesis (formation of glucose from non-carb substrates) glycogenolysis (formation of glucose from glycogen)
30
Which hormones allow us to use stored energy reserves and mobilize fuel in times of fasting or “famine”?
RELEASED SOON: Glucagon Epinephrine/norepinephrine RELEASED LATER: Cortisol Growth Hormone
31
What does Glucagon do?
Mobilization of fuel from liver & adipose tissue Promotes breakdown of glycogen to glucose AND TAGs to FAs & glycerol
32
Where is Epinephrine released from?
Adrenal Medulla
33
What does Epinephrine target?
liver adipose tissue skeletal muscle
34
When is Epinephrine released?
Released when blood glucose levels are low | "Fight or Flight"
35
How is Epinephrine produced?
Derived from Tyrosine
36
Where is Coritsol released from?
Adrenal Cortex
37
How is Cortisol produced?
derivative of Cholesterol
38
When is Cortisol released?
prolonged fast
39
Where is GH released from?
Produced and secreted from somatotrophes of the anterior pituitary
40
When is GH released?
During prolonged fast
41
What does GH do?
Raises blood glucose levels | Promotes protein synthesis
42
What is the LONG-TERM consequence of poorly managed diabetes?
* High blood glucose causes tissue damage (nerve cells and blood vessels) * Cardiovascular Disease due to high lipid levels
43
What is the SEVERE-ACUTE consequence of poorly managed diabetes?
Diabetic ketoacidosis: Severe hyperglycemia, counter regulatory hormones break down TAGs ... big release of Ketones ... Acidosis / dehydration ... LOC ... death
44
Where is Leptin produced?
Produced & secreted by Fat Cells
45
What is the function of Leptin?
To communicate from the periphery to the brain of fuel storage status Leptin tells the brain to: (1) Decrease food intake (2) Increase energy expenditure
46
How can Leptin be used to treat obesity?
Only in obesity caused by Leptin def since the patient would be very sensitive to Leptin DOES NOT work for most of the obese population because they have Leptin resistance
47
What is the effect of low levels of Leptin
Tells the Hypothalamus to take in more food
48
In the absence of O2, how can glycolysis continue?
replenish NAD+ by having NADH reduce pyruvate to become lactate
49
What is the first line of fuel upon initiation of explosive contraction in exercise?
ATP & Creatine Creatine-P + ADP ...yields ... Creatine & ATP
50
What is used as fuel when the body is at rest?
FAs
51
What is the progression of fuels sources in LOW to MODERATE exercise
INTIALLY: *intramuscular Glycogen THEN: * Blood glucose * intramuscular FA FINALLY: *FAs from Liver & Adipocytes
52
What stored fuel source do Type 1 muscle fibres use?
Type 1 = Slow Twitch | TAGs
53
What stored fuel source do Type 2a muscle fibres use?
Type 2a = Fast Twitch | Glycogen, TAGs
54
What stored fuel source do Type 2x/b muscle fibres use?
Type 2x/b = Fast Twitch | ATP, Creatine Phosphate (CP)
55
What is the Anaerobic Alactic System?
During initial explosive contractions, spent ATP is immediately replenished by the Creatine Phosphate which stores some P reading to be react with ADP. Does NOT result in the production of lactic acid (ATP begins to be produced through catabolism of fuels as CP levels start to decline)
56
High Intensity VS Low Intensity Exercise Which fuel sources predominate?
HIGH INT: carbs LOW INT: fat
57
McArdle’s Syndrome
Glycogen Storage Disease | **There is no enzyme Glycogen Phosphorylase to breakdown glycogen into glucose
58
What is the body's priority during exercise?
Protect Muscle Glycogen Protect Blood Glucose (But...muscle glycogen will be sacrificed first)
59
What hormone do we NOT want around during exercise?
Insulin ... we want to use energy, not store it!
60
Which tissues can use lactate as fuel?
aerobic slow twitch skeletal muscle and cardiac muscle
61
What is Lactic Acidosis?
occurs when there is an excess accumulation of lactic acid/lactate
62
What is the metabolic result of convulsions? | extreme exercise, contractions
causes Lactic Acidosis which should then dissipate once the seizures have stopped
63
What is the effect of Cyanide?
Cyanide poisons the respiratory chain Causes lactic acidisos by increasing lactate production and decreasing consumption
64
What is the role of Vit B1
THIAMIN cofactor for pyruvate dehydrogenase (without it, pyruvate cannot be converted to acetyl CoA ... leads to acid acidosis)
65
"shoshin beriberi"
severe form of acute thiamin deficiency | Japan-1920s
66
2 main types of starvation
marasmus (cal def) kwashiorkor (protein def)
67
What are the body's top 2 priorities during starvation?
(1) Protect blood glucose level | (2) Protect proteins
68
How long does glycogen stores last?
supplies last 1 day
69
What happens after half a day of starvation?
reduction in blood glucose and in insulin promotes an increased rate of liver gluconeogensis glyercol & aa are converted to glucose
70
What happens after a full day of starvation?
body shifts to depend more on fat and less on protein for fuel The liver increases its rate of converting fatty acids to ketones.
71
What happens after abot 3 days of starvation?
brain starts producing the enzymes necessary to convert Ketone bodies to acetyl CoA (reduces need to use proteins)
72
What actually kills a starving person?
excessive destruction of body proteins, infection NOT low glucose levels
73
What happens to ethanol?
(1) reduced by NAD+ to Acetaldehyde (Alcohol Dehydrogenase) (2) reduced again by NAD+ to Acetate (Aldehyde Dehydrogenase) (3) converted to Acetyl CoA
74
How can ethanol react with some drugs?
Ethanol can be oxidized to acetaldehyde by a hepatic “microsomal mixed function oxidase”, which uses a cytochrome P450 Some medications are metabolized by P450 and therefore are not broken down properly if ethanol is competing against it for P450.
75
What causes the nausea, face flushing, and headache associated with high alcohol consumption?
Accumulation of Acetaldehyde - makes you feel like crap
76
What happens when the body is overwhelmed by alcohol?
breaking down alcohol uses up all of the NAD+ and there are no more left to perform the CAC Acetyl CoA is instead converted to a lot of ketones. Results in Acute Ketoacidosis.
77
What is the ACUTE effect of alcohol over-consumption?
Ketoacidosis | Since CAC is blocked by not enough NAD+, pyruvate is forced to be converted to Ketones ... LOTS of ketones!
78
What is the CHRONIC effect of alcohol over-consumption?
Fatty Liver alcohol gets converted to TAGs and stored in liver (1) Excess fatty acids are converted to TAGs because B-oxidation of FAs is slowed by the high NADH/NAD+ ratio, (2) the liver’s ability to export lipids is reduced by alcohol ... TAG is stored ... fatty liver.
79
How does the body try and fix the high NADH/NAD+ ratio?
regenerate NAD+ by converting pyruvate to lactate which builds up. Regenerated NAD+ gets used for more alchohol breakdown, NOT CAC!
80
Under what conditions can Ethanol Promote Hypoglycemia?
(1) Blood sugar already low (2) Alcohol inihibits gluconeogenesis CHILDREN are particularly at risk as they have low glycogen stores (and malnourished adults)
81
How can we treat chronic alcoholism?
Disulfiram | causes a buildup of Acetaldehyde which makes you feel like crap and acts as a deterrent.
82
Why fruity breath in a hypoglycemic?
Acetone (1 of 3 ketone bodies) Ketones are broken down to maintain energy levels
83
Why give Thiamin when administering Dextrose?
to prevent Wernicke-Korsakoff Syndrome
84
What hormone activity do we expect in a normal healthy person who has acute hypoglycemia?
LOW Insulin HIGH Glucagon HIGH Epinephrine this combination results in the production of ketone bodies. WE SHOULD SEE KETONE LEVELS ELEVATED
85
What is the effect of insulin overdose on ketone production?
Overdose of Insulin will overpower / inhibit the activity of hormones including epinephrine & glucagon. Therefore, ketone levels will be low. (this is Gary's case)
86
What is the C-Peptide test?
Test to identify source of Insulin in system is exogenous or endogenous. If endogenous ... then suggests tumor If exogenous ... then insulin OD
87
Where does beta oxidation of fatty acids take place?
In the mitochondria of many tissues
88
During a marathon, the majority of the ATP utilized by skeletal muscle comes from:
Fatty acid and glucose oxidation
89
After 3-4 days of fasting, what happens to the rate of gluconeogenesis?
decreases
90
Survival time during starvation is primarily a function of:
the amount of fat available
91
What is latanaprost?
PGF2-alpha analogue | reduces intraocular pressure
92
Where are ketone bodies produced?
Ketone bodies are produced by the liver used by cardiomyocytes and a few other cell types.
93
In aerobic conditions, how do the pathways for glucose metabolism and fatty acid metabolism converge?
Acetyl CoA
94
When insulin levels are low, glucose transport across the cell membranes of ________ is inhibited ?
Adipose Tissue Cells
95
Where does beta oxidation of fatty acids take place?
In the mitochondria of many tissues
96
Timeline of Energy Sources During Starvation
After half a day: Glucose used up After 24 hours: Glycogen stores depleted Gluconeogenesis begins Day 3: Ketone Synthesis Begins Gluconeogenesis decreases After Several Weeks: Ketone Synthesis Stops Gluconeogenesis increases and continues until sufficient proteins are catabolized to cause death
97
Which organs make ketones?
ONLY the LIVER!!!!

PRIN (13 decks)

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