Lecture 33

Question 1

State the 3 metabolism molecules where the cell makes “a decision”.

Answer 1

1. Glucose-6-phosphate:
2. Pyruvate:
3. Acetyl-CoA

Question 2

For Glucose-6-phosphate, explain the 2 available “decisions” the cell can make in terms of where to go with metabolism from here.

Answer 2

glucose-6-phosphate:
1. Enter glycolysis and become Fructose-6-phosphate

2. Enter gluconeogenesis and become Glucose-1-phosphate

Question 3

For Pyruvate, explain the 4 available “decisions” the cell can make in terms of where to go with metabolism from here.

Answer 3

Pyruvate:
1. Enter TCA cycle (to make energy) and become Acetyl-CoA

2. Enter Fermentation (to make less energy) and become Lactate
3. Enter Gluconeogenesis and become OAA
4. Enter AA synthesis and become Alanine

Question 4

For Acetyl-CoA, explain the 3 available “decisions” the cell can make in terms of where to go with metabolism from here.

Answer 4

Acetyl-CoA:
1. Enter TCA cycle and Ox-Phos and become CO2 + H2O

2. Enter Ketone body Synthesis and become a ketone (Acetoacetate, Acetone, or Beta-Hydroxybutyrate)
3. Enter FA synthesis and become a FA (TAG)

Question 5

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

Liver

Answer 5

Fuel reserves: TAGs and Glycogen

Pathways: 
Glycolysis
Gluconeogenesis
Beta-oxidation
FA synthesis

Question 6

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

Muscle

Answer 6

Fuel Reserves: Glycogen and Protein

Pathways: 
Beta-oxidation
Glycolysis
Proteolysis
TCA cycle

Question 7

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

GI (intestines)

Answer 7

Fuel Reserves: none

Pathways: none

Question 8

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

Brain

Answer 8

Fuel Reserves: none

Pathways:
Glycolysis
TCA cycle

Question 9

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

Heart

Answer 9

Fuel Reserves: none

Pathways:
Beta-oxidation
TCA cycle

Question 10

Describe what the following organ does in terms of fuel reserves it may have and energy pathways it may conduct.

Adipose tissue

Answer 10

Fuel Reserves: TAGs

Pathways:
Beta-oxidation
TAG synthesis

Question 11

State the 3 tissues that store energy molecules and the 3 that make energy molecules

Answer 11

Store energy molecules:
Skeletal Muscle (at rest), Adipose, and Liver

Make energy molecules:
Skeletal Muscle (during exercise), Adipose, and Liver

Question 12

For Brain tissue, state its
Fuel Reserves:
Preferred Fuel: (include it normally and during starvation)
Fuel sources exported:

Answer 12

Fuel Reserves: none

Preferred Fuel: Glucose (ketone bodies during starvation)

Fuel sources exported: none

Question 13

For Skeletal Muscle tissue at rest, state its
Fuel Reserves:
Preferred Fuel:
Fuel sources exported:

Answer 13

Fuel Reserves: Glycogen and Protein

Preferred Fuel: FAs

Fuel sources exported: none

Question 14

For Skeletal Muscle tissue during exercise, state its
Fuel Reserves:
Preferred Fuel:
Fuel sources exported:

Answer 14

Fuel Reserves: none

Preferred Fuel: glucose

Fuel sources exported: Lactate

Question 15

For Heart Muscle tissue, state its
Fuel Reserves:
Preferred Fuel:
Fuel sources exported:

Answer 15

Fuel Reserves: none

Preferred Fuel: FAs

Fuel sources exported: None

Question 16

For Adipose tissue, state its
Fuel Reserves:
Preferred Fuel:
Fuel sources exported:

Answer 16

Fuel Reserves: TAGs

Preferred Fuel: FAs

Fuel sources exported: FAs (TAGs) and Glycerol

Question 17

For Liver tissue, state its
Fuel Reserves:
Preferred Fuel:
Fuel sources exported:

Answer 17

Fuel Reserves: TAGs and Glycogen

Preferred Fuel: Glucose, FAs, or AAs

Fuel sources exported: FAs, Glucose, and Ketone Bodies

Question 18

State the fuel that is produced by these 3 fuel producers of the body.

Liver:
Adipocytes:
Kidney:

Answer 18

Liver: Glucose

Adipocytes: FAs

Kidney: Glucose (during starvation only)

Question 19

State the fuel molecules in order of most preferred to least preferred for the following tissues.

Skeletal Muscle:
Brain:
Heart:

Answer 19

Skeletal Muscle: Glycogen then Creatine Phosphate then Lactate

Brain: Glucose then Ketone bodies

Heart: FAs then Lactate/Ketone bodies

Question 20

True or False:

The Primary fuel for Liver tissue is Glucose. explain.

Answer 20

False.

The primary fuel for Liver tissue is FAs, however it can use Glucose or even AA’s if it needs to

Question 21

Explain how fed and fasting states affect the reaction rate of glucokinase in in the liver and what the liver is synthesizing.

Answer 21

Fed State: increases the glucokinase reaction rate
FA’s (TAGs) are synthesized

Fasting State: decreases the glucokinase reaction rate
Ketone Bodies are synthesized

Question 22

Glucokinase, and enzyme only found in the liver and kidneys, has a _____Km value than Hexokinase which is found in the liver, kidneys and even muscle tissues. Explain what this difference in Km value means.

Answer 22

Higher

Since Glucokinase has a higher Km value, it takes a very large amount of glucose in the liver to reach the Vmax of glucokinase, whereas Hexokinase is almost always at it’s Vmax bc it takes small levels of glucose to reach it.

Question 23

True or False:

The liver can produce Ketone Bodies but is unable to use them as fuel. explain.

Answer 23

True:

It can make Ketone bodies from AA’s but it LACKS CoA Transferase, so it is unable to make Acetyl-CoA from Ketone bodies (therefore it cannot use Ketone bodies as fuel)

Question 24

State the 2 enzymes that are unique to the Liver and Kidneys only.

Answer 24

glucose-6-phosphatase (allows them to “complete” gluconeogenesis)

Urea Cycle Enzymes

Question 25

Describe the effect that Etoh consumption has on NAD+ levels. What pathways are affected by these low levels of NAD+ that can occur from Etoh consumption?

Answer 25

Etoh consumption decreases NAD+ levels ``` This decreases the activity of the following pathways Gluconeogenesis Glycolysis TCA cycle Beta-oxidation ```

Question 26

An increase in what 2 molecules is responsible for your hangover after drinking Etoh?

Answer 26

increased lactate and Ketone bodies (causing acidosis)

Question 27

State the time it takes to achieve the following metabolic states and the main mechanism/goal of each state Fed: Fasting: Starvation:

Answer 27

Fed: begins at the conclusion of a meal Energy production and storage Fasting: begins 1 hr after a meal uses PREFERRED metabolic fuel stores to provide energy (like making glucose from glycogen) Starvation: begins around 4-5 days without food intake uses fat stores (TAGs) and Derivatives (Ketone Bodies) to provide energy

Question 28

For the following cholesterol-containing molecules, state the origin, destination, and function of it. Chylomicrons

Answer 28

Chylomicrons Origin: Intestine (basically come straight from food) Destination: Adipocytes Function: TAG transport

Question 29

For the following cholesterol-containing molecules, state the origin, destination, and function of it. VLDLs

Answer 29

VLDLs Origin: Liver Destination: Adipocytes Function: TAG transport

Question 30

For the following cholesterol-containing molecules, state the origin, destination, and function of it. IDLs

Answer 30

IDLs Origin: VLDL's Destination: Liver and Adipocytes Function: Intermediate molecule

Question 31

For the following cholesterol-containing molecules, state the origin, destination, and function of it. LDLs

Answer 31

LDLs Origin: VLDLs Destination: All cells Function: Cholesterol Distribution

Question 32

For the following cholesterol-containing molecules, state the origin, destination, and function of it. HDLs

Answer 32

HDL Origin: Liver (empty when they leave) Destination: Liver (full when they return) Function: Cholesterol Collection

Question 33

Explain how IDLs and LDLs are created from VLDLs

Answer 33

VLDLs are purged (TAGs are removed from them) until they form IDLs and can eventually form LDLs after more purging past the IDL stage

Question 34

Compare LDLs with HDLs in terms of "good and bad" and the protein to cholesterol composition of them

Answer 34

HDLs are the "good cholesterol" with more protein and less cholesterol in them (these will circulate and "fill up" with excess cholesterol and return it to the liver) LDLs are the "bad cholesterol" with less protein and more cholesterol composing them (these circulate and deposit cholesterol throughout the body)

Question 35

What type of metabolic condition does diabetes mimic? explain how.

Answer 35

Diabetes mimics starvation conditions because during both diabetes and starvation, glucose cannot be used to provide the body with energy (in starvation it is bc there is not glucose around to be used) (indiabetes its bc insulin issues do NOT bring glucose into the cell)

Question 36

State the 3 enzymes that are considered master regulator molecules of metabolism. Then state the 7 Hormones that are considered master regulator molecules of metabolism

Answer 36

Enzymes: "SAM" mnemonic Sirtuins AMPK mTOR ``` Hormones: "I Get Lost PAGE" Insulin Glucagon Leptin PYY3-36 Adiponectin Ghrelin Epinephrine ```

Question 37

State 2 Serine/Threonine kinases with opposite functions that regulate metabolism. Which of these is active in the fed state and which is inactive in the fed state?

Answer 37

AMPK and mTOR mTOR is active in the fed state (bc it triggers anabolic activity) AMPK is inactive in the fed state (bc it triggers catabolic activity)

Question 38

For AMPK and mTOR, state what molecules activate and inhibit each of them.

Answer 38

AMPK: Increased AMP activates it Increased ATP Inhibits it mTOR: Insulin activates it AMPK (on) Inhibits it

Question 39

AMPK is a heterotrimeric protein. State the 3 subunits that compose AMPK and give their functions (one of the subunits serves 2 functions)

Answer 39

Alpha: N-terminus is the active site with a kinase domain C-terminus is the regulatory site that is phosphorylated when the protein is "activated" Beta: structural component Gamma: Binds 4 AMPS

Question 40

How are AMPK and PPAR (Peroxisome Proliferator-Activated Receptor) related? Describe the function of PPAR

Answer 40

Activated AMPK activates PPAR PPAR has 4 isozymes that serve slightly different purposes in different tissues but all of them regulate metabolism of FAs and lipid synthesis

Question 41

State what the following hormones signal Insulin: Glucagon: Epinephrine:

Answer 41

Insulin: Signals fed state Glucagon: Signals fasting state Epinephrine: Signals stress

Question 42

Leptin and Insulin work together in order to determine what? Compare the 2 in terms of what releases them, what type of sensor they serve as, and what they "signal" in terms of metabolic states.

Answer 42

They work together to determine what molecules are available to be used for energy Insulin: Released from Pancreas Blood glucose sensor Actions signal fed state Leptin: Released from Adipocytes TAG storage sensor Actions signal full state

Question 43

State 2 hormones that signal the full state, much like leptin, but their action is much more brief than leptin. Why is their action so much shorter?

Answer 43

CCK (Cholecystokinin) and GLP1 (Glucagon-like peptide 1) Their action is shorter than leptin because they are peptide hormones (short duration of action by nature)

Question 44

State the 3 hormones that activate Anorexigenic neurons and state what occurs when these neurons are stimulated. Do the same for the 2 hormones that stimulate Orexigenic neurons.

Answer 44

``` Anorexigenic neurons: signal fed/full state when stimulated 1. Leptin 2. Insulin 3. PYY3-36 ("LIP" mnemonic) ``` Orexigenic neurons: signal "hungry" state when stimulated 1. Ghrelin 2. Adiponectin

Question 45

True or False: | Cortisol is a fast-acting hormone that is derived from cholesterol. explain.

Answer 45

False Cortisol is not a fast acting hormone (most cholesterol derived hormones are not fast acting) Cortisol is a SLOW-acting hormone that is derived from cholesterol

Question 46

State the effect that cortisol has on the following tissues. Adipocytes: Skeletal Muscle: Liver:

Answer 46

Adipocytes: release FAs Skeletal Muscle: Protein degradation and export AAs Liver: Increase in pyruvate carboxylase, leading to an increase in gluconeogenesis