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BioMedChem Midterm 1 > 6 - Metabolic stress in Cancer, Starvation, Exercise > Flashcards

6 - Metabolic stress in Cancer, Starvation, Exercise Flashcards

1
Q

Postabsorptive Phase 1

A
  • Glucose Maintained
  • Insulin Decreased
  • Liver:
    • Glycogenolysis
      • Glycogen -> Glucose
    • Gluconeogenesis
  • Glucose Oxidation for ATP Generation
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2
Q

Fasting Phase 2

A
  • Decreased Glucose & Insulin
  • Increase in KETOACIDS
  • Stored TG’s -> FA’s
    • ​after depletion of hepatic glycogen
  • Reliance on LIPID oxidation for ATP generation
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3
Q

Starvation Phase 3

A
  • Greatly reduced Glucose + Insulin
  • Greatly increased KETOACIDS
  • depletion of LIPID storage
  • Reliance on LEAN TISSUE & PROTEIN catabolism
    • ​Protein -> AA’s -> Glucose
      • for ATP generation
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4
Q

Ketogenic Diet

A
  • High PROTEIN diet
    • low carbohydrate supply
  • ​Normally Glycogen > TG’s > Protein
    • Since there is a low Glycogen supply, Body thinkgs it is “Starving”
      • Body will liberate TG’s first from adipocytes
        • ​and produce ketones
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5
Q

Normal Ghrelin Function Pathway

A
  • Ghrelin signaled to release from STOMACH
    • ​-> Hypothalmus NPY signals HUNGER
      • AgRP also increased
      • POMC decreased
        • ​-> Medulla oblongata = Reticular Formation
          • ​Somatic: Increase Feeding
          • Sympathetic : Reduce Metabolism
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6
Q

When feeding Ghrelin is?

A
  • SUPPRESSED
  • ​​Leptin from adipocytes -> Hypothalmus
    • inhibits NPY gene expression in Arcuate Nucleus
    • also reduces AgRP
    • increases POMC
      • ​ Tells You it’s Full = SATIETY
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7
Q

Ghrelin in STARVATION

A
  • Starvation & Weight loss:
    • INCREASES GHRELIN LEVELS
      • then return to normal upon feeding
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8
Q

Ghrelin levels are ____ in bulimia nervosa patients

A

HIGHER

Body is telling you you should eat

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9
Q

​Ghrelin levels are ____ in OBESE individuals

A

Lower

Body is telling you to stop eating

But in obese individuals w/ WEIGHT LOSS:

Ghrelin levels will INCREASE

Telling you should eat more, but you have to try and IGNORE

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10
Q

Autophagy

A

Intracellular LYSOSOMAL degradation & recycling of proteins

  • Regulated through ATG (autophagy related genes) by
    • mTOR inhibits
    • AMPK & Nutrient availability
  • ​ATG protein + Membrane = Autophagosome
    • Autophagosome + Lysosome = Autophagolysosome
      • provides Hydrolases to degrade cargo
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11
Q

ATG

A

Autophagy Related Genes

Used to regulate Autophagy through:

AMPK + Nutrient Availability

Inhibited by mTOR

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12
Q

Autophagosome

A

Double Membrane Vescicle that captures cytoplasmic cargo

ATG Proteins + Membrane

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13
Q

Autophagolysosome

A

Provides Hydrolases to degrade cargo in Autophagy

Autophagosome + Lysosome

Recycles AA’s / Nucleosides / FA’s / Sugars for:

Metabolism / Redox / Energy / Biomass

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14
Q

Autophagy Pathway in Nutrient RICH conditions:

A
  • AA’s -> Activate mTORC1
    • ​P6K + 4EBP1
      • -> protein translation + Cell Growth
    • DAP1
      • ​INHIBITS AUTOPHAGY
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15
Q

Autophagy in Starvation Conditions

A
  • LKB1 senses low energy
    • ​activates AMPK
      • -> inactivates mTORC1 through TSC
        • ​*rapamycin also inhibits mTORC1
      • ​​​​DAP1 is no longer inhibiting autophagy
        • ​AUTOPHAGY OCCURS
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16
Q

How does AUTOPHAGY help starvation?

A
  • Autophagy liberates material that can generate energy through the TCA Cycle
    • ​​​Studies showed that autophagy is necessary for more energy through TCA
  • Autophagy generated nutrients can be EXPORTED
    • –> to help OTHER cells.
    • Without Autophagy starvation is MORE severe
      • intracellular AA drop
      • block protein synthesis
17
Q

Fatty Acid Uptake in STARVATION

A
  • Fasting causes:
    • INCREASES in FATTY ACID UPTAKE TRANSPORTERS in the Muscle
      • Decreases the FA transporters in the Liver & Adipose
  • ​​​Uptake of FFAs in muscle helps maintain FFA in circulation
18
Q

Agouti-Related Peptide

AgRP

A
  • AgRP neurons in the Hypothalmic Arcuate Nucleus
    • focal point for nutritional & metabolic cues
      • ​remember Leptin material
  • Autophagy is key for regulating food intake through AgRP hypothalmic expression
19
Q

FFA are _____ in Starvation and leads to?

A
  • FFA INCREASES in starvation
    • -> Hypothalmic FFA Uptake
      • -> Promotes AUTOPHAGY​​
20
Q

Reduction of Autophagy in hypothalmus causes?

A
  • Reduces AgRP
    • ​Food Intake
    • Adiposity
  • Autophagy is KEY for regulating food intake through AgRP hypothamic expression
    • _​_Without Autophagy, AgRP does not stimulate an increase in food intake
21
Q

AgRP Neurons are STIMULATED by what?

A

Active AgRP –> Increase food intake

  • Ghrelin
  • Fatty Acids​
  • Glucose
  • Starvation​/ Autophagy
    • ​-> Increase in FFA
      • -> Become TG’s
        • -> Lipid Droplets -> Autophagy
22
Q

AgRP is downregulated by which hormones?

A

Decrease in AgRP -> Satiety / less food intake

LEPTIN

AgRP remembers leptin material

23
Q

How does the LIVER work with Exercise?

A
  • Without energy stores in Liver exercise is not possible
    • liver meets energy demands of the muscle
  • Exercise -> Starvation mode
    • Liver is out of glycogen -> glucose
      • ​Increased OXIDATION of FFA from adipose
        • ​FFA supply energy to liver
          • FFA->Acetyl-CoA -> Krebs
24
Q

Exercise leads to an INCREASED need for?

A

Glucose / Lipids / Glycogen in the muscle__​

Some amino acids

  • Glucose comes from the liver, which consumes ATP
    • -> Energy Charge decreases (less ATP avail)
    • pushes cell into:
      • Gluconeogenesis / Fatty Acid Oxidation
      • Enhanced Activation of AMPK
25
Q

How does EC change with exercise?

A
  • Liver’s (Hepatic) Energy charge DECREASES
    • ​–> in turn activates AMPK in liver
  • Muscle EC does not change
26
Q

AMPK changes with exercise

A
  • Hepatic EC decreases
    • Increase in hepatic p-AMPK​
  • In other organs outside of liver there is:
    • Increase in FA Oxidation
    • Increase in Gluconeogenic Drive
27
Q

High Energy Charge does what to Catabolic pathways?

A
  • High EC
    • -> Inhibits Catabolic Pathways (generate energy)
      • Inhibits AMPK
28
Q

High Energy Charge does what to Anabolic pathways?

A
  • low EC:
    • ​-> Increase in Anabolic Pathways (energy utilizing)
29
Q

Exercise Increases Gluconeogenesis in which Organs?

A

​All nutrients go to LIVER to be converted to Glucose

Exercise also accelerates the

DELIVERY & EXTRACTION of glucose

  • Gut
    • ​AA / Pyruvate + Lactate
  • Muscle
    • ​Pyruvate + Lactate
  • Adipose
    • Glycerol
30
Q

How does exercise affect GLUCAGON?

A
  • Exercise -> Increased Glucagon secretion & effectiveness
    • _​_tells liver to create more Glucose
      • ​to feed the muscle
        • _​_to prevent HYPERglycemia
  • Prolonged Exercise -> Decreased Insulin
31
Q

How does exercise INCREASE Insulin sensistivity?

A
  • Acute Exercise increases effectiveness in:
    • Insulin’s ability to transport glucose
    • ​​Increased activity of insulin receptor
      • ​More GLUT4 receptors
        • to bring bring glucose into cells
    • Decreased muscle glycogen concentration
32
Q

Women’s Differences in metabolism

A
  • Women have more:
    • % body fat
    • subcutaneous fat (SC)
  • ​Women have less:
    • ​Viceral Fat
    • muscle mass
    • oxidize less lipid substrate
33
Q

Exercise role with T2DM

A
  • Can DELAY or PREVENT T2DM
  • Improve:
    • Blood Glucose
    • Body Weight
    • Lipids
    • Blood Pressure

BioMedChem Midterm 1 (9 decks)

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