Mammalian Fuel Metabolism

Question 1

Specialization of metabolism in the brain

Answer 1

-high respiration rate
-energy is used to power ATPase that maintains the membrane potential in neurons
-the brain stores very little glycogen so it requires a steady glucose supply

Question 2

Specialization of metabolism in muscle

Answer 2

storage: glucose is stored as glycogen because it can be broken down quickly.

fasting: glycogen is consumed quickly so fatty acids and ketone bodies are used when glycogen is depleted

Muscle stores ATP as phosphocreatine which is used to replace ATP when its depleted

Anaerobic glycolysis takes over and produces lactate

Eventually oxidative phosphorylation is used to maintain ATP production

Question 3

Specialization of metabolism in adipose tissue

Answer 3

storage: adipocytes convert free fatty acids to triacylglycrol for energy storage. glycerol is produced from glucose vi DHAP

fasting: adipocytes release FFAs from TAG and export them to the blood. absence of new glycerol drives this process

Question 4

Adiponectin

Answer 4

produced by adipocytes but production is decreased if there’s too much adipose tissue
binds receptors on muscle and liver cells which stimulates the AMPK pathway, inhibiting gluconeogenesis, and stimulates FA uptake and oxidation

Question 5

Leptin

Answer 5

produced by fat cells to control appetite and body weight

production increases with increased adipose tissue, but the receptor or transports across BBB may be deficient in obese people

Question 6

Neuropeptide Y

Answer 6

produced by hypothalamus, stimulates appetite
leptin and insulin prevent secretion

Question 7

Human ghrelin

Answer 7

stimulates appetite by increasing NPY levels
secreted by empty stomach

Question 8

Human PYY

Answer 8

-decreases appetite by inhibiting NPY
-secreted from GI tract

Question 9

Glucokinase

Answer 9

not inhibited by its product (G6P) and is active in high glucose concentrations (high Km)
It allows the liver to take up excess glucose but doesn’t compete with other organs at low blood glucose

Question 10

4 fates of G6P in the liver

Answer 10

1. converted to glucose for secretion
2. converted to glycogen for storage
3. converted to acetyl-coa for lipid biosynthesis
4. generate ribose-5-phosphate and NADPH via PPP

Question 11

Cori cycle

Answer 11

purpose: recycle lactate

steps:
1. lactate travels to liver from muscle via blood
2. lactate dehydrogenase converts to pyruvate
3. converted to acetyl-coa for lipid biosynthesis
4. new glucose secreted to replenish muscle tissue

Question 12

Glucose-alanine cycle

Answer 12

Purpose: circulates pyruvate during fasting to produce NH3 and glucose

steps:
1. pyruvate converted to alanine which then travels from muscles to liver
2. amino group transferred to a-ketoglutarate, generating glu
3. Glu releases amino groups as NH3
4. Ala converted to pyruvate and glucose
5. Glucose secreted

Question 13

Insulin is secreted by _____ in response to high blood glucose levels

Answer 13

pancreatic b-cells

Question 14

How is glucose uptake in muscle and adipocytes regulated

Answer 14

it’s regulated by insulin through controlling GLUT4 exocytosis

Question 15

GLUT4

Answer 15

normally in membrane vesicles but insulin stimulates vesicle localization with the plasma membrane for glucose uptake

Question 16

Does the brain’s rate of glucose uptake rely on insulin

Answer 16

No

Question 17

What affect does insulin have on the liver

Answer 17

liver represses gluconeogenesis to store glucose

Question 18

AMP-Dependent-Protein Kinase (AMPK)

Answer 18

-intracellular kinase that responds to the AMP/ATP ratio
AMP allosterically activates while ATP allosterically inhibits

Question 19

AMPK activates

Answer 19

PRK2/FBPase- increased glycolysis
GLUT4 exocytosis- increased glucose uptake in the muscle
FA Oxidation- decreasing malonyl-coa via acetyl-coa decarboxylase inhibition

Question 20

AMPK inhibits

Answer 20

acetyl-coa decarboylase
glycogen synthase

Question 21

Starvation

Answer 21

12 hours
-increased glucagon leads to FA mobilization and skeletal muscles consume
-glucose is saved for the brain because it cannot used FAs

40 hours
-liver gluconeogenesis supplies 95% of glucose
- carbon comes from TAG and glucogenic amino acids

> 48 hours
-acetyl-coa accumulation from FA oxidation
-ketone body synthesis in liver, brain adapts
-rate of skeletal muscle breakdown decreases
-brain glucose demand drops

Question 22

Metabolic changes in cancer cells

Answer 22

-increased glycolysis
-protein/nucleotide biosynthesis initiated form glycolytic intermedia buildup
-glutamine utilization from blood increases
-blood vessel growth due to increased lactate secretion

Question 23

Type 1 Diabetes

Answer 23

-insulin dependent
-caused by pancreatic b-cell deficiency and failure to produce insulin
-autoimmune disease b/c the body attacks pancreatic b-cells
problems arise from hyperglycemia and uncontrolled metabolic responses

Question 24

Type 2 diabetes

Answer 24

-not insulin dependent
-organs are insulin resistant

Question 25

Type 1 diabetes treatment

Answer 25

insulin injections

Question 26

Type 2 diabetes treatment

Answer 26

-Metformin- decreases glucose release by liver, increased AMPK activity
-TZD promotes insulin-stimulated glucose disposal in muscle, alters AMP/ATP ratio to indirectly stimulate AMPK