L13: PPP, Glycogen Metabolism, and Alcohol Metabolism

Question 1

main functions of pentose phosphate pathway

Answer 1

• bypass first step in glycolysis
• generate NADPH
• generate ribulose-5-phosphate
• provide precursors for nucleotide biosynthesis

Question 2

NADPH role

Answer 2

• reductive reactions required for biosynthesis
• protection against oxidative stress
• fatty acid synthesis
• glutathione reduction

Question 3

ribulose-5-phosphate role

Answer 3

• nucleotide biosynthesis

Question 4

oxidative phase

Answer 4

• oxidation of glucose-6-phosphate to ribulose-5-phosphate
• via glucose-6-phosphate dehydrogenase
• produces 2 NADPH

Question 5

non-oxidative phase

Answer 5

• ribulose-5-phosphate to fructose-6-phosphate

- produces glycolytic pathway intermediates

Question 6

Phase I regulation of PPP

Answer 6

• high NADPH inhibits glucose-6-phosphate dehydrogenease

Question 7

Phase II regulation of PPP

Answer 7

• controlled by substrate availability

Question 8

cancer cells and PPP

Answer 8

• need nucleotides for DNA and RNA synthesis
  
  • so need ribose-5-phosphate
• need NADPH for fatty acid synthesis

Question 9

Why do we use glycogen for storage?

Answer 9

• glucose cannot be stored by itself because it would disrupt the osmotic balance of the cell

Question 10

alpha 1,4 linkage in glycogen

Answer 10

• joins the glucose molecules in a linear molcule

Question 11

alpha 1,6 linkage in glycogen

Answer 11

• results in branches

Question 12

why do we have branches in glycogen?

Answer 12

• makes it much easier for enzymes involved in degradation to find something to degrade

Question 13

function of glycogen in the muscle

Answer 13

• serves as a fuel source

Question 14

function of glycogen in the liver

Answer 14

• serves as a good source of blood glucose for other tissues

Question 15

energy requirements in glycogen synthesis versus breakdown

Answer 15

• synthesis requires energy

- breakdown does not

Question 16

glycogenolysis step 1

Answer 16

• via phosphorylated glycogen phosphorylase
• cleaves alpha 1,4 bonds, adds a phosphate
• releases glucose-1-phosphate residues until only 4 residues remain

Question 17

glycogenolysis step 2

Answer 17

• transferase removes outer 3 glucose residues from a branch and transfers them to another chain

Question 18

glycogenolysis step 3

Answer 18

• alpha-1,6-glucosidase (branching enzyme) cleaves alpha-1,6 bond on the single residue

Question 19

glycogenolysis step 4

Answer 19

• glucose-1-phosphate converted to glucose-6-phosphate by phosphoglucomutase

Question 20

liver versus muscle in glucose-6-phosphatase

Answer 20

• liver breaks down glucose-6-phosphate to glucose via glucose-6-phosphatase in ER membrane
• muscle uses glucose-6-phosphate to generate ATP
  
  • does not have phosphatase

Question 21

important component of glycogen degradation

Answer 21

• glycogen phosphorylase

Question 22

hormones that control glycogen degradation

Answer 22

• glucagon in the liver
• epinephrine in the muscle
• signal through GCPR pathway

Question 23

when glucose levels are low

Answer 23

• glucagon and epi released
• GCPR pathway
• cAMP made from ATP
• activate PKA
• activate phosphorylase kinase
• inactivates glycogen synthase
• phosphorylation of glycogen phosphorylase (a form) initiates glycogen degradation

Question 24

step 1 of glycogen synthesis

Answer 24

• glucose-6-phosphate -> glucose-1-phosphate

- via phosphoglucomutase

Question 25

step 2 of glycogen synthesis

Answer 25

- glucose-1-phosphate -> UDP-glucose | - via UDP-glucose pyrophosphorylase

Question 26

step 3 of glycogen synthesis

Answer 26

- glycogenin primes the initial synthesis of a short glucose chain using UDP-glucose as a substrate

Question 27

step 4 of glycogen synthesis

Answer 27

- glycogen chain extended with more glucose | - via glycogen synthase and UDP-glucose

Question 28

step 5 of glycogen synthesis

Answer 28

- glycogen branches creating by transferase (branching enzyme) - breaks 1,4 links and forms 1,6 links - occurs about every 12 residues

Question 29

important hormone in glycogen synthesis

Answer 29

- glycogen synthase

Question 30

insulin signaling and glycogen storage

Answer 30

- insulin released from pancreas - activates glycogen synthase kinase (a form) - activates phosphatase 1 - removes phosphate from glycogen synthase, which activates it

Question 31

Type I glycogen storage disease

Answer 31

- Von Gierke

Question 32

Von Gierke cause

Answer 32

- defect in glucose-6-phosphatase - glucose can't be transported from liver - glycogen accumulates in liver - excess glucose-6-phosphate results in high rates of glycolysis with high levels of lactate and pyruvate in the blood

Question 33

Von Gierke symptoms

Answer 33

- massive liver enlargement - hypoglycemia - weakness

Question 34

Type II

Answer 34

Pompe Disease

Question 35

Pompe disease cause

Answer 35

- defect in lysosomal alpha glucosidase that breaks down glycogen in lysosomes - leads to increased membrane bound glycogen

Question 36

Pompe disease symptoms

Answer 36

- muscle and nerve damage

Question 37

Type III

Answer 37

- Cori disease

Question 38

Cori disease cause

Answer 38

- defect in debranching enzyme - increase of glycogen with short outer branches - can't break down well - only a limited amount of glucose can be released

Question 39

Cori disease symptoms

Answer 39

- like Von Gerke but milder

Question 40

Type IV

Answer 40

- Andersen disease

Question 41

Andersen disease cause

Answer 41

- defect in branching enzyme | - keep making longer branches

Question 42

Andersen disease symptoms

Answer 42

- usually fatal | - liver can't handle longer branches of glycogen

Question 43

Type V

Answer 43

- McArdle disease

Question 44

McArdle disease cause

Answer 44

- defect in muscle glycogen phosphorylase | - no glycogen metabolized

Question 45

McArdle disease symptoms

Answer 45

- exercise induced muscle pain - cramps - weakness

Question 46

type VI

Answer 46

- Hers disease

Question 47

Hers disease cause

Answer 47

- defect in liver glycogen phosphorylase

Question 48

Hers disease symptoms

Answer 48

- mild hypoglycemia | - hepatomegaly

Question 49

two pathways of alcohol metabolism

Answer 49

- alcohol dehydrogenase - modest levels of ethanol | - MEOS - high levels of ethanol

Question 50

alcohol dehydrogenase system

Answer 50

- alcohol dehydrogenase in liver oxidizes ethanol to acetaldehyde and generates NADH - acetaldehyde is converted to acetate by acetaldehyde dehydrogenase and generates NADH - acetate released into bloodstream for use by tissues

Question 51

acetaldehyde and drinking

Answer 51

- acetaldehyde is the negative effects of drinking | - nausea, etc

Question 52

alcohol dehydrogenase

Answer 52

- low Km for ethanol | - active at low ethanol concentrations

Question 53

ALDH2 human variants

Answer 53

- have acetaldehyde dehydrogenase with low Km and low activity (Vmax) - low levels of ethanol result in nausea

Question 54

disulfiram

Answer 54

- inhibits acetaldehyde dehydrogenase | - used to treat alcoholism

Question 55

MEOS system

Answer 55

- metabolizes alcohol to acetaldehyde requiring NADPH | - highest activity is CYP2E1

Question 56

CYP2E1

Answer 56

- high affinity - functions at high levels of alcohol consumption - results in increased production of free radicals and tissue damage

Question 57

result of NADH buildup in liver

Answer 57

- fatty acid oxidation is inhibited - fat accumulation in liver - acetyl CoA shifted away from TCA cycle toward ketone body production - lactate dehydrogenase reaction shifted toward lactate production

Question 58

lactate dehydrogenase reaction shifted toward lactate production

Answer 58

- lactic acidosis | - lactic acid competes with uric acid in kidney for excretion

Question 59

lactic acid competes with uric acid in kidney for excretion

Answer 59

- decrease in uric acid excretion - uric acid crystals - gout!