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Review - II Flashcards

1
Q

Where does glycogenolysis occur?

A

Liver and skeletal muscle

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2
Q

What is beta oxidation?

A

Conversion of FAs to AcCoA

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3
Q

Why is lypolysis?

A

Hydrolyzing triglycerides into FAs and glycerol

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4
Q

Can AAs become AcCoA?

A
  • Yes

- Can be deaminated and oxidized to acetyl CoA

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5
Q

What can happen to AcCoA?

A

Enter TCA cycle
Produce ketone bodies
Produce fatty acids and sterols

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6
Q

What can cause chronic lactic acidosis?

A

PDH deficiency

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7
Q

Genetics of PDH deficiency?

A
  • Predominantly an X-linked dominant

- Caused by mutation in E1 alpha gene

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8
Q

How to treat PDH deficiency?

A
  • Dietary supplementation with thiamine, carnitine, and lipoic acids
  • Dichloroacetate – inhibitor of protein kinase subunit of PDH complex
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9
Q

How much ATP does 1 CAC generate?

A

10

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10
Q

What is generated in CAC and ATP conversion?

A
  • 3 NADH @ 2.5 ATP each = 7.5 ATP
  • 1 FADH2 @ 1.5 ATP each = 1.5 ATP
  • 1 GTP @ 1 ATP each = 1 ATP
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11
Q

2 Key enzymes in CAC?

A
  1. Isocitrate dehydrogenase
  2. Alpha-ketoglutarate dehydrogenase
    - Both can be regulated allosterically and under fine and coarse control
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12
Q

Modulation of Isocitrate dehydrogenase?

A
  • Inhibition - High concentration of ATP

- Activation- High ADP

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13
Q

Modulation of Alpha-ketoglutarate dehydrogenase?

A
  • Activation - High concentration of Ca

- Inhibition - High amount of NADH

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14
Q

How does Succinyl CoA Feedback?

A
  • High concentrations inhibit conversion of Acetyl-CoA to citrate
  • Also inhibits formation of additional succinyl CoA
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15
Q

What usually provides Oxaloacetate in CAC?

A

Fumarate

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16
Q

What can provide OAA in lieu of fumarate?

A

Asparate

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17
Q

What usually provides alphaketoglutarate in CAC?

A

Citrate

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18
Q

What can procide alphaketoglutarate if shortage of citrate?

A

Glutamine

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19
Q

What can provide propinyl coA in CAC?

A

Valine

Isoleucine

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20
Q

What is performed first during starvation?

A

Glycogenolysis

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21
Q

Sources for gluconeogenesis?

A

Pyruvate
Lactate
Glycerol
Glucogenic amino acids

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22
Q

Where does gluconeogenesis occur?

A

Liver

Kidney

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23
Q

What does muscle release from stored glycogen?

A

Lactate

Alanine

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24
Q

Does gluconeogenesis require ATP?

A

Yes

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25
Where does ATP for gluconeogenesis come from?
- Overnight metabolism of fatty acids
26
What is PEP?
- Activated form of pyruvate
27
What is intermediate between PEP and pyruvate?
OAA
28
What else is required for pyruvate to PEP conversion?
- Bicarb - Biotin - Expenditure of ATP
29
Gluconeogenic precursors?
- Fructose - Galactose - Glycerol - Propionate - Aspartate - Alanine - Lactate
30
What is Cori Cycle?
- Generation of glucose from lactate - Lactate gets into the liver and generates a glucose molecule - Utilizes 6 ATP in the process
31
Where does cori cycle happen?
Lactate comes from RBCs & skeletal muscle | Then moves to liver
32
What is alanine cycle?
Gluce from alalanine
33
Where does alanine come from?
Skeletal muscle in exercise
34
Byproduct of alanine cycle?
Ammonia which is turned into urea
35
4 key enzymes in glycogenolysis?
1. Pyruvate carboxylase - mitochondrial 2. PEP carboxykinase 3. Fructose 1,6 biphosphatase 4. Glucose 6 phosphatase
36
What happens in Pyruvate carboxylase deficiency?
- Cannot convert pyruvate to oxaloacetate - Increased alanine, lactate, and pyruvate - Lack of enzyme reduces gluconeogenesis process and reduces the urea cycle - Recurrent seizures - Developmental Delay - Metabolic acidosis
37
What happens in Glucose 6 phosphatase deficiency?
- Blocks gluconeogenesis and glycogenolysis - Cannot generate glucose from glucose-6-phosphate - Glycogen storage disease type I (von Gierke disease) - Increased liver size and elevated serum uric acid and lactate levels - Poor tolerance of fasting - Growth retardation - Hepatomegaly
38
What does ethanol ingestion cause?
- Hypoglycemia because the high amount of NADH opposes gluconeogenesis - Ethanol metabolism raises NADH/NAD ratio - Removes pyruvate and OAA from pool of glucogenic precursors
39
What does high NADH cause?
- Conversion of pyruvate and OAA to lactate and malate
40
How does glucose enter hepatocyte?
Glut2
41
What does G6P do?
Convert G6P to Glucose
42
Transporter on skeletal muscle?
GLUT4
43
Muscle or liver store more glycogen?
Muscle
44
What stimulates glycogen break down in muscle?
Epinephrine or muscle contraction
45
Why cant skeletal muscle synthesize glucose?
- There is no G6Pase in skeletal muscle
46
Summary of steps of glucose storage?
- Glucose can be converted to G6P - G6P is converted to G1P - From there G1P is converted to UDP glucose - Glycogen synthase and branching enzyme converts UDP glucose to glycogen
47
What converts glycogen to G1P?
Debranching enzyme and glycogen phosphorylase
48
Which form of glycogen phosphorylase is phosphorylated?
- B is dephosphorylated - A is phosphorylated - A is Active
49
What leads to conversion of phosphorylase A to B?
- Increased levels of glucose and insulin favor glycogen storage - Activates phosphoprotein phosphatase - Dephosphorylates active form of phosphorylase a - At the same time, glycogen synthase is activated
50
Allosteric regulation of glycogen phosphorylase?
- AMP converts B to A - ATP converts A to B - High glucose inactivates A
51
Active and inactive forms of glycogen synthase?
- A is dephosphorylated - B is phosphorylated - A is active
52
Regulation of glycogen synthase?
- Insulin leads to activation - Glucagon leads to inhibition - G6P binds to B activating it
53
What does G6P dehydrogenase do?
- Catalyzes first step in pentose phosphate pathway | - Converts G6P to 6-phosphogluconate
54
What does pentose phosphate pathway create?
- Penthose phosphate pathway generates lots of NADPH
55
How is o G6P dehydrogenase deficiency inherited?
X linked
56
What does G6P dehydrogenase deficiency cause?
- Hemolytic anemia - RBCs cannot handle oxidative stress in absence of G6P dehydrogenase - Increased bilirubin - Decreased hemoglobin
57
What does NADPH doe in RBC?
- Maintains glutathione in reduced state - Protect RBCs against oxidative stress - If NADPH levels reduced, glutathione can be oxidized - Oxidation produces hydrogen peroxide as a byproduct - Toxic to RBCs
58
What does glutathione do?
Protects RBC from oxidative stress
59
What is drug than can generate oxidative stress?
Dapsone, used for malaria
60
What can increase oxidative stress?
- Oxidative drugs (anti-malaria drugs like dapsone) - Infection (produces free radicals) - Favism
61
Symptoms of PDH deficiency?
- Elevated Serum lacate, pyruvate - Microcephally - Poor muscle coordination - Mental retardation
62
What can succily coA come from?
Propionyl coA or alphe ketoglutarate
63
Where does fumarate usually come from?
Siccinyl CoA
64
What can also create fumarate?
Phenylalanine Aspartate Tyrosine
65
How much ATP does alanine cylcle use?
10
66
What does cAMP do do glycogen phosphorylase?
Increases its activity

Metabolism (17 decks)

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