EXAM3_WS5_Metabolism_Cases Flashcards

1
Q

What is Glutathione ?

Glutathione is derived from what 3 AA’s?

A

Antioxidant
Glutamate
Cysteine
Glycine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does G6PDH deficiency affect glutathione?

A

amount of glutathione stays the same but they can’t be reduced and cannot function

(decreases how many glutathiones are reduced)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pyruvate kinase deficiency affects glutathione how?

A

Decreases synthesis of glutathione so there is less available to detoxify ROS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

G6PDH deficiency is the most common defect worldwide. 10% of population but they don’t know it. Why?

A

Pathology only expressed under oxidative stress to erythrocytes (thought to be defense against malaria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Typical G6PDH deficient patient expresses less than 60% of G6PDH activity and only manifests symptoms when subjected to oxidative stress. Why?

A

These conditions cause rise in H202 due to decreased levels of NADPH able to reduce glutathione

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Heinz Bodies are expressed in what disorder?

A

G6PDH deficiency- oxidized and precipitated Hb bound to the plasma membrane lipids

Causes Hemolytic anemia/ jaundice b/c removed by spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What increases oxidative stress?

A

Infections (macrophages use H202)
Antibiotic Bactrim (drugs)
Fava Beans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Pyruvate Kinase (PK) deficiency in RBC’s

A

Decreases ATP (RBC’s only have glycolysis)

  • Decrease NaK-ATPase
  • Decreased Glutathione

PREMATURE RBC DESTRUCTION= ANEMIA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is worse PK or G6PDH deficiency? Why

A

PK b/c its chronic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

G6PDH deficiency is in all cells (PK is only in RBCs) why then does it only affect RBC’s?

A

RBC’s don’t have mitochondria and rely on HMP shunt oxidative branch for NADPH (reduced by G6PDH deficiency)

Other cells have mitochondria and can use MALIC enzyme to make NADPH and can continue to reduce glutathione

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PK impairs ATP while G6PDH impairs NADPH what impact does each have on glutathione levels and oxidized:reduced ratio of glutathione?

A

G6PDH increases oxidized:reduced ratio

PK decreases actual glutathione ratio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Ethanol oxidation in the cytosol (2 rxns)

A

Alcohol dehydrogenase
Aldehyde dehydrogenase

both result in increased NADH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Chronic Ethanol oxidation in the SER (microsomes)

A

CYP2E1 and CYTP450

CYP2E1 Oxidizes NADPH in SER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Ethanol metabolism increases cytosolic NADH and two reactions are forced in order to regenerate NAD+. What are the two reactions used to regenerate NAD+?

A
  1. Pyruvate > Lactate
  2. OAA > Malate

the gluconeogenic intermediates are decreased resulting in profound Hypoglycemia

can produce lactic acidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the role of thiamine in glucose oxidation? and what metabolic processes will slow as a result?

A

Thiamine is precursor for TPP
TPP required by PDHC and aKGDH
Slows TCA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why comatose alcoholics may develop lactic acidosis after infusion with dextrose without thiamine?

A

Alcohol inhibits thiamine absorption (alcoholics may be thiamine deficient)

PDHC inhibited results in pyruvate accumulation in cytosol.
NADH from alcohol metabolism accumulates in cytosol

This forces LDH to make LACTATE to regenerate NAD+

17
Q

Fructose metabolism causes hypoglycemia due to what factors?

A

Decreased Pi:

  1. decreases hepatic glycogenolysis
  2. decreases gluconeogenesis

Leads to hypoglycemia