Metabolic Integration

Question 1

What are the 3 substrates required for Gluconeogensis? Where do they enter the cycle?

Answer 1

1. Amino Acids - enter TCA cycle to form oxaloacetate
2. Glycerol - eventually gets converted to Glyceraldehyde 3-phosphate
3. Lactate/Alanine - enter as pyruvate from CORI cycle which gets converted to oxaloacetate

Question 2

Where is the energy created to conduct gluconeogenesis?

Answer 2

Fatty Acid Oxidation

Beta Oxidatin of Fatty acids leads to aceytl CoA production which can enter the TCA cycle and produce ATP.

However, since oxaloacetate is being consumed in gluconeogenesis, many acetyl CoA are converted to ketone bodies.

Question 3

What are the 4 central themes of metabolism?

Answer 3

1. ATP is the universal energy currency
2. NADPH is the major electron donor in reductive biosynthesis
3. There are a few building blocks that many cells use (ie - actyl CoA)
4. Biosynthetic and Degredative pathways are almost always distinct from each other.

Question 4

Name 3 molecules that are key junctions or connections between metabolic pathways?

Answer 4

1. Glucose 6-phosphate
   
   1. Glycolysis, Gluconeogenesis
   2. Pentose phosphate pathway
   3. Glycogen
2. Pyruvate
   
   1. Glycolysis, Gluconeogenesis
   2. TCA
   3. Cori Cycle
3. Acetyl CoA
   
   1. Cholesterol, Ketones
   2. TCA
   3. Fatty Acids

Question 5

What are teh 5 common characteristics of metabolic regulation?

Answer 5

1. Allosteric Interactions
   
   1. downstream products inhibit upstream
2. Convalent modifactions
   
   1. inactive–>active enzyme
3. Adjustment of enzyme levels
   
   1. Gene regulation increases enzyme levels
4. Compartmentation
   
   1. fatty acids are degraded in mitochondria, but synthesis occurs in cytosol
5. Metabolic Specialization of organs
   
   1. Tissues have same pathways, but are regulated differently

Question 6

What are the 2 pathways ethanol (alcohol) is metabolized?

Answer 6

1. Alchohol Dehydrogenase
2. MEOS (Microsomal Ethanol Oxidizing system) - P450 enzymes

Question 7

Describe the MEOS mechanisms for alcohol degradation?

Answer 7

The MEOS uses oxidation of NADPH to NADP+ to degrade alcohol into acetaldehyde.

Question 8

What is one potential downside of using the MEOS to degrade alcohol?

Answer 8

When the MEOS is system is turned on it provides drugs and toxins an alternate to detoxification. However, MEOS does not detoxify certain substances similarily. For example tylenol is turned into a poison when broken down by the MEOS.

Question 9

Describe the mechanism for alcohol detoxification by Alcohol dehydrogenase?

Answer 9

Alcohol–>Acetaldehyde–>Acetic Acid–>Acetyl-CoA–>TCA

Question 10

What biochemical Ratio increases during alcohol consumption?

What effect does this have on the body.

Answer 10

NADH/NAD+ increases.

An increase in NADH leads to the following:

• Pyruvate is shifted towards lactate
  
  • Shuts down Gluconeogenesis–>hypoglycemia
  • Inhibts excretion of uric acid
• Makes Glycerol 3-phosphate which leads to triglyceride synthesis
  
  • hyperlipidemia
• Oxaloacetate is converted to malate (reverses TCA cycle)
  
  • Acetyle CoA is converted into ketones–>ketosis