Aerobic and Anaerobic Resp. Part 1 (Week 2, Mod 9)

Buckle up, cause both these lectures were awful

What are the main differences between nuclear DNA and mitochondrial DNA?

Nuclear DNA

• Double helix structure

• Has THOUSANDS of protein-encoding genes (~2000)

mtDNA

• Circular, double-stranded DNA

• Only 37 protein-encoding genes

Describe the endosymbiosis theory…

mtDNA is much more similar to bacterial DNA than eukaryotic DNA, so the theory is that the mitochondria was once a prokaryote that developed a mutually beneficial symbiotic relationship with a eukaryotic cell

Is mtDNA inherited?

Yes, but ONLY maternally

• Paternal mtDNA is eliminated during spermatogenesis

If the mitochondria has its own DNA, does this mean that it can regenerate itself?

No

• mtDNA encodes very few of its own proteins; its other proteins are encoded by nuclear DNA and need to be transported across the mitochondrial membrane 

• Also needs nutrients and oxygen to pass through the mitochondrial membrane as well

What are the 2 different transporters that can get proteins and nutrients across the mitochondrial membrane?

• Porins - found on the outer mitochondrial membrane, are small channels that allow for passive diffusion 

• Translocases - use active transport to get larger complexes across the membrane 

  • TOM - translocator OUTER membrane

  • TIM - Translocator INNER membrane 

What metabolic process happens at the INNER mitochondrial membrane?

Oxidative phosphorylation

• Via Electron Transport Chain

• Makes ATP

Describe the relationship between different kinds of tissues and their energetic needs…

Tissues that are active and expending a lot of energy, then have a higher metabolic rate in turn

• Ex: contracting muscle has a much higher metabolic rate than other tissues, all except for the heart during heavy exercise

• Because of this, contracting muscles will have a higher density of mitochondria

What are the two different ways that mitochondria can interact with each other? What can happen as a result of these?

Mitochondria can either:

• Fuse

  • Increases ATP production

  • Increases mitochondrial mass

  • Increases mtDNA mixing

• Fission

  • Decreases ATP

  • Increases NUMBER of mitochondria

  • Causes mtDNA segregation

Mutations in mtDNA can occur during either of these pathways and affect the individual

What is an example of a neuromuscular disease that is caused by mitochondrial fusion?

MFN2 mutation (Charcot-Marie-Tooth disease)

• is a group of inherited neurological disorders that damage the peripheral nerves, leading to progressive muscle weakness, atrophy, and sensory loss, typically starting in the feet and legs (causing 'foot drop' and high arches/hammertoes) before affecting the hands and arms

Can be seen in canines of some species. Causes:

• MEGAESOPHAGUS - biggest telltale sign

• Laryngeal paralysis

• Regurgitation

• Quiet barking

• Loud breathing

What is the relationship between how many mitochondria an individual has and their overall metabolic needs?

Essentially, more active = more mitochondria

What are the 4 main functions of the mitochondria?

1) ATP synthesis - 38 ATP per glucose molecule

2) Production of metabolites (Krebs cycle)

3) Heme, testosterone, and estrogen production

4) Calcium homeostasis

Where does Glycolysis take place in the cell?

In the cytoplasm

• Considered substrate-level phosphorylation; does NOT require oxygen (anaerobic)

What does leftover pyruvate from glycolysis convert into?

LACTATE

What is Type A Lactic Acidosis?

Build-up of (typically) L-lactate in blood leading to excessively low pH

• Leads to tissue hypoperfusion and hypoxia 

• Oxygen consumption/delivery mismatch leading to anaerobic metabolism

Causes:

Hypovolemia

Cardiac failure

Sepsis

Cardiac arrest

What is Type B Lactic Acidosis?

Occurs under normoxia, with no evidence of organ hypoperfusion

• Usually caused by drug or toxin interference of cellular metabolism

• Ex:

  • Cyanide poisoning/alcoholism

  • Metformin

  • Mitochondrial disease

  • Excessive exercise

  • SPECIFICALLY RUMINANTS: Sudden, unaccustomed ingestion of CH-rich feeds in ruminants

    • Grains or concentrates

What is the importance of dietary thiamine (Vit. B1)?

Thiamine pyrophosphate (TPP) is an ESSENTIAL co-factor in the transport of pyruvate from the cytosol of the cell to the mitochondria for the pyruvate dehydrogenase complex (converts pyruvate into acetyl-CoA for further metabolic needs 

• NO aerobic metabolism without it 

What would happen if an animal had a thiamine deficiency?

Would result in:

• Lactic acidosis

• anorexia

• cardiac hypertrophy

• muscle weakness

• convulsions

• TELLTALE SIGN: Opithotonos (star gazing)

What is cf Metabolic Acidosis?

Metabolic processes that produce/manage acids break down

CAUSED BY:

• Antifreeze (Ethylene glycol)

  • Competitive inhibitor of Alcohol dehydrogenase

  • Sweet tasting, toxic even if feet/coat contaminated

  • Breakdown metabolites highly toxic

    • Glycolic  and oxalic acid

    • Calcium oxalate crystals- renal failure

Treatment-  ethanol or 4-MP (Fomepizole)

< 3hrs for cats 

< 8-12 hrs for dogs

What does the Krebs cycle produce?

Takes acetyl CoA and oxidizes it, producing high energy electron donors → 3 NADH and 1 FADH2