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

What is the relationship between an animal’s metabolic rate and temperature?  How does the metabolism contribute to thermoregulation?

Metabolic rate will increase BOTH when the animal passes its lower critical temperature, and its upper critical temperature

What is shivering thermogenesis?

An involuntary motor muscle response

• Muscle contraction of antagonistic muscles

  • Contraction, but little net movement

• Produces heat through hydrolysis of ATP

Is metabolically expensive and relatively inefficient

What is non-shivering thermogenesis?

Brown adipose tissue is metabolically active, has many mitochondria:

• Cold is sensed by the brain, activating the sympathetic nervous system and resulting in the release of noradrenaline 

• This triggers the production of cAMP, which creates Protein Kinase A which will stimulate lipolysis of that brown adipose tissue

  • Acute effects:

    • Stimulation of lipolysis

    • Activation of UCP-1 activity

  • Chronic effects:

    • UCP-1 gene transcription

    • Mitochondrial biogenesis

    • Hyperplasia of brown adipose tissue

    • Recruitment of brown adipocytes in white adipose tissue deposits

What is the uncoupling protein 1 (UCP-1) in non-shivering thermogenesis, and what is its significance?

Is found in the inner mitochondrial membrane

• Protons BYPASS ATP synthase and leak back across the membrane VIA UCP-1

  • Energy is dissipated as heat

This is THE CATALYST for non-shivering thermogenesis

What is non-shivering thermogenesis’ roll in hibernation?

Induces spikes in body temperature in the animal, effectively bringing them out of hibernation 

• Allows them to:

  • Drink / eat

  • Urinate / defecate

  • Cellular repair and proteostasis

  • Activates the previously dormant immune system

  • Counters “sleep debt”

Briefly describe non-shivering thermogenesis in neonates…

The peri/postnatal catecholamine surge (norepinephrine, epinephrine, dopamine) triggers non-shivering thermogenesis in neonates, which is essential for babies to survive going from the mother’s womb to colder temperatures

• Only happens in animals that have been NATURALLY BIRTHED

• In animals that have been birthed via c-section, NST isn’t triggered

  • Leads to metabolic stress 

How does obesity affect an individual’s ability to perform non-shivering thermogenesis?

Overall, obese individuals possess LESS brown adipose tissue than lean individuals

• Also more difficult to trigger NST due to white adipose tissue acting as an insulator

What is one complication of non-shivering thermogenesis in pigs?

Farm pigs lack a functional UCP-1 protein

• Are very cold sensitive

• Neonates subject to hypothermia

What is the sarcoplasmic reticulum Ca2+ ATPase enzyme, and what is its function?

The SERCA pump contributes to non-shivering thermogenesis (NST) by using ATP to pump calcium (𝐶𝑎2+) into the sarcoplasmic reticulum (SR) of the mitochondria for muscle relaxation

• Its activity can be "uncoupled" by proteins like sarcolipin (SLN). This uncoupling causes the pump to hydrolyze ATP and release heat without effectively transporting calcium, creating a futile cycle that generates significant heat, increasing energy demand, and maintaining body temperature without shivering

• VERY energetically expensive

What genetic mutation do pigs have that affects the SERCA enzyme, and what does it cause?

Pigs have an inherited mutation of the ryanodine receptor, making the SERCA enzyme much more permeable to calcium 

• Causes a calcium build up into muscle 

• Result of stress, exercise, and heat 

This causes pigs to be more susceptible to HYPERTHERMIA in general, can die of heat stress very easily

What is the relationship between metabolic function and aging?

Metabolic function rapidly DECLINES as an individual ages, affecting things like body functions, reproductive ability, and disease resistance

How do the aging rates BETWEEN species differ from the aging rates WITHIN species?

BETWEEN species:

• Animals that are larger tend to have longer lifespans

• Ex: Elephant will live much longer than a mouse

WITHIN species:

• Is the opposite

• Dogs that are larger tend to have SHORTER lifespans than smaller dogs

How does mitochondrial aging contribute to increased physical aging?

Mitochondrial aging produces more ROS, which can be damaging as they increase in concentration

• Are the primary drivers in aging in individuals

• Causes oxidative damage to telomeres, lipids, and proteins

• Cause functional decline associated with aging as well

What is Alkaptonuria?

A mutation in homogentisate 1,2 dioxygenase (HMG) gene

• Causes an inability to metabolise tyrosine and phenylalanine

• Results in a build-up of Homogentisic acid- oxidises to pigment (ochre) 

  • AKA: “Black urine disease”

  • Urine turns dark when left standing due to oxidation of homogentisic acid

Symptoms:

• Ochronotic arthritis

• Calcification of invertebral discs

• Kidney stones

• Valve stenosis

What is Fanconi syndrome?

Proximal kidney tubule dysfunction

• Causes urinary loss of ESSENTIAL electrolytes and nutrients

• Inherited form of disease is due to a mutation in the gene that encodes enoyl-CoA

  • Causes impaired fatty acid oxidation, mitochondrial dysfunction, and impaired functionality of the proximal kidney tubule

• Results in:

  • Growth retardation

  • Diarrhoea

  • Hypokalaemia

  • Hyponatraemia

  • Hypochloraemia

Image shows two heifers of the same age… first one has Fanconi syndrome, second one is healthy

What is MELAS disease?

Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes

• Clinical signs in humans usually between 2-15 years 

Caused by a mutation in tRNA gene MT-TL1

• tRNA^Leu involved in assembly of OXPHOS Complex 1

• Results in:

  • Seizures, recurrent headaches, vomiting, hemiparesis, vision and hearing loss, loss of motor skills, cardiomyopathy and intellectual disability

Telltale sign:

• Urine has odor of burnt sugar

What is Maple syrup urine disease?

IS DIFFERENT FROM MELAS

Inherited aminoacidopathy

• Dysfunction in mitochondrial branch-chain keto acid dehydrogenase (BCKDH)

• Build-up of leucine, valine and isoleucine- BCAA

In general, causes damage to mitochondrial DNA, reduced mitochondrial metabolism, apoptosis

• Urine smells of maple syrup (in humans)

• More common in Hereford cattle 

Clinical signs within 2-4 days of age

• Dullness, recumbency and opisthotonos

• CNS dysfunction if not treated.