Energy And Heat Production

Front 1

How do we obtain energy from nutrients?

Back 1

- remove the e- essentially to make ATP

Front 2

How do we make ATP?

Back 2

in the mitochondria using the electron chain
- also via direct breakdown of nutrients (Anerobic)

Front 3

How is heat generated?

Back 3

- result of biochemical activity

Front 4

What controls heat generation?

Back 4

Hormones; such as thyroid, adrenalin... under Hypothalamic control

- skeletal muscle
- brown adipose tissue
- futile cycling

Front 5

How can heat generation be increased?

Back 5

•increased ATP utilization
•reduced efficiency of ATP synthesis

Front 6

Thermogenesis (Heat Production)
2 forms

Back 6

Obligatory: associated with the resting metabolic rate (relaxed subject @ standard temperature: 23 ˚C)

Adaptive (facultative): increased metabolic rate (e.g., due to decreased temperature, increased food intake)

Front 7

Regulation of adaptive thermogenesis

Back 7

Sensing arm: Hypothalamus (temperature and nutrient sensors)

Effector arms: Thyroid hormone Sympathetic Nervous System

Front 8

Control of thyroid hormone release

Back 8

Front 9

Thyroid hormones Chemical Structure

Back 9

amines
- modified from tyrosine

Front 10

Sites of Adaptive Thermogenesis

Back 10

1. Brown Adipose Tissue
- Large numbers of mitochondria (cytochromes are brown)
- Mitochondria a key site of heat generation
2. Skeletal Muscle
- Acute (Shivering): ATP breakdown via “futile” contractions
- Prolonged: Changes in muscle fibre phenotype; enhanced mitochondrial biogenesis & SERCA (smooth ER Ca ATPas) expression
3. Futile metabolic cycles

Front 11

Location of brown adipose tissue in Adults

Back 11

- there isnt much brown adipose tissue in adults
- MOST particularly around the heart in the mediastinum

Front 12

How is heat produced from metabolism?

Back 12

1. ATP breakdown without work
2. Coupling opposed pathways to one another (futile cycles)
3. Impaired efficiency of ATP-dependent ion transport (e.g. Ca2+ transport from Cytoplasm to SER store via SERCA)
4. Uncoupling nutrient metabolism from ATP synthesis (i.e., metabolism without energy storage)

Front 13

Futile Cycle of Glycolysis

Back 13

Front 14

Heat Production from skeletal muscle cells

Back 14

1. futile cycling of Ca2+
2. Shivering

Front 15

Another example of heat generation from ion transport
Na

Back 15

•
Na+ leak across plasma membrane activates Na+/K+-ATPase to pump them out again
•
Net effect is ATP break down and heat generation
•
Thyroid hormone may increase membrane Na+ permeability

Front 16

How is ATP synthesized in mitochondria?

Back 16

- electron transport chain then driving complex V via a proton pump to make ATP

Front 17

How can mitochondria act as sites of heat production?

Back 17

- UCP
- reduced efficacy
- Complex II rather than I shunting

Front 18

What is the origin of the energy value of food?

Back 18

A. Its electrons.

Glycolysis, Fatty Acid Oxidation, Citric Acid Cycle:
Electrons stripped from major nutrients (carbohydrate, fat, protein)
Mitochondrial electron carriers loaded up: NADH and FADH2

Front 19

How do NADH and FADH2 promote:
ATP synthesis?
OR
HEAT?

Back 19

Electrons are transferred between complexes Complex V is an ATP synthase when electrons flow Electron flow is coupled to ATP synthesis

Front 20

How is electron flow coupled to ATP synthesis?

Back 20

1. Electron flow is coupled to proton pumping
2. Complexes I, III and IV are electron-driven proton pumps
3. Protons accumulate in intermembrane space (IMS); pH drops to 3
4. H+ flux back through complex V drives ATP synthesis

Front 21

How is heat generated from mitochondria?

Back 21

Oxidative phosphorylation is uncoupled
UNCOUPLING PROTEIN (UCP) provides alternative route for H+ re-entry
Heat arises from futile recycling of protons

Front 22

UCP

Back 22

UCP-1 in brown adipose tissue
UCP-2 is widely expressed and under thyroid control
UCP-3 expressed in skeletal muscle and under thyroid control

Front 23

How is heat production regulated by thyroid hormone?

Back 23

1. Increased expression of uncoupling proteins (e.g., UCP-2; UCP-3*)
2. Reduced efficiency of mitochondrial proton pumping
3. Feeding electrons via complex II rather than complex I (less proton pumping)** (Glycerol 3-phosphate shuttle)
4. Thyroid hormone promotes SERCA expression and impairs its efficiency
5. Sympathetic nervous system effects: Enhanced β2-adrenergic receptor expression in muscle

Front 24

Roles of other hormones in control of heat production

Back 24

1. Adrenalin: stimulates hepatic gluconeogenesis; induces vasodilatation in skeletal muscle; promotes conversion of T4 to T3 (deiodinase-2 expression)
2. Leptin: promotes activation of the sympathetic nervous system
3. Insulin: Cold exposure increases glucose uptake and metabolism (especially in fat cells)
4. Glucagon: Stimulates gluconeogenesis

Front 25

Measurement of Heat Production

Back 25

Direct calorimetry: expensive and time consuming (heat porduction is slow)

1. Indirect Calorimery: measure O2 cunsumption (depletion of O2 in expired air)
2. Doubly-labelled Water*: compare water and CO2 excretion