PHSC 208, L30

Non-shivering Thermogenesis

uncoupling electron transport systems in brown fat mitochondria to create heat, activated by binding free fatty acids from triglyceride lipolysis

• important in infants and hibernating mammals

How does non-shivering thermogenesis work?

1. triglycerides get broken down into their independent fatty acids

2. fatty acids bind to UCP-1 in the matrix

3. UCP-1 translocate into internal membrane

What is the major weakness of aerobic metabolism?

Oxygen is dangerous around other electrons because its standard reduction potential is high

Electrons can leak from ETS and react with the O2 to form ROS (reactive oxygen species)— damage any molecules they encounter

O2 + e^- → O2^-

= superoxide

damaging to cells/life

ROS

O2^- + e → O_2² + 2H+ → H2O2

superoxide + electron= peroxide

peroxide + hydrogen= hydrogen peroxide

• free radical, damage macromolecules

  ROS

SOD (superoxide dismutase)

• turns superoxides into hydrogen peroxides

  2O2 + 2H+ → H2O2, reducing damage by converting them into less harmful molecules

• SOD1 mutations induce motor neuron degeneration= ALS

Catalase

enzyme that converts hydrogen peroxide into water and oxygen, protecting cells from oxidative damage

2H2O2 → 2 H2O + O2

• found in peroxisomes, erythrocytes, phagocytic white blood cells

Glutathione Peroxidase

reduction of peroxides of fatty acids prevents secondary chain reactions

Peroxiredoxins (PRX)

• reducing hydrogen peroxide to water

• Cysteine thiol-disulfide, protein gets oxidized and forms disulfide bond (bond called cysteine)

Vitamin E (alpha-Tocopherol)

• has phenolic structure

• absorbs free radicals

• hydrophobic bc of their structure, helps protect the membrane

Vitamin C (Ascorbate)

• water soluble- aqueous compartments and extracellular environment

  • protects membranes by reducing Vitamin E

• humans, guinea pigs, bats, dry-nosed primates cant make

Beta-Carotene

• protect plant cells from ROS generate in photosynthesis

iClicker: Reduced glutathione can be used to protect against damage by reactive oxygen species in a cell by

a. reducing disulfides in proteins

b. detoxifying superoxide

c. detoxifying hydrogen peroxide

d. creating an oxidizing environment

e. reducing lipid peroxides

e. reducing lipid peroxides

How do cells maintain a “redox state”

• ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)

  • this ratio determined by ration of NADPH/NADP+

  • NADH is primary driver of maintaining redox state of cells

Oxidative stress

When ROS generated faster than they can be dealt with by cellular coping mechanisms

• major cause of aging and infertility

• damage to DNA/RNA, lipids, etc

• oxidative stress occur during inflammation and infection

Lipid functions

• components of lipid bilayer

• hydrocarbons are an energy source

• intra+inter- cellular signaling

What is an ampitpathic molecule?

monocarboxylic acid and hydrocarbon chain

• hydrophobic and polar zone

Natural fatty acid qualities

• unbranched

• even # of carbons

What is a saturated fatty acid?

no C=C double bond

What is an unsaturated fatty acid?

contains one or more C=C double bonds

Where is the omega carbon?

always at the end