ATP-ADP Translocase

ATP-ADP Translocase

• While ATP is produced in the mitochondrial matrix, it is needed elsewhere

• The backbone for ATP and ADP is not made in mitochondria

• Thus, ATP and ADP are shuttled in and out of the mitochondrial matrix

• ANTIPORT

How ATP leave mitochondria & ADP and Pi enter?

• Adenine nucleotide translocase (antiporter) (ADP + ATP)

• ATP synthase (H+)

• Phosphate translocase (symporter) (H2PO4- + H+)

Uncoupling

refers to the disruption or collapse of the mitochondrial proton gradient (disrupting ATP synthesis to generate heat)

• can occur physiologically or chemically

Physiological Uncoupling

Can occur in hibernating animals and in humans within brown adipose tissue (BAT)

BAT (Brown Adipose Tissue)

It is full of mitochondria for the purpose of generating heat

Uncoupling Protein-1 (Thermogenin)

Disrupts the proton gradient in BAT

• uncoupling of phosphorylation from electron transfer

• forms proton-conducting pores in the inner mitochondrial membrane

2,4-Dinitrophenol (DNP) and Chemical Uncoupling

• was tested & used in the early 1900s as a weight loss drug

• was quite successful, but it could not be controlled

• many people taking it or working with it (during the wars) lost significant weight and complained of feeling extreme heat

• it ‘punched holes’ in the inner mitochondrial membrane, disrupting the proton gradient

• uncoupling of phosphorylation from electron transfer

• hydrophobic proton carriers

Glycolysis

• 4 ATP made in the payoff phase but 2 are used

• NET amount made = 2 ATP

• 2 NADH + 2 H + formed in the
  cytosol

• ATP yield depends

• 5 ATP (from malate-aspartate shuttle), OR 3 ATP (from glycerol-3-phosphate shuttle)

• 32 ATP total (or 30 ATP total)

Krebs Cycle

• 2 GTP made

• Phosphate from GTP to ADP = 2 ATP

• 6 NADH + 6 H + , and 2 FADH2

• (6 x 2.5 ATP) + (2 x 1.5 ATP) = 18 ATP

PDH Complex

2 NADH + 2 H + (per 2 pyruvate via one glucose)

• 2 x 2.5 ATP = 5 ATP

ATP via one glucose:

• Glycolysis: 2 ATP + “depends”

• PDH complex: 5 ATP

• Krebs Cycle: 2 ATP + 18 ATP = 20 ATP

The two (NADH + H +) from glycolysis:

Need to get to the mitochondrial matrix, but this occurs via two routes:

1. Malate-aspartate shuttle

2. Glycerol-3-phosphate shuttle

Malate-Aspartate Shuttle

2 NADH are indirectly transferred into the mitochondrial matrix = 5 ATP from 2 NADH

• Malate-α-ketoglutarate transporter

• Glutamate-aspartate transporter

Glycerol-3-phosphate Shuttle

Electrons from 2 NADH are transferred to 2
FAD = 3 ATP from 2 FADH2

• Glycerol-3-phosphate

• Dihydroxyacetone phosphate

NADH + H+ (intermembrane space (P side)) → Glycerol-3-phosphate → FADH2 (mitochondrial glycerol 3-phosphate dehydrogenase) → QH2 (mitochondrial matrix)  → Complex III 

What affects ATP yield from glucose?

• exercise

• loss of Krebs Cycle intermediates

• loss of electrons in the electron transport chain

• uncoupling

Cyanide and Carbon Monoxide

• inhibition of electron transfer

• inhibit cytochrome oxidase

A “fresh, out of the box ‘Electron Transport Chain’”

• Is always fully-oxidized

• Inhibition of any portion of the chain will result in reduction in all steps prior to the inhibition site, and oxidation in all steps including and after the inhibition site

• Inhibition of Complex I will not stop the transport of electrons from Complex II