Integrated metabolism: Mitochonrdion

ATP as an allosteric inhibitor

Inhibits PFK which pauses glycolysis

AMP

• Large concentration means low amount of ATP

• Stimulator of PFK

Citrate

• An allosteric inhibitor of PFK

• Lots of citrate means krebs cycle is saturates

UCP-1

• Aka thermogenin

• Provides a different path of H+ to enter mitochondrial matrix

• Uncouples the ETC & ATP synthase

How UCP-1 releases heat

• Only in warm blooded mammals & some plants

• Use H+ to release heat

• This maintains body temperature

Glycolysis → krebs cycle

Central metabolic pathway

NH3

• A toxic inhibitor of krebs cycle

• Discarded in urine

• Waste from amino acids

Glucose when PFK is inhibited

• Can still become G6P and F6P

• Gets put into storage as glycogen

Insulin

• Hormone made by α cells in pancreas

• Promotes anabolic pathway

Anabolic pathway

Synthesis of glycogen

Glucagon

• Hormone made by β cells in pancreas

• Promotes catabolic pathway

Catabolic pathway

Breaking down glucagon into glucose

Skunk cabbage

Generates heat using AOX & thermogenin to melt snow in the spring

Hibernating animals

Use UCP-1 to maintain a safe body temp & sustain a basal level of metabolisn

Cold blooded animals

• Don’t have thermogenin

• Require 1/10th of the energy used by warm blooded species

UCP-1 is is exclusive to _

Placental mammals

Metabolism of carbohydrates

Converted to glucose or to glycolysis intermediates & enter the glycolytic pathway

Metabolism of proteins

• Proteins are broken down into amino acids

• Amino acids have their α group removed & discarded through urine

• Remnants enter respiration as CMP intermediates

Metabolism of fats

• Split into glycerol & fatty acids

• Glycerol enters glycolysis as DHAP

• Fatty acids are cleaved through β-oxidation in mitochondria

β-oxidation of fatty acids

1. CoA is added to the fatty acid

2. Fatty acid + Acetyl-S-CoA are cleaved & hydrated

3. Acetyl-CoA is created

β-oxidation outputs

1 FADH2, 1 NADH, 1 acetyl-coA

Acetyl yield in β-oxidation of fatty acids

n/2, where n is the number of carbons the fatty acid has

Number of rounds in β-oxidation of fatty acids

n/2 - 1, where n is the number of carbons the fatty acid has

Brown fat

• Produce heat

• Babies have a lot of it

Mitochondria in RBC

They don’t have it, so they have to ferment. Lactate waste is dumped into the blood

Glucose uptake

• Insulin binds to a receptor

• Receptor signals vesicles to move GLUT4 to the membrane

• Glucose enters the cell through GLUT4

Tissues that are not dependent on insulin for glucose uptake

• The brain, liver, and heart

• Contain high amounts of GLUT1 & GLUT3 in their membranes

Tissues that require insulin for glucose uptake

• Skeletal muscles

• Adipose tissue

• Contain low amounts of GLUT1 in their membranes

GLUT 1 & GLUT3

Glucose transporters not dependent on insulin

Mobile sugar in plants

Sucrose

Too low glucose (hyperglycamia)

Causes fainting, < 3 mmol /L glucose

Normal level of glucose

4-5 mmol/ L glucose

Prediabetes level of glucose

5-6 mmol / L glucose

Diabetes level of glucose

> 7 mmol / L glucose

Type 1 diabetes

• Genetic

• Not enough / no insulin is produced

• GLUT4 cant be brought to the membrane & glucose accumulates in blood

• 10% of diabetes mellitus cases

Type 2 diabetes

• Insulin is produced

• Insulin cells do not respond to insulin (insulin resistance)

• GLUT4 cant be brought to the membrane & glucose accumulates in blood

Diabetes treatment

• Eating healthy

• Exerscise

• Insulin when needed

Exercise-induced glucose uptake

• Muscle cells recruit GLUT4 to the membrane independently of insulin

• Can be done with CaMK or AMPK pathway

• Last hours after exercise

Irisin

• Regulates UCP-1 to lipid clearance in the recovery phase after exercise

• Temporarily turns white adipose tissue into beige adipose tissue to increase the fat-burning capacity

Exposure to cold temperatures

UCP-1 is upregulated

3 ways muscles regenerate ATP

• Respiration (O2)

• Glycolysis followed by fermentation

• Phosphocreatine (independent)

Glycogenesis

• Storing of glucose as glycogen

• Stimulated by insulin

Glycogenolysis

• Breakdown of glycogen into glucose

• Stimulated by glucagon

Gluconeogensis

• Manufacturing of glucose from other molecules

• Krebs cycle → “reversed glycolysis”

Cori cycle

1. RBC or muscle cell uses glucose for lactic acid fermentation

2. It drops the lactate waste into the blood

3. Liver cell receives the lactate

4. “Reverse glycolysis” happens

5. The created glucose is put into the blood

6. Net loss of 4 ATP