Membrane Transport

Which molecules have high membrane permeability?

Small, lipid soluble substances

What are the properties of simple diffusion?

1. For small, nonpolar molecules

2. Moves down a concentration gradient

3. No energy is required

4. No transporter is required

5. Cannot be saturated

6. Nonspecific

What are the properties of facilitated diffusion?

1. For larger, charged compounds

2. Moves down a concentration gradient

3. No energy is required

4. Transport proteins required

5. Can be saturated

6. Specific

What are the properties of primary active transport?

1. Requires energy

2. Establishes a concentration gradient

3. Requires membrane proteins

4. Energy comes from hydrolysis of ATP

What are the properties of secondary active transport?

1. Requires energy

2. Requires membrane proteins

3. Energy comes from coupling unfavorable movement with favorable one

4. Symport if two molecules move in same direction

5. Antiport if two molecules move in opposite directions

Vmax

The maximum rate at which a transporter can work

Km

The substrate concentration at ½ Vmax

How is Km related to affinity?

Inversely proportional

Where is the GLUT1 transporter expressed?

GLUT1 is expressed in all somatic cells, but it is the only glucose transporter in both red blood cells and the blood brain barrier

At normal blood glucose levels, what is the activity of GLUT1?

GLUT1 is functioning at full capacity at normal glucose levels.

What are the effects of a homozygous mutation in GLUT1?

Death

What are the effects of a heterozygous mutation of GLUT1?

Mental handicap and epilepsy are common

How are mutations of GLUT1 treated?

Keto diet

Where is the GLUT2 transporter expressed?

Liver and pancreatic beta cells

What triggers the expression of GLUT2?

GLUT2 expression increases as a response to insulin

Why is GLUT2 important if GLUT1 exists in the liver and pancreas?

GLUT2 helps protect against blood sugar spikes. GLUT1 is always functioning at full capacity, so it cannot take in any more glucose after a meal. To keep the blood glucose level from becoming too high, the pancreas releases insulin to trigger the expression of GLUT2 in the liver. The liver absorbs the extra glucoses and converts it into fat.

What is GLUT2’s affinity for glucose in relation to GLUT1?

Lower

What are the effects of a GLUT2 mutation?

Diabetes

Where is GLUT4 primarily expressed?

GLUT4 is only expressed in insulin sensitive tissues

What are the effects of GLUT4?

GLUT4 triggers rapid uptake of glucose in muscle in response to insulin

How does the sodium/potassium pump work?

The sodium gradient is reduced, which opens the voltage sensitive calcium pump. Calcium enters the cell, causing stronger contractions and an increase in heart function

How does the sodium-calcium exchanger work?

ATP is used to establish a sodium gradient, and the energy of sodium entering the cell is used to pump calcium out

What is the role of p-glycoprotein?

Excrete toxins from the cell

Where is p-glycoprotein located?

Liver, kidney, and intestine

Where is SGLT1 located?

Intestine and kidneys

What is the purpose of SGLT1?

SGLT1 pumps both sodium and glucose into the cell to help prevent the waste of glucose during digestion

What are the effects of a mutation in SGLT1?

Severe diarrhea, especially in newborns

How are mutations in SGLT1 treated?

High-fructose diets, since SGLT1 can transport galactose as well as glucose

What causes Hartnup disease?

Malabsorption of neutral amino acids in the nephron

What are the side effects of Hartnup disease?

Dementia, dermatitis, diarrhea

How is Hartnup disease managed in the US?

In the US, the malabsorption of amino acids can be accommodated through the diet and pellegra-like symptoms can be managed with B-complex vitamins

What causes cystinuria?

Malabsorption of cationic amino acids, as well as cystine

What are the symptoms of cystinuria?

Severe kidney stones and kidney damage

How is cystinuria treated?

1. Increase in urine production

2. Penicillamine to increase cystine solubility

3. Decreased consumption of animal proteins and increased consumption of fruits/vegetables

4. Kidney transplant in extreme circumstances