Biochemistry Glucose Transport

What are the two major families of glucose transporters?

GLUT (glucose transporters) and SGLT (sodium-glucose linked transporters).

How do GLUT transporters move glucose?

By facilitated diffusion.

Does GLUT-mediated glucose transport require energy?

No. GLUT transporters use facilitated diffusion and do not directly consume energy.

How does a GLUT transporter move glucose into a cell?

Glucose binds the membrane transporter, the transporter changes conformation, and glucose is released into the cytoplasm.

How many GLUTs have been described?

14 GLUTs.

Where is GLUT1 expressed?

All cell types; it is most highly expressed in erythrocytes, brain, and placenta.

What is the primary function of GLUT1?

Basal glucose uptake.

Is GLUT1 insulin-dependent?

No.

How does GLUT1 membrane expression respond to blood glucose?

Expression increases when blood glucose is reduced and decreases when glucose levels increase.

Where is GLUT2 found?

Hepatocytes, pancreatic β-cells, renal epithelial cells, and small intestinal epithelial cells.

Is GLUT2 unidirectional or bidirectional?

Bidirectional.

What sugars can GLUT2 transport from the intestine into portal circulation?

Glucose, galactose, and fructose.

What can GLUT2 allow hepatocytes to do with glucose?

Glucose can enter or exit hepatocytes.

Is GLUT2 insulin-dependent?

No.

What is GLUT3 also called?

The neuronal GLUT.

Where is GLUT3 primarily found?

Neurons.

What other cells express GLUT3?

Embryos, sperm, leukocytes, and some cancer cells.

Is GLUT3 insulin-dependent?

No.

How does GLUT3 compare with GLUT1, GLUT2, and GLUT4 in glucose affinity and transport capacity?

GLUT3 has higher glucose affinity and transport capacity.

What is the key characteristic of GLUT4?

It is the key insulin-dependent glucose transporter.

Where is GLUT4 found?

Adipocytes, skeletal muscle cells, and cardiac muscle cells.

What does insulin do to GLUT4?

Insulin stimulates translocation of GLUT4 to the cell membrane.

What are the two major sodium-dependent glucose transporters?

SGLT1 and SGLT2.

Are SGLT1 and SGLT2 insulin-dependent?

No. They are insulin-independent.

What drives glucose transport through SGLTs?

The sodium (Na⁺) concentration gradient.

Why is there a sodium gradient across the cell membrane?

Intracellular Na⁺ is much lower than extracellular Na⁺.

What maintains the Na⁺ gradient used by SGLTs?

The Na⁺/K⁺ ATPase pump.

How are Na⁺ and glucose transported by SGLTs?

They are transported together by symport.

What allows SGLTs to move glucose against its concentration gradient?

The energy stored in the Na⁺ concentration gradient.

Where are SGLT1 and SGLT2 expressed in the kidney?

In the renal tubular epithelium of the proximal tubule.

Where is SGLT1 found outside the kidney?

The brush border epithelium of the small intestine.

What is SGLT1's intestinal function?

Uptake of glucose and galactose from the small intestine.

Where is SGLT2 found?

Only in the kidney.

What is the renal role of SGLT1 and SGLT2?

They resorb glucose from the glomerular filtrate.

What normally happens to filtered glucose before urine leaves the kidney?

Virtually all glucose is resorbed.

What happens to glucose reabsorption at very high blood glucose levels?

The transporters cannot resorb all filtered glucose, resulting in glucosuria.

What is glucosuria?

Glucose spilling into the urine.

How can SGLT2 inhibitors decrease blood glucose?

They inhibit SGLT2, causing more glucose to be spilled into the urine.

How does an SGLT2 inhibitor interact with SGLT2?

It competitively inhibits the glucose-binding site of SGLT2.

Why doesn't glucose simply diffuse back out of cells through GLUT2?

Glucose is phosphorylated to glucose-6-phosphate, which is not transported by GLUT2.

What is glucose trapping?

Phosphorylation of glucose to glucose-6-phosphate (G-6-P), preventing it from leaving the cell through GLUT2.

Which enzymes phosphorylate glucose to glucose-6-phosphate?

Hexokinase and glucokinase.

What happens to ATP during glucose phosphorylation?

ATP is converted to ADP.

Can glucose-6-phosphate cross the GLUT2 transporter?

No.

What are two major fates of phosphorylated glucose?

It can be used to synthesize glycogen or enter glycolysis.

Why is glucose phosphorylation important for glycolysis?

It is the first step of glycolysis.

Where is hexokinase found?

In most mammalian cells.

What is the Km of hexokinase?

Low Km.

What does a low Km mean for hexokinase?

High affinity for glucose; it works efficiently at low glucose concentrations.

What inhibits hexokinase?

Glucose-6-phosphate strongly inhibits it.

Can hexokinase phosphorylate fructose?

Yes, but at a slower rate.

Is hexokinase regulated by insulin?

No.

Where is glucokinase found?

In the liver and pancreatic β-cells.

What is the role of glucokinase in the liver?

Helps process glucose for glycogen production.

What is the role of glucokinase in pancreatic β-cells?

Glucose sensing.

How does glucokinase's affinity for glucose compare with hexokinase?

Glucokinase has lower affinity for glucose than hexokinase.

Is glucokinase inhibited by glucose-6-phosphate?

No.

What type of reaction is glucokinase described as when it is not inhibited by G-6-P?

A supply-driven reaction.

How do glucokinase levels respond to blood glucose?

They rise and fall with blood glucose concentration.

What does insulin do to glucokinase transcription?

Insulin increases glucokinase transcription.

What does glucagon do to glucokinase transcription?

Glucagon decreases glucokinase transcription.

What is the major difference between hexokinase and glucokinase?

Hexokinase has high glucose affinity and is inhibited by G-6-P, whereas glucokinase has lower glucose affinity and is not inhibited by G-6-P.

Which enzyme works efficiently when glucose concentrations are low?

Hexokinase.

Which enzyme responds to elevated blood glucose?

Glucokinase.

Which enzyme is found in pancreatic β-cells for glucose sensing?

Glucokinase.

Which enzyme is strongly inhibited by G-6-P?

Hexokinase.

Which enzyme is not inhibited by G-6-P?

Glucokinase.

Which enzyme is stimulated at the transcriptional level by insulin?

Glucokinase.

Which animals lack hepatic glucokinase?

Ruminants and strict carnivores.

Why do ruminants lack hepatic glucokinase?

They obtain little dietary glucose and generate short-chain fatty acids from plant material.

Why do strict carnivores lack hepatic glucokinase?

They consume diets high in protein and low in carbohydrates.

Do ruminants and strict carnivores have pancreatic glucokinase?

Yes, for glucose sensing.

What does glucose-6-phosphatase (G6Pase) do?

Removes the phosphate from glucose-6-phosphate.

Where is G6Pase found?

Hepatocytes and intestinal and renal cells.

What does insulin do to G6Pase expression?

Insulin suppresses G6Pase expression.

Why is G6Pase important in hepatocytes?

It allows glucose to be released from hepatocytes through GLUT2.

Which cells lack G6Pase?

Muscle cells and adipocytes.

Why can't muscle cells and adipocytes export free glucose?

They lack glucose-6-phosphatase.

What is glycogen?

The storage form of carbohydrates/glucose in animals.

What is glycogen made of?

Glucose.

How many glucose residues can one glycogen molecule contain?

Up to approximately 30,000 glucose residues.

Where is glycogen located within cells?

In the cytosol.

Which tissues contain most of the body's glycogen?

Myocytes and hepatocytes.

What percentage of glycogen is water?

Glycogen is approximately 65% water.

What does glycogenesis mean?

Formation of glycogen.

What does glycogenolysis mean?

Breakdown/mobilization of glycogen.

What are the first steps of glycogen synthesis?

Glucose is phosphorylated to G-6-P, then G-6-P is converted to G-1-P.

Which enzymes phosphorylate glucose during glycogen synthesis?

Hexokinase and glucokinase.

What enzyme converts glucose-6-phosphate to glucose-1-phosphate?

Phosphoglucomutase.

What cofactor does phosphoglucomutase require?

Mg²⁺.

What is the next step after formation of glucose-1-phosphate in glycogen synthesis?

Glucose-1-phosphate is converted to UDP-glucose.

What enzyme synthesizes UDP-glucose?

UDP-glucose pyrophosphorylase.

What substrates are used to form UDP-glucose?

Glucose-1-phosphate and UTP.

What is the reaction for UDP-glucose formation?

G-1-P + UTP → UDP-glucose.

What are three possible fates of UDP-glucose?

Glycogen synthesis, the uronic acid pathway, and lactose synthesis in the mammary gland.

What is glycogenin?

An enzyme that catalyzes polymerization of the first few glucose molecules to form an oligosaccharide.

How many glucose molecules are initially added by glycogenin?

Approximately 3–15 glucose molecules.

What is the role of glycogenin in glycogen synthesis?

It forms the protein core of the glycogen complex and initiates the glycogen chain.

What enzyme elongates glycogen chains?

Glycogen synthase.

What does glycogen synthase add to glycogen?

Glucose molecules from UDP-glucose.