2. Carbohydrate metabolism

Carbohydrate Metabolism

How Monosaccharides Enter Cells

Start with Glucose. Membranes have a low permeability to Glucose (more on this here).

permeation_through_pure_lipid_bilayer_w

To enter cells, they need transporters. One such transporter found in red blood cells is GLUT1.

GLUT1

  • passive transporter
  • moves glucose with the concentration gradient
  • not a channel: moves slower than expected for a passive transporter
  • stepwise transfer: GLUT1 opens on the extracellular side to accept the glucose, then closes, then opens on the cytosolic side to release the glucose.

Simple monosaccharides use GLUT transporters: glucose, galactose, and fructose

  • In RBCs: glucose and galactose but not fructose are transported by GLUT1.
  • In the liver: glucose, galactose, and fructose are all transported by GLUT2

Glycolysis for other Monosaccharides

For glucose, glycolysis is a linear pathway to pyruvate. Other monosaccharides enter at later points.

Galactose: similar structure of glucose, but no enzyme to catalyze the isomeration of galactose into glucose.

Galactose

The conversion of Galactose to G1P is indirect:

  1. Galactose -> Galactose-1P (costs: ATP)
  2. Galactose-1P + UDP-Glucose <–> UDP-Galactose + G1P
  3. G1P->G6P —- enters to Glycolysis
  4. UDP-Galactose (from #2) ->…-> UDP-Glucose (2 steps, each reducing NAD+)
Galactose entering glycolysis. From class lecture slide. All rights HarvardX/EdX.
Galactose entering glycolysis. From class lecture slide. All rights HarvardX/EdX.

So in glycolysis, net result for galactose is the investment of 1 ATP to produce G6P+ADP. The oxidation of Galactose into pyruvate is 4 ATP (consumes 2): net 2 ATP

Fructose: a bit more complicated and tissue-specific. F6P is a logical point of entry for Fructose, it would seem….

Hexokinase phosphorylates Fructose to F6P, but only in cells where the [Glu] is low. For example, adipocytes.

Adipocytes. Taken from class lecture slide. All rights HarvardX/EdX
Adipocytes. Taken from class lecture slide. All rights HarvardX/EdX

In contrast, in liver and muscle where [Glu] is high there’s not much chance this will happen. Here an enzyme called Fructokinase (tissue-specific) catalyzes Fructose into F1P (cost: 1 ATP). Aldolase then catalyzes the cleavage of F1P into Glyceraldehyde and Dihydroxyacetone phosphate (DHAP), of glycolysis fame. Glyceraldehyde can be phosphorylated into G3P (cost: 1 ATP), also of glycolysis fame.

So the use of Fructose in glycolysis leads to a net 2 ATP.

Polysaccharides (PS)

These undergo complete hydrolysis to release their MS components: Glucose, galactose, fructose, and mannose (which can be converted to F6P).

Dietary PS (starches) and Disaccharides (plants).

Digestion starts in the mouth with amylase catalyzing the hydrolysis of PS into smaller molecules called oligosaccharides.

Amylase gets nuked in the stomach (low pH).

The pancreas releases a second wave of amylase to continue digestion of oligosaccharides as food enters the small intense.

The next round of digestion produces disaccharides thanks to enzymes attached to the lumen-side of intestinal cells catalyzed the formation of MS. Sucrose, for example, into Glucose and Fructose via the bound enzyme sucrase.

The MS get absorbed by the intestine and distributed to tissues for glycolysis, et al.

Some complex carbs can not be digested by host enzyme. These require gut bacteria (gross!).

Most but not all dietary disaccharides come from plants.

digestion.
digestion. Taken from class lecture slide. All rights HarvardX/EdX

Degradation of Glycogen

This is a two-step process.

  1. Glycogen phosphorylase hydrolyzes glucose from the non-reducing end of the glycogen chain
  2. When a branch contains only 4 enzymes, the branching enzyme transfers 3 units from this short branch to the reducing end of a longer branch nearby. The same enzyme will hydrolyzes the single Glu that formed the branch point.

During synthesis of the glycogen, each new Glu unit consumes ATP when UDP-Glu is formed.

Glycogen is synthesized when Glu and ATP are abundant. When G1P is released during Glycogen breakdown, [Glu] and [ATP] are low.

When energy is needed, Glycogen is degraded to form G1P, not Glu. Thus the first step of Glycolysis is skipped, saving 1 ATP. This gives a net glycotic yield is 3 ATP instead of 2.

Branched and linear forms of starches are digested into Maltose units, a DS of 2 units of Glu.

 

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