Biochemistry Lecture - Carbohydrates Metabolism

Reviewer for Carbohydrates Metabolism

Digestion

Breakdown of food molecules by hydrolysis into simpler chemical units that can be used by cells in their metabolic processes.

Carbohydrate Digestion

Begins in the mouth

Alpha-Amylase

Catalyzes the hydrolysis of alpha-glycosidic linkages of starch and glycogen to produce smaller polysaccharides and disaccharides (maltose).

Stomach

Very little carbohydrate is digested due to denaturation of enzymes (salivary amylase) from the acidic environment.

Small Intestine

The primary site for carbohydrate digestion.

Pancreatic Alpha-Amylase

Breaks down polysaccharide chains into disaccharide - maltose

Disaccharide Enzymes

Converts disaccharides (maltose, sucrose, and lactose) into monosaccharides (glucose, fructose, and galactose)

Maltase

Converts maltose to glucose

Sucrase

Converts sucrose to glucose and fructose

Lactase

Converts lactose to glucose and galactose

ATP Hydrolysis and Protein Carriers

Mediate the passage of the monosaccharides through cell membranes.

Live

Site where galactose and fructose are converted to products of glucose metabolism.

Phosphorylation of Glucose

Phosphate group from ATP is transferred to the hydroxyl group on carbon 6 of glucose. It is an endothermic reaction.

Hexokinase

The enzyme that catalyzes the phosphorylation of glucose to form glucose-6-phosphate in the first step of glycolysis.

Blood Sugar Level

Normal value around 70-110 mg/100 mL (fasting of 8-12 hours)

Glycolysis

The metabolic pathway by which glucose is converted into two molecules of pyruvate. Produces chemical energy int the form of ATP, as well as NADH-reduced coenzymes.

Cofactor

General Term. They are non-protein helpers that may be bound tightly to the enzyme as a permanent resident or may bind loosely and reversibly along with the substrate.

Coenzyme

Specific Term. If the cofactor is an organic molecule.

Magnesium

A cofactor required in phosphorylation

Formation of Glucose-6-Phosphate

Step 1. Phosphate group from ATP is transferred to the hydroxyl group on carbon 6 of glucose. Uses the enzyme hexokinase.

Formation of Fructose-6-Phosphate

Step 2. Glucose-6-phosphate is isomerized using the enzyme phosphoglucoisomerase.

Formation of Fructose 1,6-Biphosphate

Step 3. Further phosphorylation of fructose-6-phosphate. Uses enzyme phosphofructokinase.

Formation of Triose Phosphates

Step 4. C6 species is split into two C3 species (dihydroxyacetone phosphate and glyceraldehyde 3-phosphate). Uses the enzyme aldolase.

Isomerization of Triose Phosphates

Step 5. Dihydroxyacetone phosphate is isomerized to glyceraldehyde 3-phosphate.

Oxidation of Glycerate 3-Phosphate

Step 6. G-3-P dehydrogenase catalyzes oxidation and phosphorylation of G-3-P to form 1,3-biphosphate glycerate (1,3-BPG).

Formation of 3-Phosphoglycerate

Step 7. Diphosphate is converted back to monophosphate species. Produces ATP using the enzyme phosphoglycerokinase.

Formation of 2-Phosphoglycerate

Step 8. Isomerization of 3-phosphoglycerate to 2-phospholgycerate (phosphate group moved from C3 to C2). Uses the enzyme phosphoglyceromutase.

Formation of Phosphoenolpyruvate

Step 9. An alcohol dehydration reaction - results in another high-energy phosphate group containing compound. Uses the enzyme enolase.

Formation of Pyruvate

Step 10. High energy phosphate is transferred from phosphoenolpyruvate to ADP molecule to produce ATP and pyruvate. Uses enzyme pyruvate kinase.

Total ATP Molecules from One Glucose Molecule

2

Steps 1, 3, and 10

Control points for glycolysis.

Control Point: Step 1

Conversion of glucose to glucose 6-phosphate by hexokinase. Hexokinase inhibited by glucose 6-phosphate (feedback inhibition).

Control Point: Step 3

Fructose 6-phosphate converted to fructose 1,6-biphosphate by phosphofructokinase. High concentrations of ATP and citrate inhibit phosphofructokinase.

Control Point: Step 10

Conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase. Enzyme is inhibited by high ATP concentration.

Allosteric Enzymes

Pyruvate Kinase and Phosphofructokinase

Lactate Fermentation

AN enzymatic anaerobic reduction of pyruvate to lactate occurs mainly in muscles. Converts NADH to NAD+ for increased rate of glycolysis. Lactate is eventually converted back to pyruvate once aerobic conditions are reestablished in the cell.

Muscle Fatigue

Associated with strenuous physical activity is attributed to increased build-up of lactate.

Formation of Acetyl CoA

Under aerobic conditions, pyruvate is oxidized by pyruvate dehydrogenase complex.

ATP Production for the Complete Oxidation of Glucose

NADH produced during Step 6 of glycolysis cannot directly participate in the ETC because mitochondria are impermeable to NADH and NAD+.

Glycerol 3-phosphate-dihydroxyacetone phosphate

The transport system shuttles electrons from NADH, but not NADH itself, across the membrane.

30

Total ATP molecules Produced in Muscle and Nerve Cells.

26

Total ATP molecules from oxidative phosphorylation of ETC.

4

Total ATP molecules from oxidation of glucose to pyruvate, and from conversion of GTP to ATP.

Malate-Aspartate Shuttle

Found in other cells such as heart and liver cells. It is a more complex system that produces 32 ATP molecules instead of 30 molecules.

Glycogenesis

Metabolic pathway by which glycogen is synthesized from glucose.

Glycogenesis: Step 1

Formation of glucose 1-phosphate. Starting material is glucose 6-phosphate, enzyme phosphoglucomutase catalyzes the conversion.

Glycogenesis: Step 2

Formation of UDP Glucose. High energy compound UTP (uridine triphosphate) activates glucose 1-phosphate and uridine diphosphate glucose (UDP-glucose).

Glycogenesis: Step 3

Glucose transfer to a glycogen chain. The glucose unit of UDP-glucose is attached to the end of a glycogen chain and UDP is produced. UDP reacts with ATP to form UTP and ADP.

Energy Requirement for Glycogen

Adding one glucose unit to a glycogen chain requires the investment of two ATP molecules.

Glycogenolysis

Breakdown of glycogen to glucose-6-phosphate. It is not just reverse of glycogenesis because it does not require UTP or UDP molecules.

Glycogenolysis: Step 1

Phosphorylation of a glucose residue. Glycogen phosphorylase catalyzes the removal of an end glucose residue from a glycogen molecule as glucose 1-phosphate.

Glycogenolysis: Step 2

Glucose 1-phosphate isomerization. Phosphoglucomutase isomerizes glucose 1-phosphate to glucose 6-phosphate (reverse of the first step of glycogenesis).

Low Glucose Levels

Stimulates glycogenolysis in liver cells.

Gluconeogenesis

Metabolic pathway by which glucose is synthesized from non-carbohydrate sources. The process is not exact opposite of glycolysis. Helps maintain normal blood-glucose levels in times of inadequate dietary carbohydrate intake.

Noncarbohydrate Starting Materials for Gluconeogenesis

Pyruvate, lactate, glycerol, certain amino acids.

Gluconeogenesis Summary

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H2O -> Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+

Pentose Phosphate Pathway

A metabolic pathway in which glucose is used to produce NADPH ribose 5-phosphate (a pentose phosphate) and numerous other sugar phosphates. When ATP demand is high, the pathway continues to its end products which enter glycolysis. When NADPH demand is high, intermediates are recycled to glucose 6-phosphate (the start of the pathway), and further NADPH is produced. Helps generate ribose 5-phosphate for nucleic acid and coenzyme production.

Two Stages of PPP

Oxidative Stage and Nonoxidative Stage

Oxidative Stage of PPP

Involves three steps through which glucose 6-phosphate is converted to ribulose 5-phosphate and CO2.

Nonoxidative Stage of PPP

In the first step of nonoxidative stage of the PPP, ribulose 5-pohphate (ketose) is isomerized to ribose 5-phosphate (aldose).

Hormonal Control of Carbohydrate Metabolism

The second major method for controlling carbohydrate metabolism.

Three Major Hormones for Carbohydrate Metabolism

Insulin, Glucagon, Epinephrine

Insulin

Produced by beta cells of pancreas. 51 amino acid polypeptides. Promotes utilization of glucose by cells. Lowers blood glucose levels and is also involved in lipid metabolism. Release is triggered by high blood-glucose levels. Also produces an increase in the rate of glycogen synthesis.

Glucagon

29 amino acid peptide hormones. Produced in the pancreas by alpha cells. Released when blood glucose levels are low. Increases blood-glucose concentration by speeding up the conversion of glycogen to glucose (glycogenolysis) in the liver. Opposite of insulin.

Epinephrine

Also known as adrenaline. Released by the adrenal glands in response to anger, fear, or excitement. Function is similar to glucagon. Primarily targets muscle cells. Promotes energy generation for quick action. Also functions in lipid metabolism.

Cori Cycle

- The cycle of lactate to glucose between the muscle and liver
- Glucose is broken down into pyruvate, pyruvate is then reduced to lactate (to regenerate NAD+), lactate enters the bloodstream and into the liver, in the liver, lactate is converted back to pyruvate, pyruvate then undergoes gluconeogenesis to form glucose.
- Lactate -> Pyruvate -> Glucose.