Ch. 23 - Carbohydrate Metabolism

Digestion of Carbohydrates

• During carbohydrate digestion, di- and polysaccharides are hydrolyzed to monosaccharides

• After digestion, glucose, fructose, and galactose are absorbed into the bloodstream through the lining of the small intestine and transported to the liver

• In the liver, fructose and galactose are converted to glucose or metabolically similar compounds

Blood Glucose

Liver regulates the blood glucose level

• liver responds to increase in blood glucose after a meal by removing glucose from bloodstream

• Converts the removed glucose to glycogen or triglycerides

• Converts glycogen to glucose and synthesizes new glucose from noncarbohydrate substances when blood glucose levels are low

Blood Sugar Level

Amount of glucose present in blood

• expressed as mg glucose per 100 mL of blood

• Highest about 1 hour after a carb-containing meal

• Returns to normal after 2 to 2.5 hours

Hypoglycemia

Lower-than-normal blood sugar level

Hyperglycemia

Higher-than-normal blood sugar level

Renal Threshold

Blood sugar level at which sugar is not completely reabsorbed by the kidneys

• point at which glucose can be detected in urine

Glucosuria

Condition where elevated blood sugar levels result in the excretion of glucose in the urine

• Prolonged hyperglycemia at glucosuric levels is considered serious

Normal Fasting Level

70-110 mg/100 mL

Glycolysis

• Glucose is catabolically oxidized through a series of steps to pyruvate

• Occurs in the cellular cytoplasm

• Net reaction

  • glucose + 2P i + 2ADP + 2NAD+ → 2Pyruvate + 2ATP + 2NADH + 4H + + 2H2O

Regulation of Glycolysis

regulated by hexokinase, phosphofructokinase, and pyruvate kinase

• As glycolysis occurs, the citric acid cycle and electron transport chain produce large quantities of ATP

  • If the ATP level is low, then AMP and ADP levels are high

What inhibits hexokinase?

Glucose-6-phosphate noncompetitively inhibits hexokinase

• this is a feedback inhibition

What inhibits and what activates phosphofructokinase?

• inhibited by high concentrations of ATP and citrate

• Activated by high concentrations of ADP and AMP

What inhibits pyruvate kinase?

inhibited by high concentrations of ATP

Fates of Pyruvate

After glycolysis, pyruvate can be:

• Oxidized to acetyl CoA

• Reduced to lactate

• Reduced to ethanol

All processes must regenerate NAD+ from NADH so that glycolysis can continue

Oxidation of Pyruvate to Acetyl CoA

Occurs in the mitochondria under aerobic conditions

• Most of the acetyl CoA will be completely oxidized to CO2 in the CAC

• NAD+ is regenerated when NADH transfers its electrons to O₂ in the ETC

• Some acetyl CoA will serve as starting material for fatty acid biosynthesis

Reduction of Pyruvate to Lactate

Occurs in cells after strenuous or long-term muscle activity because the supply of oxygen is not enough for the reoxidation of NADH to NAD+

• Under anaerobic conditions, animals and some microorganisms can obtain limited energy through lactate formation

Reduction of Pyruvate to Ethanol

Under anaerobic conditions, some microorganisms can obtain limited energy through glycolysis

• Alcoholic fermentation: Conversion of glucose to ethanol

Only occurs in prokaryotes, not humans

Citric Acid Cycle (CAC)

Series of reactions in which acetyl CoA is oxidized to CO2 and FADH2 and NADH are formed

• Principal process for generating NADH and FADH2

• Source of materials for biosynthesis

• Occurs within the matrix of the mitochondrion

Features of the CAC

• Fueled by acetyl CoA

• Operation of the cycle depends on reactions of the ETC for the supply of NAD+ and FAD+

• 2 carbon atoms enter the cycle as an acetyl unit and 2 carbon atoms leave the cycle as 2 molecules of CO2

  • There is a one-cycle delay between the entry and exit of the atoms

• 4 oxidation–reduction reactions produce 3 NADH and 1 FADH2 in one complete cycle

• 1 guanosine triphosphate (GTP) is produced

Regulation of Citric Acid Cycle

Entry of acetyl CoA and rate of operation of the cycle are:

• Reduced when cellular ATP levels are high

• Stimulated when ATP supplies are low and ADP levels are high

Control Points in the CAC

Point 1

• Inhibited by ATP and NADH

• Activated by ADP

Point 2

• Inhibited by NADH

• Activated by ADP

Point 3

• Inhibited by succinyl CoA, NADH, and ATP

What compound is the starting compound AND ending compound in the CAC?

Oxaloacetate

Electron Transport Chain (ETC)

Series of reactions where protons and electrons from the oxidation of foods are used to reduce molecular oxygen to water

• NADH and FADH2 are produced by the citric acid cycle

  • Carry hydrogen ions and electrons during food oxidation

• Net equation

  • 4H+ + 4e - + O2 → 2H2O

• Electron carriers are lined up in order of increasing affinity for electrons

• First electron carrier is flavin mononucleotide (FMN)

  • Contains a tightly bound coenzyme, which has a structure similar to FAD

• Four electron carriers are cytochromes

Cytochromes

iron-containing enzymes

Oxidative Phosphorylation

Process coupled with the ETC whereby ADP is converted to ATP

• Helps conserve some free energy

  • a lot of free energy is released as electrons are transported along the ETC

Oxidation and phosphorylation reactions conserve approximately:

• 34% of the energy released from the electron transport chain for each mole of NADH

• 25% of the energy released from the electron transport chain for each mole of FADH2

Energy yield for the entire catabolic pathway:

(citric acid cycle, electron transport chain, and oxidative phosphorylation combined)

• 3 NADH produces 7.5 ATP

• 1 FADH 2 produces 1.5 ATP

• 1 GTP is equivalent to 1 ATP

10 ATP total produced

Chemiosmotic Hypothesis

States that a proton flow across the inner mitochondrial membrane during the operation of the ETC provides energy for ATP synthesis

Complete Oxidation of Glucose

Net Yield is 32 ATP

• NADH produced in the cytoplasm does not pass through the mitochondrial membrane to the site of the ETC

• Brain and muscle cells employ a transport mechanism that passes electrons from cytoplasmic NADH through the membrane to FAD molecules inside mitochondria

  • One molecule of cytoplasmic NADH generates only 1.5 molecules of ATP

• In liver, heart, and kidney, one molecule of mitochondrial NADH and 2.5 molecules ATP are generated for every cytoplasmic NADH

Glycogenesis

Synthesis of glycogen from glucose

• Glucose units bond to a growing glycogen chain

  • Hydrolysis of UTP provides energy

• Occurs in all cells but is especially important in liver and muscle cells

• Glycogen is mainly stored in liver and muscle tissue

Glycogenolysis

Breakdown of glycogen to glucose

• Occurs in the liver, kidney, and intestinal cells but not in the muscle tissue

• Muscle cells cannot form free glucose from glycogen

  • Can carry out the first 2 steps of glycogenolysis to produce glucose-6-phosphate for energy production

• Liver

  • Maintains a relatively constant level of blood glucose

  • Has the ability to break down glycogen to glucose, which is released into the blood during muscular activity and between meals

Steps of Glycogenolysis

Step 1:

• Cleavage of α(1→4) linkages is catalyzed by glycogen phosphorylase

Step 2 - Cleavage of α(1→6) linkages by hydrolysis

• Hydrolysis is carried out by a debranching enzyme

Step 3:

• Hydrolysis of glucose 6-phosphate

Gluconeogenesis

Synthesis of glucose from noncarbohydrate molecules

(lactate, certain amino acids, glycerol) → pyruvate → glucose

• Primarily occurs in the liver (90%)

• Helps maintain blood glucose level

• Occurs in the kidneys, brain, skeletal muscle, or heart in small amounts

Cori Cycle

Process where glucose is converted to lactate in muscle tissue, lactate is reconverted to glucose in liver, and glucose is returned to the muscle

During active exercise:

• Lactate levels increase in muscle tissue and the compound diffuses out of the tissue into the blood

• Lactate is taken to liver and converted back to pyruvate

• Pyruvate is converted to glucose by gluconeogenesis and glucose enters the blood and returns to the muscles

Hormones that Control Carbohydrate Metabolism

• Insulin

• Glucagon

• Epinephrine

Insulin in Carbohydrate Metabolism

Source - β-cells of pancreas

• Enhances the absorption of glucose from the blood into the cells of active tissue

• Increases the rate of synthesis of glycogen, fatty acids, and proteins

• stimulates glycolysis

• lowers blood glucose levels

Glucagon in Carbohydrate Metabolism

Source - α-cells of pancreas

• Increases blood glucose levels

• Activates the breakdown of glycogen in the liver

Epinephrine in Carbohydrate Metabolism

Source - Adrenal medulla

• increases blood glucose levels

• stimulates glycogen breakdown in muscles and liver

What does blood sugar level depend on?

it depends on the biochemical balance of insulin and glucagon

• this can be influenced by growth hormones and adrenal cortex steroids