Biochemistry: Metabolism Overview

Chapter Twenty Two: Metabolic Pathways for Carbohydrates

• Metabolic pathways provide energy and substances for continued cell growth
• Two types of metabolic reactions:
  • Catabolic reactions: break down complex molecules into smaller ones, releasing energy
  • Anabolic reactions: use energy to build larger molecules

Stages of Catabolism

• Catabolism is organized into stages:
  • Stage 1: Digestion and hydrolysis. Large polymers are broken down into monomers which then enter the bloodstream
  • Stage 2:Cellular degradation. Each set of molecules is broken down differently into two- and three-carbon compounds.
  • Stage 3: Oxidation. All the small molecules are oxidized in the citric acid cycle and electron transport to generate ATP energy.

Stages of Catabolism: From Digestion to Cell

• A diagram showing the stages of catabolism, including proteins, polysaccharides, lipids, and the conversion to ATP
• Breakdown of proteins into amino acids, polysaccharides into glucose, fructose, and galactose, lipids into fatty acids and entering cells
• Oxidation to CO₂, H₂O, and energy for ATP synthesis

ATP, Adenosine Triphosphate

• ATP is composed of adenine, a ribose sugar, and three phosphate groups
• Hydrolysis of ATP to ADP and AMP releases energy
• More phosphate groups mean more stored energy

ATP Drives Reactions

• Catabolic reactions release energy, storing it in ATP
• Anabolic reactions use energy from ATP hydrolysis
• 7.3 kcal/mole of energy (31 kJ/mole) is released when ATP is converted to ADP + P_i

Metabolic Reactions

• A coenzyme that gains hydrogen ions and electrons is reduced and energy is stored
• A coenzyme that loses hydrogen ions and electrons to a substrate is oxidized

Table 22.2: Characteristics of Oxidation and Reduction

• Oxidation: loss of electrons, loss of hydrogen (H or H⁺ and e⁻), gain of oxygen, and release of energy.
• Reduction: gain of electrons, gain of hydrogen (H or H⁺ and e⁻), loss of oxygen, and input of energy.

Structure of Coenzyme NAD+

• NAD+ is nicotinamide adenine dinucleotide
• Attached to a derivative of coenzyme niacin (vitamin B₃)
• Collects an H⁺ and 2 electrons

Coenzyme NAD+ or NADP+

• NAD+ is the oxidized form, NADH + H⁺ is the reduced form
• NAD+ collects 2H⁺ + 2e⁻ forming NADH + H⁺ (reduced form)
• NADPH is a derivative that collects H⁺ and 2e⁻

Coenzyme FAD

• FAD is flavin adenine dinucleotide
• Contains ADP and riboflavin (vitamin B₂)
• Collects 2H⁺ atoms (+ 2e⁻), reducing it to FADH₂

Structure of Coenzyme A

• Coenzyme A (CoA) is made up of pantothenic acid (vitamin B₅), phosphorylated ADP, and aminoethanethiol
• Preparation of small acetyl groups for enzyme reactions
• Production of the energy-rich thioester acetyl CoA

Function, Coenzyme A

• Preparation of small acyl groups (like acetyl) for reactions with enzymes
• Production of the energy-rich thioester acetyl CoA

Digestion of Carbohydrates

• Stage 1 of catabolism is digestion, the breakdown of food into small molecules
• In the mouth: physical grinding and mixing of food; chemical hydrolysis of carbohydrates
• α-amylase in saliva catalyzes hydrolysis of glycosidic bonds in carbohydrates
• Salivary α-amylase continues to act on polysaccharides in the stomach until denatured
• In the small intestine: further hydrolysis by pancreatic α-amylase, maltase, sucrase, and lactase
• Monosaccharides are absorbed into the bloodstream

Lactose Intolerance

• Lactase production may cease after childhood
• Lactose cannot be digested in the small intestine leading to fermentation
• Bacteria in the large intestine use lactose to form CO₂, H₂, and CH₄ causing cramps and diarrhea
• Milk products can be predigested with lactase enzyme

In The Cell Stage 2: Glycolysis

• Glucose from the bloodstream enters cells for decomposition
• Glucose (6C) is converted to 2 pyruvate (3C) through glycolysis (Stage 2 of catabolism).
• ATP input is returned when the process is completed.
• Glycolysis takes place in the cytosol of the cell

Glycolysis: Reaction 1

• Phosphorylation: a phosphate group is transferred from ATP to glucose, forming glucose-6-phosphate and ADP
• The enzyme hexokinase catalyzes this reaction

Glycolysis: Reaction 2

• Isomerization: Glucose-6-phosphate is converted to fructose-6-phosphate by the enzyme phosphoglucose isomerase

Glycolysis: Reaction 3

• Phosphorylation: fructose-6-phosphate is converted to fructose-1,6-bisphosphate by the enzyme phosphofructokinase

Glycolysis: Reaction 4

• Cleavage: fructose-1,6-bisphosphate is split into two three-carbon phosphate isomers (DHAP and G3P) by the enzyme aldolase

Glycolysis: Reaction 5

• Isomerization: dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate by the enzyme triose phosphate isomerase.

Glycolysis: Reaction 6

• Oxidation and phosphorylation: Glyceraldehyde-3-phosphate is oxidized to a 1,3-bisphosphoglycerate and NAD⁺ is reduced to NADH
• The enzyme glyceraldehyde-3-phosphate dehydrogenase catalyzes this reaction.

Glycolysis: Reaction 7

• Phosphate transfer: A phosphate group from 1,3-bisphosphoglycerate is transferred to ADP by phosphoglycerate kinase, forming ATP (x2).

Glycolysis: Reaction 8

• Isomerization: 3-phosphoglycerate is converted to 2-phosphoglycerate by the enzyme phosphoglycerate mutase

Glycolysis: Reaction 9

• Dehydration: 2-phosphoglycerate is converted to phosphoenolpyruvate by the enzyme enolase

Glycolysis: Reaction 10

• Phosphate transfer: A phosphate group from phosphoenolpyruvate is transferred to ADP by pyruvate kinase, forming ATP (x2)

Glycolysis: Overall Reaction

• Two ATP are used to phosphorylate glucose and fructose-6-phosphate
• Four ATP are produced from direct transfers of phosphate groups to ADP
• A net gain of 2 ATP and 2 NADH

Fructose and Galactose

• Galactose and fructose are intermediates in the glycolysis pathway
• They enter the pathway by forming glucose-6-phosphate or fructose-6-phosphate.

Regulation of Glycolysis

• Hexokinase is inhibited by high levels of glucose-6-phosphate
• Phosphofructokinase is inhibited by high levels of ATP and activated by high levels of AMP
• Pyruvate kinase is inhibited by high levels of ATP and acetyl CoA

Fates of Pyruvate

• Pyruvate can undergo fermentation or oxidation depending on oxygen availability.
• Under anaerobic conditions, pyruvate is converted to lactate
• Under aerobic conditions, pyruvate is converted to acetyl-CoA

Pyruvate: Anaerobic Conditions

• NADH concentration rises, reducing NAD⁺ availability
• Pyruvate is reduced to lactate by lactate dehydrogenase to regenerate NAD⁺
• Glycolysis can continue with a small amount of ATP produced.

Pyruvate: Aerobic Conditions

• Pyruvate moves to the mitochondria where it is oxidized to acetyl-CoA
• NAD⁺ is reduced to NADH to generate energy
• Acetyl-CoA enters the citric acid cycle, and NADH goes through the electron transport chain to produce ATP

Gluconeogenesis

• Glucose is produced from other substances (e.g., pyruvate, amino acids, glycerol) in gluconeogenesis
• Critical in fasting or starvation as the liver's glycogen stores become depleted
• The liver cells synthesize glucose for other cells

Glycolysis and Gluconeogenesis

• Glycolysis has 10 reactions
• Gluconeogenesis has 4 bypassed regulated reactions
• Key enzymes regulate both pathways, differing at specific points

Energy Cost of Gluconeogenesis

• Gluconeogenesis is costly, requiring 4 ATP, 2 GTP, and 2 NADH to synthesize one molecule of glucose.

Regulation of Blood Glucose

• Two pancreatic hormones, insulin and glucagon, regulate glucose levels
• Insulin lowers blood glucose by promoting glucose uptake into cells
• Glucagon raises blood glucose by signaling the liver to release stored glucose

Biochemistry of Extreme Activity

• The energy needed comes from ATP, creatine phosphate followed by glycolysis
• Oxygen is used at maximum capacity during extreme muscle exertion.
• Anaerobic glycolysis suffices until lactate buildup causes muscle fatigue

Biochemistry of Longer Exercise

• Oxygen supply in muscle tissues must be maintained for long-distance/time activity
• Aerobic glycolysis produces ATP as oxygen-carrying blood flows more quickly to muscles.
• Anaerobic threshold - Glycolysis and lactate recycling provide ATP when oxygen isn't sufficient.

Lactate and the Cori Cycle

• Lactate from muscles flows to the liver
• The liver converts pyruvate to glucose which is carried back to the muscles.

This quiz covers essential concepts in biochemistry related to metabolism, including ATP synthesis, catabolic reactions, and the roles of various coenzymes. Test your knowledge on how glucose is metabolized in different conditions and the biochemical reactions involved in energy production. Perfect for students studying biochemistry or related fields.