Porth's Essentials of Pathophysiology, 4e

9

Cell Structure and Function

C h a p t e r 1

NH 2

N

N

High-energy bonds

Adenine

H

H

N

N

O

O

O

CH 2

O -

OP

OP

OP

A P P

P

ATP

O

O -

O -

O -

Nutrient metabolism

Energy used

H

H

H

H

OH OH

A

A P P

B

Ribose sugar

ADP

FIGURE 1-8. Adenosine triphosphate (ATP) is the major source of cellular energy. (A) Each molecule of ATP contains two high-energy bonds, each containing about 12 kcal of potential energy. (B) The high-energy ATP bonds are in constant flux.They are generated by substrate (glucose, amino acid, and fat) metabolism and are consumed as the energy is expended. ADP, adenosine diphosphate.

acid is reversible, and once the oxygen supply has been restored, lactic acid is converted back to pyruvic acid and used directly for energy or to synthesize glucose.

diphosphate (ADP) with the loss of one high-energy bond and to adenosine monophosphate (AMP) with the loss of two such bonds. The energy liberated from the hydrolysis of ATP is used to drive reactions that require free energy, such as muscle contraction and active trans- port mechanisms. Energy from foodstuffs is used to con- vert ADP back to ATP. Hence ATP is often called the energy currency of the cell; energy can be “saved” or “spent” using ATP as an exchange currency. Two types of energy production are present in the cell: the anaerobic (i.e., without oxygen) glycolytic path- way, occurring in the cytoplasm, and the aerobic (i.e., with oxygen) pathway, occurring in the mitochondria. The glycolytic pathway serves as the prelude to the aero- bic pathway. Anaerobic Metabolism Glycolysis is the anaerobic process by which energy is liberated from glucose. It is an important source of energy for cells that lack mitochondria. The process also provides a temporary source of energy for cells that are deprived of an adequate supply of oxygen. Glycolysis involves a sequence of reactions that convert glucose to pyruvic acid, with the concomitant production of ATP from ADP. The net gain of energy from the glycolytic metabolism of one molecule of glucose is two ATP mol- ecules. Although relatively inefficient as to energy yield, the glycolytic pathway is important during periods of decreased oxygen delivery, such as occurs in skeletal muscle during the first few minutes of exercise. Glycolysis requires the presence of nicotinamide adenine dinucleotide (NAD + ), a hydrogen carrier. The end products of glycolysis are pyruvate and NADH (the reduced form of NAD + ) plus H + . When oxygen is pres- ent, pyruvic acid moves into the aerobic mitochondrial pathway, and NAD + is regenerated as NADH delivers its electron and proton (H + ) to the oxidative electron transport system. Under anaerobic conditions, such as cardiac arrest or circulatory shock, pyruvic acid is con- verted to lactic acid, which diffuses out of the cells into the extracellular fluid. Conversion of pyruvate to lactic

Aerobic Metabolism Aerobic metabolism, which supplies 90% of the body’s energy needs, occurs in the cell’smitochondria and requires oxygen. It is here that the hydrogen and carbon molecules from dietary fats, proteins, and carbohydrates are broken down and combined with molecular oxygen to form car- bon dioxide and water as energy is released. Unlike lactic acid, which is an end product of anaerobic metabolism, carbon dioxide and water are relatively harmless and eas- ily eliminated from the body. In a 24-hour period, oxida- tive metabolism produces 150 to 300 mL of water. The citric acid cycle, sometimes called the tricar- boxylic acid (TCA) or Krebs cycle, provides the final common pathway for the metabolism of nutrients. In the citric acid cycle, which takes place in the matrix of the mitochondria, an activated two-carbon molecule of acetyl-coenzyme A (acetyl-CoA) condenses with a four-carbon molecule of oxaloacetic acid and moves through a series of enzyme-mediated steps. This pro- cess produces hydrogen atoms and carbon dioxide. As hydrogen is generated, it combines with NAD + or flavin adenine dinucleotide (FAD) for transfer to the electron transport system. Besides pyruvate from the glycolysis of glucose, products of amino acid and fatty acid degradation enter the citric acid cycle and contribute to the generation of ATP. Oxidation of electrons from the hydrogen atoms generated during glycolysis and the citric acid cycle takes place in the electron transport system located on the inner mitochondrial membrane. The elec- trons are used to reduce elemental oxygen, which combines with hydrogen to form water. During this sequence of oxidative reactions, large amounts of energy are released and used to convert ADP to ATP. Because the formation of ATP involves the addition of a high-energy phosphate bond to ADP, the process is called oxidative phosphorylation .

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