Chapter 8: Energy Metabolism


What is Metabolism?

  • sum of all chemical reactions in the body

    • chemical reactions follow metabolic pathways where compounds are converted to new compounds

  • energy is stored in the bonds that connect the molecules that make up carbohydrates, proteins, and fats

  • energy is released when the bonds are broken. this occurs with:

    • aerobic (with oxygen) reactions

    • anaerobic (without oxygen) reactions

  • to meet the body’s constant energy supply, metabolism never stops

  • metabolic processes adapt to meet individual needs and the environment


Metabolism Takes Place Within Cells

  • different cells perform different metabolic functions

  • each cell’s structure is similar

    • outside of cell

      • plasma membrane: holds in the cell contents

    • inside of cell

      • organelles

        • mitochondria: generate most of the cell’s energy from carbohydrates, proteins, and fats

        • energy is generated by aerobic metabolism

      • cytosol

        • fluid portion of the cell

        • anaerobic metabolism


The Liver Plays a Central Role in Metabolism

  • the liver is the most metabolically active organ in the body

  • first organ to metabolize, store, and distribute nutrients after absorption

  • liver converts monosaccharides, amino acids, glycerol, and fatty acids:

    • into new compounds

    • into energy

    • or stores them for future use

      • triglycerides

      • glycogen


Metabolism is a Series of Chemical Reactions

  • metabolic pathways are sequences of reactions that comvery compounds from one form to another

  • anabolic reactions: absorb energy

    • combine simple molecules to form larger molecules

      • glucose → glycogen

      • amino acids → proteins

      • fatty acids and glycerol → triglycerides

  • catabolic reactions: release energy

    • break down large molecules to simple molecules

anabolic and catabolic reactions

Enzymes and Hormones Regulate Metabolism

  • enzymes allow chemical reactions of metabolism to occur at rate sufficient to maintain normal body function

  • coenzymes assist enzymes

  • hormones regulate anabolic and catabolic reactions


How Does ATP Fuel Metabolism?

  • before the body can use energy from food, it disassembles macronutrients into CO2 and H2O while capturing the released energy as adenosine triphosphate (ATP)

    • ATP: a high-energy molecule composed of adenine, ribose, and 3 phosphate molecules

    • any source of macronutrients can be used to generate ATP


ATP is the Cell’s Energy Currency

  • ATP is the cell’s direct energy source

  • energy is stored in the bonds that connect the phosphate groups

  • the body must continually produce ATP to provide a constant supply of energy

  • adenosine diphosphate (ADP)

    • formed when one phosphate molecule is removed from ATP

  • regenerating ATP from ADP requires a source of phosphate

  • sources

    • inorganic phosphate produced from initial breakdown of ATP

    • inorganic phosphate in creatine phosphate (aka phosphocreatine or PCr)

  • both sources provide enough ATP to sustain a sprint for up to 10 seconds

  • creatine phosphate

    • high-energy compound formed in muscle cells when creatine combines with phosphate

    • phosphate molecule is released to form ATP

  • as creatine phosphate levels dwindle, the body switches to anaerobic and aerobic metabolism to make ATP

  • anaerobic metabolism

    • produces less ATP per minute

    • only provides 1 to 1.5 minutes of maximal activity

    • involved in high-intensity, short-duration activities, such as sprinting and heavy weight lifting

  • aerobic metabolism

    • produces more ATP per minute

    • is able to produce ATP indefinitely

    • involved in low-intensity, long-duration activities

    • when demand for ATP is greater than the rate of metabolism, the activity slows down


How Do the Macronutrients Provide ATP?

  • carbohydrates, fats, and proteins enter the metabolic pathways at some point during the stages of metabolism

  • major metabolic pathways

    • glycolysis (stage 1)

    • pyruvate to acetyl Co A (stage 2)

    • TCA cycle (stage 3)

    • electron transport chain (stage 4)

metabolic fate of food

Glycolysis Transforms Glucose to Pyruvate

  • the first step in forming ATP from glucose begins with glycolysis

  • glucose metabolism is an essential energy source for all cells and particularly the brain and red blood cells

  • glycolysis is a 10-step anaerobic catabolic pathway that takes place in the cytosol of the cells

  • glycolysis takes place in the cytosol

    • begins with one 6-carbon glucose molecule

    • ends with two 3-carbon molecules of pyruvate and two net molecules of ATP

    • glycolysis also generates hydrogen ions

    • coenzymeNAD+ picks up hydrogen ions to form NADH

    • NADH carries hydrogen ions and electrons to the electron transport chain


Metabolism of Fructose and Galactose

  • the other monosaccharides can also be used to produce ATP

    • fructose enters glycolysis after going through seven metabolic steps

    • galactose enters after going through 4 metabolic steps

    • a specific enzyme directs each step of converting each monosaccharide into an intermediate substrate in glycolysis


glycolysis

Pyruvate to Lactate

  • metabolic conversion occurs in any cell in the body, including muscle

  • during anaerobic metabolism, pyruvate is reduced to lactate to prevent a buildup of excess hydrogen ions

  • lactate diffuses out of the cell and enters the liver

  • the liver converts lactate to glucose via the Cori cycle

Cori Cycle

Glycogenic Amino Acids to Pyruvate

  • 18 out of 20 amino acids are considered glucogenic

    • can be transformed into pyruvate and other TCA cycle intermediates that enter gluconeogenesis and produce glucose

    • pyruvate is the entry point into metabolism for 6 of these

      • alanine, serine, glycine, threonine, tryptophan, and cysteine

      • these glucogenic amino acids are a major source of blood glucose when the diet is lacking in carbohydrate

    • the other 12 glucogenic amino acids enter at points along the TCA cycle

glucogenic and ketogenic amino acid 
metabolism

Glycerol to Pyruvate

  • only the glycerol portion of the triglyceride is glucogenic and can be used to make glucose

  • glycerol produces very little energy compared with glucose, amino acids, or fatty acids


Glycolysis Summary

  • 10 step process that produces:

    • 2 molecules of ATP

    • 2 molecules of pyruvate

    • 2 coenzyme molecules

    • 2 hydrogen ions that are transported to the electron transport chain

    • 2 water molecules


Pyruvate is Transformed into Acetyl Co A

  • all energy- producing nutrients are transformed to acetyl Co A before entering the TCA cycle

  • occurs in the presence of oyxgen

  • 2 molecules of pyruvate cross the mitochondrial membrane and enter the mitochondria

    • a carbon molecule is removed and coenzyme A is added

  • Acetyl Co A can enter 2 pathways

    • TCA cycle (if ATP is limited)

    • converted to fatty acid and stored as fat (ample ATP)

the fate of pyruvate

Fatty Acids to Acetyl Co A

  • fatty acids are hydrolyzed from triglycerides by lipolysis before they can be used for enegry

    • hormone-sensitive lipase in the adipose tissue catalyzes the reaction

  • fatty acids must be activated before they cross into the mitochondria

  • the addition of coenzyme A to the carboxylic end of the fatty acid chain activates the fatty acid

fatty acids are oxidized for energy
  • inside the mitochondrion, fatty acids are disassembled by beta-oxidation

  • beta-oxidation steps:

    • two carbons at the end of the fatty acid are removed and joined with Co A to form acetyl Co A

    • this process continues until all carbon molecules are converted

    • hydrogen and electrons are released as each pair of carbons is cleaved off

  • fatty acids are ketogenic

    • they can be used to form ketone bodies



Amino Acids to Acetyl Co A

  • ketogenic amino acids

    • leucine

    • lysine

  • both ketogenic and glucogenic amino acids

    • isoleucine

    • tryptophan

    • phenylalanine

    • tyrosine

  • both ketogenic and glucogenic amino acids are transformed to acetyl Co A before they enter the energy pathway


The Tricarboxylic Acid (TCA) Cycle Releases High-Energy Electrons and Hydrogen Ions

  • the TCA (ot citric acid or Krebs) cycle is the third stage for the oxidation of acetyl Co A

  • location is in the mitochondria

  • these macronutrients enter the cycle as acetyl Co A, where most of the energy in the original molecule is now trapped

    • this stored energy is freed during the TCA cycle and is transferred to two coenzyme hydrogen ion carriers to be released in the electron transport chain

  • one molecule of acetyl Co A enters the TCA cycle at a time

  • for every acetyl Co A that enters the cycle, 2 carbons are lost as CO2

  • 3 NADH + H+ and 1 FADH2 are made during each turn of the cycle

TCA Cycle

The Electron Transport Chain and Oxidative Phosphorylation Produces the Majority of ATP

  • comprised of a series of protein complexes located in the inner mitochondrial membrane

  • makes 90% of the ATP used by the body for energy, growth, and maintenance

  • electrons are transferred from one protein complex to another, resulting in the formation of ATP and water

    • protein complexes are called flavoproteins

      • contain riboflavin and cytochromes

      • cytochromes contain iron and copper

  • though vitamins and minerals do not provide energy, they are essential for energy production

electron transport chainenergy metabolism

How Does Metabolism Change during the Absorptive and Postabsorptive States?

  • absorptive state

    • period within 4 hours following a meal in which anabolic processes exceed catabolic processes

  • postabsorptive state

    • period of time usually more than 4 hours after eating

    • energy needs are met by the breakdown of stores

  • both are regulated by hormones

metabolism during the absorptive state

Carbohydrates are Stored as Glycogen

  • red blood cells and the central nervous system use glucose for energy

    • cannot store glucose

  • liver and muscle convert excess glucose into glycogen

  • liver glycogen

    • important to maintain blood glucose homeostasis

    • only glucose from liver glycogen can enter the bloodstream

    • depleted 12 to 18 hours after eating

  • muscle glycogen

    • used by muscle for energy


Excess Carbohydrates and Amino Acids are Stored as Triglycerides

  • excess glucose that is not stored as glycogen is converted into triglycerides

  • 25% of energy is spent to convert glucose to triglycerides

    • amino acids undergo deamination and remaining carbons are converted to acetyl Co A and then into fatty acids


Fatty Acids are Stored as Triglycerides

  • excess kilocalories in any form will be stored as a triglyceride via lipogenesis

  • 5% of energy is spent to convert fatty acids to triglycerides

  • dietary fat is easier to store as a triglyceride than dietary carbohydrate or protein

  • glucagon promotes lipolysis

  • insulin promotes fatty acid synthesis and inhibits lipolysis


During the Postabsorptive State, Metabolism Favors Energy Production

  • 4 or more hours after eating, the body meets energy needs from stored energy

  • stores are depleted during fasting

    • between meals and overnight

      • energy is from glycogen and fatty acids

    • after 18 hours, the body adapts

      • proteins, glycerol, pyruvate, and lactate are used to make glucose

      • lipolysis is increased

  • stores are depleted during fasting

  • prolonged fasting

    • ketone bodies provide energy to the brain

  • severe fasting or starvation

    • fat reservation

    • muscle tissue is broken down to provide energy


metabolism during the postabsorptive state

Ketogenesis Generates Energy During Prolonged Fasting

  • ketogenesis is the formation of ketone bodies

    • occurs with the buildup of acetyl Co A

    • peaks after an individual has fasted or consumed a limited-carbohydrate diet for 3 days

  • as the fast continues the brain uses ketones for fuel

    • 30% of fuel is from ketones, with 70% from blood glucose

  • ketoacidosis is the excess accumulation of ketone bodies

    • occurs with untreated type 1 diabetes

    • can lead to impaired heart activity, coma, and even death

the formation of ketone bodies

How Does the Body Metabolize Alcohol?

  • alcohol

    • contains 7 kilocalories per gram

    • absorbed directly through the stomach mucosa and intestinal lining

    • metabolized by the liver, about half an ounce per 1.5 hours

    • excess alcohol circulates throughout the body until the liver enzymes can break it down


The Enzymes that Metabolize Ethanol

  • alcohol is metabolized through 3 distinct pathways

    • alcohol dehydrogenase (ADH)

      • present in the stomach and liver

      • converts alcohol to acetyl Co A

        • used to produce energy in TCA cycle

        • converted into fatty acids and stored as a triglyceride

      • microsomal ethanol oxidizing system (MEOS)

        • used during chronic alcohol consumption

        • also metabolizes drugs

      • brain

        • catalase oxidizes alcohol to acetaldehyde

        • may be responsible for psychological effects


Excess Alcohol is Stored as Fat

  • fat metabolism is favored after alcohol consumption

  • fewer fatty acids are used for energy when alcohol is consumed

  • excess alcohol kilocalories are stored as fatty acids in adipose tissue and the liver

  • alcoholics will have fat deposits in their liver

    • can lead to cirrhosis

    • fat begins to accumulate in the liver after a single bout of drinking


What are Inborn Errors of Metabolism?

  • genetic conditions in which an individual lacks an enzyme that controls a specific metabolic pathway

  • results in the buildup of toxins

  • cannot be cured

  • can be controlled through diet


Phenylketonuria (PKU)

  • body is unable to metabolize phenylalanine because the enzyme phenylalanine hydroxylase is lacking

  • severe form

    • can lead to behavioral problems or mental retardation

  • mild to moderate conditions

    • prevented by following a prescribed controlled diet

  • treatment

    • limit intake of phenylalanine

    • maintain adequate intake of tyrosine, energy, and protein

    • avoid foods and beverages with aspartame


Maple Syrup Urine Disease (MSUD)

  • body is unable to metabolize branched-chain amino acids

    • leucine, isoleucine, and valine

  • untreated can lead to seizures, coma, and death

  • treatment

    • consume specially designed formulas

    • avoid products like beef, chicken, fish, eggs, nuts, and legumes


Homocystinuria

  • body is unable to convert homocysteine to cystathione

  • treatment

    • diet low in the amino acid methionine

    • supplement with B vitamins: folate, vitamin B6, and vitamin B12


Galactosemia and Glycogen Storage Disease

  • galactosemia

    • body is unable to convert galactose to glucose

    • treatment

      • avoid dietary lactose and galactose

  • glycogen storage disease

    • body is unable to break down glycogen and provide glucose to the muscle or body

  • treatment

    • avoid foods with sucrose, lactose, galactose, and fructose