Cellular Metabolism and Energetics

Nutrients

• Nutrients are essential elements and molecules required by the body

Metabolic Activity

• Metabolic activity involves breaking down organic molecules to obtain energy
• The energy is stored as ATP
• ATP is then utilized to build new organic molecules

Energetics

• Energetics studies how the body balances heat gains and losses

Cell Requirements

• Cells require oxygen and nutrients to carry out reactions
• These nutrients include water, vitamins, mineral ions, and organic substrates

Metabolism

• Metabolism encompasses all chemical and physical changes occurring in body tissues
• It consists of catabolism and anabolism

Nutrient Pool

• Nutrient pool refers to all available nutrient molecules distributed in blood

Catabolism

• Catabolism converts large molecules into smaller ones
• It breaks down organic substrates and releases energy, which is used to synthesize ATP

Anabolism

• Anabolism converts small molecules into larger ones
• It is the synthesis of new organic compounds, creating new chemical bonds
• Anabolism functions include structural maintenance, repairs, growth, secretions, and nutrient reserves

Nutrient Reserves

• Triglycerides are the most abundant storage lipids, consisting primarily of fatty acids
• Glycogen is the most abundant storage carbohydrate, a branched chain of glucose molecules
• Proteins are the most abundant organic components in the body and perform many vital cellular functions

Energetics Study

• Energetics is the study of energy flow and its change from one form to another

Oxidation and Reduction Reactions

• Oxidation and reduction reactions are always paired
• Oxidation involves the loss of hydrogen or electrons, with the electron donor being oxidized
• Reduction involves the gain of hydrogen or electrons, with the electron recipient being reduced

Electron Energy

• Electrons carry chemical energy
• In a redox reaction, the reduced atom or molecule gains energy, while the oxidized atom or molecule loses energy
• Some energy is released as heat, and the remaining energy can perform physical or chemical work, like forming ATP

Electron Transport Chain

• The electron transport chain includes a series of protein complexes in mitochondria
• Electrons pass through a series of oxidation-reduction reactions
• Electrons are ultimately transferred to oxygen, forming water as they combine with oxygen atoms and hydrogen ions

Role of Coenzymes

• Coenzymes play a key role in the flow of energy within a cell
• They act as intermediaries, accepting electrons from one molecule and transferring them to another
• Examples of coenzymes are NAD and FAD, which remove hydrogen atoms from organic molecules

Hydrogen Atom

• Each hydrogen atom consists of an electron and a proton
• A coenzyme is reduced by accepting a hydrogen atom

Coenzyme FAD

• Coenzyme FAD accepts 2 hydrogen atoms, gaining 2 electrons, to form FADH2.

Coenzyme NAD

• Coenzyme NAD has a positive charge, denoted as NAD+ in its oxidized form
• It accepts 2 hydrogen atoms, gaining 2 electrons and releases 1 proton, which forms NADH.

Carbohydrate Catabolism

• Carbohydrate catabolism generates ATP and other high-energy compounds
• Cellular respiration involves glucose combining with oxygen to produce carbon dioxide and water and involves glycolysis, the citric acid cycle, and the electron transport chain
• One molecule of glucose provides a net gain of 30–32 molecules of ATP

Glycolysis

• Glycolysis breaks glucose in cytosol into smaller molecules that the mitochondria can use
• Glycolysis does not require oxygen, so it is an anaerobic reaction
• Glycolysis breaks a 6-carbon glucose molecule into two 3-carbon molecules of pyruvic acid (pyruvate)
• Glycolysis begins when an enzyme phosphorylates a glucose molecule, creating glucose-6-phosphate

Glycolysis Requirements

• Glycolysis requires glucose molecules, cytosolic enzymes, ATP/ADP, inorganic phosphate groups, and NAD (coenzyme)

Aerobic Metabolism

• Aerobic metabolism occurs within mitochondria
• It requires oxygen
• Energy released from the breakdown of pyruvate is used to produce a large amount of ATP
• It involves the citric acid cycle and the electron transport chain

Mitochondrial Membranes

• The outer mitochondrial membrane contains large pores and is permeable to ions and small organic molecules like pyruvate
• The inner mitochondrial membrane contains a carrier protein that moves pyruvate into the mitochondrial matrix
• The intermembrane space separates the outer and inner membranes

Citric Acid Cycle

• H atoms of pyruvate are removed by coenzymes and are the primary source of energy gain
• C and O atoms are removed and released as CO2 in decarboxylation
• Pyruvate interacts with NAD and coenzyme A (CoA) in the mitochondrion
• This interaction produces 1 CO2, 1 NADH, and 1 acetyl-CoA (acetyl group bound to CoA)

Acetyl Group

• The acetyl group transfers from acetyl-CoA to a 4-carbon oxaloacetate molecule, producing 6-carbon citric acid
• CoA is released to bind another acetyl group
• One citric acid cycle removes two carbon atoms
• This process regenerates the 4-carbon chain
• Multiple steps involve more than one reaction or enzyme
• H2O molecules are tied up in two steps

GTP Production

• One citric acid cycle produces one molecule of GTP (guanosine triphosphate) through substrate-level phosphorylation

Citric Acid Cycle Summary

• The citric acid cycle can be summarized as follows: CH3CO - CoA + 3NAD + FAD + GDP + Pi + 2H2O → CoA + 2CO2 + 3NADH + FADH2 + 2H+ + GTP

Oxidative Phosphorylation

• Oxidative phosphorylation involves the generation of ATP through the transfer of electrons from NADH and FADH2 to oxygen
• This occurs by a sequence of electron carriers within mitochondria
• It produces over 90 percent of the ATP used by the body
• The basis of the reaction is the formation of water: 2H2 + O2 → 2H2O

ETC

• The electron transport chain (ETC) consists of protein complexes in the inner mitochondrial membrane
• The key reactions of oxidative phosphorylation occur here
• There are four respiratory protein complexes, coenzyme Q, and electron carriers (cytochrome molecules)
• Each cytochrome has two parts: a pigment (containing a metal ion) and a protein (surrounding the pigment)

ATP

• Oxidative phosphorylation provides about 95% of the ATP needed to keep cells alive
• It requires oxygen and electrons
• Availability limits the rate of ATP generation
• Cells obtain oxygen by diffusion from extracellular fluid

Glycolysis

• Main method of ATP generation for most cells
• Reaction pathway starts with glucose
• Ends with carbon dioxide and water

Glucose Molecule Breakdown

• One glucose molecule during glycolysis is broken down anaerobically into 2 pyruvate molecules
• A cell gains a net 2 molecules of ATP
• 2 molecules of NADH pass electrons to FAD: -By an intermediate electron carrier in intermembrane space and then to ETC

Citric Acid Cycle:

• It takes two revolutions to break down 2 pyruvate molecules, with each revolution yielding 1 ATP by GTP
• Additional gain of 2 molecules of ATP happens
• H atoms are transferred to NADH and FADH2
• Coenzymes provide electrons to the electron transport chain

ETC

• In the electron transport chain (ETC), for each molecule of glucose, 10 NADH and 2 FADH2 deliver electrons
• Each NADH yields 2.5 ATP
  • Each of the 8 NADH from the citric acid cycle yields 2.5 ATP and 1 water molecule
• Each FADH2 yields 1.5 ATP
  • 2 FADH2 from glycolysis yield 3 ATP and 2 water molecules
• Total yield from the ETC is 23 ATP

ATP

• For each glucose molecule processed, a cell gains 30–32 molecules of ATP
• 2 ATP from glycolysis, 3–5 from NADH from glycolysis, 2 from citric acid cycle (by means of GTP), and 23 from ETC All but 2 ATP are produced in the mitochondria

Gluconeogenesis

• Synthesis of glucose from noncarbohydrate molecules takes place
• 3-carbon molecules other than pyruvate participates
• Glucose is stored as glycogen in the liver and skeletal muscle

Glycogenesis

• Formation of glycogen from excess glucose
• This formation involves several steps
• Requires high-energy compound uridine triphosphate (UTP)

Glycogenolysis

• Breakdown of glycogen to glucose monomers
• This occurs quickly
• Involves a single enzymatic step

Lipids

• Lipids contain carbon, hydrogen, and oxygen, but in different proportions than carbohydrates
• Triglycerides are the most abundant lipid in the body

Lipid Catabolism (Lipolysis)

• Breaks lipids down into smaller pieces that can be:
  • Converted to pyruvate
  • Channeled directly into the citric acid cycle
• Hydrolysis splits a triglyceride into the component parts
  • 1 molecule of glycerol
  • 3 fatty acid molecules
• Enzymes in the cytosol convert glycerol to pyruvate
  • Pyruvate is converted to acetyl-CoA and it enters citric acid cycle

Lipid and Energy

• A cell can gain 120 ATP from the breakdown of one 18-carbon fatty acid molecule
  • Almost 1.3 times the energy gained from the breakdown of three 6-carbon glucose molecules

Lipid Synthesis (Lipogenesis)

• It can use almost any organic substrate
  • Lipids, amino acids, and carbohydrates can be converted to acetyl-CoA
• Glycerol:
  • Synthesized from dihydroxyacetone phosphate
  • This reaction is an intermediate product of glycolysis and gluconeogenesis

Lipid Synthesis: Production

• Nonessential fatty acids and steroids can be synthesized from acetyl-CoA
• Essential fatty acids:
  • The are acids the body cannot synthesize
  • Must be consumed
  • Ex: linoleic acid and linolenic acid, specifically 18-carbon unsaturated fatty acids usually found in plants

Lipid Storage

• Provides important energy reserves
• Large amounts of ATP, but slowly
• Difficult for water-soluble enzymes to reach

Lipid Transport and Distribution

• Is important because:
  • Cells require lipids to maintain plasma membranes
  • Steroid hormones must reach target cells in many different tissues

Lipid Insoluble

• Because most lipids are not soluble in water, then special transport mechanisms are needed to carry the lipids from one region to another

Fat Transport

• Most lipids are fats that circulates through the bloodstream as lipoproteins
• Free fatty acids make up a small percentage of total circulating lipids

Free Fatty Acids (FFAs)

• FFAs can diffuse easily across plasma membranes
• In the blood, they are generally bound to albumin (most abundant)

FFAs Sources

• Those not used in the synthesis of triglycerides that diffuse from intestinal epithelium
• Those that diffuse out of lipid reserves when triglycerides are broken down

Energy Source During Starvation

• It an important energy source during periods of starvation
• Is a great source of energy when glucose supplies are limited, especially in cells in the liver, cardiac muscle, skeletal muscle, etc.
• Cells are able to can metabolized

Lipoproteins

• Lipid–protein complexes
• Contain large insoluble glycerides and cholesterol
• There are four groups of lipoproteins:
  • Chylomicrons
  • Very low-density lipoproteins (VLDLs)
  • Low-density lipoproteins (LDLs): “bad cholesterol"
  • High-density lipoproteins (HDLs): “good cholesterol"

Chylomicrons

• Largest lipoproteins
• Are produced by intestinal epithelial cells from fats in food
• Carry absorbed lipids into lymph and then into the bloodstream

Protein Metabolism

• The body synthesizes 100,000-140,000 different proteins
• Each protein has different structures and functions
• All proteins are built from the same 20 amino acids
• Proteins function as enzymes, hormones, structural elements, and neurotransmitters
• Very little protein is used as an energy source

Amino Acid Catabolism

• In order for proteins to be used as an energy source the must be converted into substances that can enter citric acid cycle
• This conversion involves
  • Transamination
  • Deamination
  • Urea cycle
• Removal of an amino group requires a coenzyme derivative of vitamin B6

Transamination

• Attaches an amino group of amino acid to a keto acid
• Converts keto acid to an amino acid
• Leaves mitochondrion and enters cytosol -Available for protein synthesis

Deamination

• Prepares amino acid for breakdown in citric acid cycle
• Removes an amino group and hydrogen atom -Generates a toxic ammonium ion

Deamination (Function)

• Deamination generates ammonium ions primarily in liver cells
• Liver cells have enzymes that remove the toxic ammonium ions by synthesizing urea
• Through the urea cycle
• Urea is a fairly harmless water-soluble compound excreted in urine

Waste Products

• The urea cycle takes two metabolic waste products, ammonium ions and carbon dioxide and produces urea, a relatively harmless that is excreted in the urine

Amino Acids and ATP

• When glucose and lipid reserves are inadequate, liver cells:
  • Break down internal proteins
  • Absorb additional amino acids from the blood
• Amino acids are then deaminated
  • Carbon chains are sent to the mitochondria
• Not all amino acids enter the cycle at the same point
  • ATP benefits then vary

Catabolism Impractical

• The factor that make catabolism impractical is that: -Proteins are more difficult to break apart than complex carbohydrates or lipids
  • One by-product (ammonium ions) is toxic to cells -Proteins form the most important structural and functional components cells

Protein Synthesis

• The body synthesizes half of the amino acids needed to buld all proteins
• There are ten essential: -Eight are not synthesized at all -And two are insufficiently synthsized
• Non Essential Amino acids are made by the body on demand
• This requires amination which is the addition of an amino group

Nutrient Requirements of Tissues

• Nutrient requirements of tissues vary with the types and quantities of enzymes present in cells

Five Metabolic Tissues

• Liver
• Adipose tissue
• Skeletal muscle
• Nervous tissue
• Other peripheral tissues

Liver Role

• Focal point of metabolic regulation and control
• Great diversity of enzymes that break down or synthesize carbohydrates, lipids, and amino acids
• Hepatocytes, which:
  • Have an extensive blood supply
  • Monitor and adjust the nutrient composition of circulating blood
• All this translates to: Significant energy reserves (glycogen deposits)

Adipose Tissue Role

• Stores lipids, primarily as triglycerides
• Adipocytes are located in:
  • Areola tissue
  • the Mesenteries
  • Red and yellow bone marrows
  • Epicardium
  • Around eyes and kidneys

Skeletal Muscle Role

• Maintains substantial glycogen reserves
  • If other nutrients are unavailable
• Contractile proteins can be broken down
• Amino acids can be used as an energy source

Nervous Tissue

• It does not maintain reserves of carbohydrates, lipids, or proteins, so, it requires a reliable supply of glucose
  • Cannot metabolize other molecules
  • In the CNS, cannot function in low-glucose conditions
    • Individual becomes unconscious

Peripheral Tissue

• These do not maintain large metabolic reserves
• Can metabolize glucose, fatty acids, and other substrates
• Preferred energy source varies -According to instructions from the endocrine system

Absorptive and Postabsorptive

• Two patterns of daily metabolic activity
  • Absorptive state -Period following a meal when nutrient absorption is under way -Lasts about four hours -Postabsorptive state -Normal blood glucose levels are maintained -Body relies on internal energy reserves -Most cells break down lipids or amino acids
• Preserving glucose for use by nervous tissue

Lipid and Amino Acids

• Generate acetyl-CoA -Increased concentration of acetyl-CoA
• Causes ketone bodies to form
• A ketone body is an organic compound produced by fatty acid metabolism:
• Dissociates in solution, releasing a hydrogen ion

Ketone Bodies

• Three typea

  • Acetone
  • Acetoacetate
  • Betahydroxybutyrate

• The liver cannot metabolize the ketone bodies

• Peripheral cells absorb them from blood and reconvert them to acetyl-CoA for the citric acid cycle

• Fasting produces ketosis, the high concentration of ketone bodies that are in the body fluids

Ketonemia

• Appearance of ketone bodies in the bloodstream
• Lowers the blood's pH, thus the buffer body controls must be maintained
• Prolonged starvation leads to ketoacidosis
• Dangerous acidification of the blood caused by ketone bodies,which causes coma, cardiac arrhythmias, and death

Nutrition

• In order to maintain homeostasis indefinitely, the digestive track must absorb fluids, organic nutrients, minerals and vitamines
• This describes nutrition which is the absorption of nutrients from food, but the body's requirement for each nutrient varies
• Having a balance diet then is one of the most important aspects of maintain homeostasis

Nutrition

• Balanced diet should Contain all ingredients needed for homeostasis, if not malnutrition results which is an unhealthy state resulting from nutrient imbalance

Complete Proteins

• Proteins that provide all essential amino acids in sufficient quantities -Found in beef, fish, poultry, eggs, and milk
• Incomplete proteins are deficient is one or more essential amino acid -Found in plants

Minerals

• Are inorganic ions released through dissociation of electrolytes
• They are important due to: -Ions such as sodium and chloride determine this osmotic concentrations of the body fluids -Ions play major roles in physiological processes -Ions are essential cofactors and many enzymatic reactions

Types of Minerals

• The types of bulk minerals include: Sodium, potassium, chloride, calcium, phosphorus, and magnesium
• The types of trace minerals Iron, zinc, copper, manganese, cobalt, selenium, and chromium
• The body contains reserves of several important mineral

Vitamins

• Essential organic nutrients that function as coenzymes in vital enzymatic reactions -Two gropus ased on chemical structure and ccharacteristics
• *Fat-solube vitamines
• *Water soluble vitamines

Fat vs Water

• Fat soluble vitamines consist of : -Vitamine A -Vitamine D -Vitamine EL -and Vitamine K

• These vitamines must be absorbed primarily from the digestive tract aong with lipds of micelles

• And Skin synthesizes small amounts of vitamin D when exposed to sunlight

• Intestinal bacteria produce some vitamin K

Vitamine Types

• Vitamine A is required of:
• Maintains epithelia
• Required for synthesis of visual pigments- Vitamine D is Required for normal bone growth
• Vitamin E: Prevents breakdown of vitamin A and fatty acids
• Vitamin K is Essential for synthesis of clotting factors

Vitamine Reserve

• Body contains significant reserves of fat soluble vitamines due to:normal metabolism can continue several months without dietary sources, how ever :
• Hyovitaminosis or in other word vitamine deficiencies are some times rare in fat soluble vitamines as a result Hypervitaminosis is also possible
• Hypervitaminosis then is when dietary intake exceed body;s abilaty to use store or excrete a particular vitamine where ass:

Water Soluble V

• are componeants of coenzimes
• readily exchanged betwen fluid inigestive tract and circuating bloods
• readily excreted in urine

Bacteria

• The bacteria in our iintenstines produce: Five of the 9 water soluble vitamines and are capable of prodecung fat-soluable vitamine K
• Intestianal epathiliem easly adorb water soluble vitamines exce pt B12
• *B12 has a large molecules and it is required to bind to internsic factot before absorbsion

Metabolic Rate

• it is Average caloric expenditure
• Daily energy expenditures vary widely with activity
• Energy gains and losses
• Energy is released when chemical bonds are broken
• Energy is used to synthesize ATP in cells =Some energy is lost as heat

Mecanics of Measuring Enery

• Measuring energy:

• Energy required to raise the temperature of 1g of water by one degre to create 1 deg Celsius calorie (cal)

• Enerfy to heat 1 deg of H2O to one deg C, we must add 1 callorie

     =Energy required to raise the temperature of one kg of water to deg C, one must add a calorioe (Cal with a capotal *C) to a kallocal orkcal
  

Mechanics

• Energy content of food is an exercise in:
• Calonietry =Measures total energy released when bonds of organic molecules are broken
• Determined by burning food with oxygen and water in a calorimeter to burn the food

Rates

• Lipids release 9.46 kcal over grams.
• Carbohydrates release 4.18 kcal over grams
• Proteins release 4,32 kcal per gram
• Clinicians examine your metabolic state to determine calories used -Results can be expresseds as calories per hour, calories per day, OR cal per unit
• Body weight ber da
• Affected by exercise, age, sex, hormones, and climate to determine:

Metobolic Rate

• Basic meabolic rate
• the rate at which body expands energy while at rest to maintain vital functions -minimum resyung energy expenditure
  • measuring BMR involes moniteroing respiratory activity
• enery use is propprtiosnto ixyegn consumptiom in resting indivudials

Energy Ijtaje

• Regulation of entergy intake:
• throoxin controls ovrtall metabloismn
• Cholecystokinin (CCK) and adrenocorticotropic hormone (ACTH) suppress appetite
• Leptin is released by adipose tissue sueding abosrptive state to regulate:
• Blinds to CNS, newrons to suppress appetite -Ghtelin is released by empty stomach ti: Stimulates appetite

• Obsesity defined as = Body weight mor than 20
• Percent above ideal weight
• An epidemic causes --Heart disease =Cancer =Diabetes