Chapter 25
Metabolism

Functions of food

source of energy

essential nutrients

stored for future use

Metabolism is all the chemical reactions of the body

some reactions produce the energy stored in ATP that other reactions consume

all molecules will eventually be broken down and recycled or excreted from the body

Catabolism and Anabolism

Catabolic reactions breakdown complex organic compounds

providing energy (exergonic)

glycolysis, Krebs cycle and electron transport

Anabolic reactions synthesize complex molecules from small molecules

requiring energy (endergonic)

Exchange of energy requires use of ATP (adenosine triphosphate) molecule.

ATP Molecule & Energy

Each cell has about 1 billion ATP molecules that last for less than one minute

Over half of the energy released from ATP is converted to heat

Energy Transfer

Energy is found in the bonds between atoms

Oxidation is a decrease in the energy content of a molecule

Reduction is the increase in the energy content of a molecule

Oxidation-reduction reactions are always coupled within the body

whenever a substance is oxidized, another is almost simultaneously reduced.

Mechanisms of ATP Generation

Phosphorylation is

bond attaching 3rd phosphate group contains stored energy

Mechanisms of phosphorylation

within animals

substrate-level phosphorylation in cytosol

oxidative phosphorylation in mitochondria

in chlorophyll-containing plants or bacteria

photophosphorylation.

Phosphorylation in Animal Cells

In cytoplasm (1)

In mitochondria (2, 3 & 4)

Carbohydrate Metabolism--In Review

In GI tract

polysaccharides broken down into simple sugars

absorption of simple sugars (glucose, fructose & galactose)

In liver

fructose & galactose transformed into glucose

storage of glycogen (also in muscle)

In body cells --functions of glucose

oxidized to produce energy

conversion into something else

storage energy as triglyceride in fat

Fate of Glucose

ATP production during cell respiration

uses glucose preferentially

Converted to one of several amino acids in many different cells throughout the body

Glycogenesis

hundreds of glucose molecules combined to form glycogen for storage in liver & skeletal muscles

Lipogenesis (triglyceride synthesis)

converted to glycerol & fatty acids within liver & sent to fat cells

Glucose Movement into Cells

In GI tract and kidney tubules, Na+/glucose symporters

Most other cells, GluT facilitated diffusion transporters move glucose into cells

insulin increases number of GluT transporters in the membrane of most cells

in liver & brain, always lots of GluT transporters

Glucose 6-phosphate forms immediately inside cell (requires ATP) thus, glucose hidden in cell

Concentration gradient favorable for more glucose to enter

Glucose Catabolism

Cellular respiration

4 steps are involved

glucose + O2 produces
H2O + energy + CO2

Anaerobic respiration

called glycolysis (1)

formation of acetyl CoA (2)
is transitional step to Krebs cycle

Aerobic respiration

Krebs cycle (3) and electron transport chain (4)

Glycolysis of Glucose & Fate of Pyruvic Acid

Breakdown of six-carbon glucose molecule into 2 three-carbon molecules of pyruvic acid

10 step process occurring in cell cytosol

produces 4 molecules of ATP after input of 2 ATP

utilizes 2 NAD+ molecules as hydrogen acceptors

If O2 shortage in a cell

pyruvic acid is reduced to lactic acid so that NAD+ will be still available for further glycolysis

rapidly diffuses out of cell to blood

liver cells remove it from blood & convert it back to pyruvic acid

Formation of Acetyl Coenzyme A

Pyruvic acid enters the mitochondria with help of transporter protein

Decarboxylation

pyruvate dehydrogenase converts 3 carbon pyruvic acid to 2 carbon fragment (CO2 produced)

pyruvic acid was oxidized so that NAD+ becomes NADH

2 carbon fragment (acetyl group) is attached to Coenzyme A to form Acetyl coenzyme A which enter Krebs cycle

coenzyme A is derived from pantothenic acid (B vitamin).

Krebs Cycle (Citric Acid Cycle)

Series of oxidation-reduction & decarboxylation reactions occurring in matrix of mitochondria

It finishes the same as it starts (4C)

acetyl CoA (2C) enters at top & combines with a 4C compound

2 decarboxylation reactions peel 2 carbons off again when CO2 is formed

Krebs Cycle

Energy stored in bonds is released step by step to form several reduced coenzymes (NADH & FADH2) that store the energy

In summary: each Acetyl CoA
molecule that enters the Krebs
cycle produces

2 molecules of C02

one reason O2 is needed

3 molecules of NADH + H+

one molecule of ATP

one molecule of FADH₂

Remember, each glucose
produced 2 acetyl CoA molecules

The Electron Transport Chain

Series of integral membrane proteins in the inner mitochondrial membrane capable of oxidation/reduction

Each electron carrier is reduced as it picks up electrons and is oxidized as it gives up electrons

Small amounts of energy released in small steps

Energy used to form ATP by chemiosmosis

Chemiosmosis

Small amounts of energy released as substances are passed along inner membrane

Energy used to pump H+ ions from matrix into space between inner & outer membrane

High concentration of H+ is maintained outside of inner membrane

ATP synthesis occurs as H+ diffuses through a special H+ channel in inner membrane

Steps in Electron Transport

Carriers of electron transport chain are clustered into 3 complexes that each act as proton pump (expel H+)

Mobile shuttles pass electrons between complexes

Last complex passes its electrons (2H+) to a half of O2 molecule to form a water molecule (H2O)

Proton Motive Force & Chemiosmosis

Buildup of H+ outside the inner membrane creates + charge

electrochemical gradient potential energy is called proton motive force

ATP synthase enzyme within H+ channel uses proton motive force to synthesize ATP from ADP and P

Summary of Cellular Respiration

Glucose + O2 is broken down into CO2 + H2O + energy used to form 36 to 38 ATPs

2 ATP are formed during glycolysis

2 ATP are formed by phosphorylation during Krebs cycle

electron transfers in transport chain generate 32 or 34 ATPs from one glucose molecule

Summary in Table 25.1

Points to remember

ATP must be transported out of mitochondria in exchange for ADP

uses up some of proton motive force

Oxygen is required or many of these steps can not occur

Carbohydrate Loading

Long-term athletic events (marathons) can exhaust glycogen stored in liver and skeletal muscles

Eating large amounts of complex carbohydrates (pasta & potatoes) for 3 days before a marathon maximizes glycogen available for ATP production

Useful for athletic events lasting for more than an hour

Glycogenesis & Glycogenolysis

Glycogenesis

glucose storage as glycogen

4 steps to glycogen
formation in liver or
skeletal muscle

stimulated by insulin

Glycogenolysis

glucose release not a simple
reversal of steps

enzyme phosphorylase splits off a glucose molecule by phosphorylation to form glucose 1-phosphate

enzyme only in hepatocytes so muscle can’t release glucose

enzyme activated by glucagon (pancreas) & epinephrine (adrenal)

Gluconeogenesis

Liver glycogen runs low if fasting, starving or not eating carbohydrates forcing formation from other substances

lactic acid, glycerol & certain amino acids (60% of available)

Stimulated by cortisol (adrenal) & glucagon (pancreas)

cortisol stimulates breakdown of proteins freeing amino acids

thyroid mobilizes triglycerides from adipose tissue

Transport of Lipids by Lipoproteins

Most lipids are nonpolar and must be combined with protein to be tranported in blood

Lipoproteins are spheres containing hundreds of molecules

outer shell polar proteins
(apoproteins) & phospholipids

inner core of triglyceride &
cholesterol esters

Lipoprotein categorized by
function & density

4 major classes of lipoproteins

chylomicrons, very low-density, low-density & high-density lipoproteins

Classes of Lipoproteins

Chylomicrons (2 % protein)

form in intestinal epithelial cells to transport dietary fat

apo C-2 activates enzyme that releases the fatty acids from the chylomicron for absorption by adipose & muscle cells

liver processes what is left

VLDLs (10% protein)

transport triglycerides formed in liver to fat cells

LDLs (25% protein) --- “bad cholesterol”

carry 75% of blood cholesterol to body cells

apo B100 is docking protein for receptor-mediated endocytosis of the LDL into a body cell

if cells have insufficient receptors, remains in blood and more likely to deposit cholesterol in artery walls (plaque)

HDLs (40% protein) --- “good cholesterol”

carry cholesterol from cells to liver for elimination

Blood Cholesterol

Sources of cholesterol in the body

food (eggs, dairy, organ meats, meat)

synthesized by the liver

All fatty foods still raise blood cholesterol

liver uses them to create cholesterol

stimulate reuptake of cholesterol containing bile normally lost in the feces

Desirable readings for adults

total cholesterol under 200 mg/dL; triglycerides 10-190 mg/dL

LDL under 130 mg/dL; HDL over 40 mg/dL

cholesterol/HDL ratio above 4 is undesirable risk

Raising HDL & lowering cholesterol can be accomplished by exercise, diet & drugs

Fate of Lipids

Oxidized to produce ATP

Excess stored in adipose tissue or liver

Synthesize structural or important molecules

phospholipids of plasma membranes

lipoproteins that transport cholesterol

thromboplastin for blood clotting

myelin sheaths to speed up nerve conduction

cholesterol used to synthesize bile salts and steroid hormones.

Lipid Anabolism: Lipogenesis

Synthesis of lipids by liver cells = lipogenesis

from amino acids

converted to acetyl CoA & then to triglycerides

from glucose

from glyceraldehyde 3-phosphate to triglycerides

Stimulated by insulin when eat excess calories

Ketosis

Blood ketone levels are usually very low

many tissues use ketone for ATP production

Fasting, starving or high fat meal with few carbohydrates results in excessive beta oxidation & ketone production

acidosis (ketoacidosis) is abnormally low blood pH

sweet smell of ketone body acetone on breath

occurs in diabetic since triglycerides are used for ATP production instead of glucose & insulin inhibits lipolysis

Fate of Proteins

Proteins are broken down into amino acids

transported to the liver

Usage

oxidized to produce ATP

used to synthesize new proteins

enzymes, hemoglobin, antibodies, hormones, fibrinogen, actin, myosin, collagen, elastin & keratin

excess converted into glucose or triglycerides

no storage is possible

Absorption into body cells is stimulated by insulinlike growth factors (IGFs) & insulin

Protein Catabolism

Breakdown of protein into amino acids

Liver cells convert amino acids into substances that can enter the Krebs cycle

deamination removes the amino group (NH2)

converts it to ammonia (NH3) & then urea

urea excreted in the urine

Converted substances enter the Krebs cycle to produce ATP

Protein Anabolism

Production of new proteins by formation of peptide bonds between amino acids

10 essential amino acids are ones we must eat because we can not synthesize them

nonessential amino acids can be synthesized by transamination (transfer of an amino group to a substance to create an amino acid)

Occurs on ribosomes in almost every cell

Stimulated by insulinlike growth factor, thyroid hormone, insulin, estrogen & testosterone

Large amounts of protein in the diet do not cause the growth of muscle, only weight-bearing exercise

Phenylketonuria (PKU)

Genetic error of protein metabolism that produces elevated blood levels of amino acid phenylalanine

causes vomiting, seizures & mental retardation

normally converted by an enzyme into tyrosine which can enter the krebs cycle

Screening of newborns prevents retardation

spend their life with a diet restricting phenylalanine

restrict Nutrasweet which contains phenylalanine

Metabolic Adaptations

Absorptive state

nutrients entering the bloodstream

glucose readily available for ATP production

4 hours for absorption of each meal so absorptive state lasts for 12 hours/day

Postabsorptive state

absorption of nutrients from GI tract is complete

body must meet its needs without outside nutrients

late morning, late afternoon & most of the evening

assuming no snacks, lasts about 12 hours/day

more cells use ketone bodies for ATP production

maintaining a steady blood glucose level is critical

Metabolism During Fasting & Starvation

Fasting means going without food for hours/days

Starvation means weeks or months

can survive 2 months or more if drink enough water

amount of adipose tissue is determining factor

Nutritional needs

nervous tissue & RBC need glucose so amino acids will be broken down for gluconeogenesis

blood glucose stabilizes at 65 mg/100 mL

lipolysis releases glycerol used in gluconeogenesis

increase in formation of ketone bodies by liver cells due to catabolism of fatty acids

by 40 days, ketones supply 2/3’s of brains fuel for ATP

Absorption of Alcohol

Absorption begins in the stomach but is absorbed more quickly in the small intestine

fat rich foods keep the alcohol from leaving the stomach and prevent a rapid rise in blood alcohol

a gastric mucosa enzyme breaks down some of the alcohol to acetaldehyde

Females develop higher blood alcohols

have a smaller blood volume

have less gastric alcohol dehydrogenase activity

Metabolic Rate

Rate at which metabolic reactions use energy

energy used to produce heat or ATP

Basal Metabolic Rate (BMR)

measurements made under specific conditions

quiet, resting and fasting condition

Basal Temperature maintained at 98.6 degrees

shell temperature is usually 1 to 6 degrees lower

Heat Production

Factors that affect metabolic rate and thus the production of body heat

exercise increases metabolic rate as much as 15 times

hormones regulate basal metabolic rate

thyroid, insulin, growth hormone & testosterone increase BMR

sympathetic nervous system’s release of epinephrine & norepinephrine increases BMR

higher body temperature raises BMR

ingestion of food raises BMR 10-20%

children’s BMR is double that of an elderly person

Mechanisms of Heat Transfer

Temperature homeostasis requires mechanisms of transferring heat from the body to the environment

conduction is heat exchange requiring direct contact with an object

convection is heat transfer by movement of gas or liquid over body

radiation is transfer of heat in form of infrared rays from body

evaporation is heat loss due to conversion of liquid to a vapor (insensible water loss)

Hypothalamic Thermostat

Preoptic area in anterior hypothalamus

receives impulses from thermoreceptors

generates impulses at a higher frequency when blood temperature increases

impulses propagate to other parts of hypothalamus

heat-losing center

heat-promoting center

Set in motion responses that either lower or raise body temperature

Thermoregulation

Declining body temperature

thermoreceptors signal hypothalamus to produce TRH

TRH causes anterior pituitary to produce TSH resulting in

vasoconstriction in skin

adrenal medulla stimulates cell metabolic rate

shivering

release of more thyroid hormone raises BMR

Increases in body temperature

sweating & vasodilation

Hypothermia

Lowering of core body temperature to 35°C (95°F)

Causes

immersion in icy water (cold stress)

metabolic diseases (hypoglycemia, adrenal insufficiency or hypothyroidism)

drugs (alcohol, antidepressants, or sedatives)

burns and malnutrition

Symptoms that occur as body temperature drops

shivering, confusion, vasoconstriction, muscle rigidity, bradycardia, acidosis, hypoventilation, coma & death

Regulation of Food Intake

Hypothalamus regulates food intake

feeding (hunger) center

satiety center

Stimuli that decrease appetite

glucagon, cholecystokinin, epinephrine, glucose & leptin

stretching of the stomach and duodenum

Signals that increase appetite

growth releasing hormone, opioids, glucocorticoids, insulin, progesterone & somatostatin

Guidelines for Healthy Eating

Nutrients include water, carbohydrates, lipids, proteins, vitamins and minerals

Caloric intake

women 1600 Calories/day is needed

active women and most men 2200 Calories

teenage boys and active men 2800 calories

Food guide pyramid developed by U.S. Department of Agriculture

indicates number of servings of each food group to eat each day

Food Guide Pyramid

Minerals

Inorganic substances = 4% body weight

Functions

calcium & phosphorus form part of the matrix of bone

help regulate enzymatic reactions

calcium, iron, magnesium & manganese

magnesium is catalyst for conversion of ADP to ATP

form buffer systems

regulate osmosis of water

generation of nerve impulses

Vitamins

Organic nutrients needed in very small amounts

serve as coenzymes

Most cannot be synthesized by the body

Fat-soluble vitamins

absorbed with dietary fats by the small intestine

stored in liver and include vitamins A, D, E, and K

Water-soluble vitamins are absorbed along with water in the Gl tract

body does not store---excess excreted in urine

includes the B vitamins and vitamin C

Antioxidant Vitamins

C, E and beta-carotene (a provitamin)

Inactivate oxygen free radicals

highly reactive particles that carry an unpaired electron

damage cell membranes, DNA, and contribute to atherosclerotic plaques

arise naturally or from environmental hazards such as tobacco or radiation

Protect against cancer, aging, cataract formation, and atherosclerotic plaque

Vitamin and Mineral Supplements

Eat a balanced diet rather than taking supplements

Exceptions

iron for women with heavy menstrual bleeding

iron & calcium for pregnant or nursing women

folic acid if trying to become pregnant

reduce risk of fetal neural tube defects

calcium for all adults

B12 for strict vegetarians

antioxidants C and E recommended by some

Fever

Abnormally high body temperature

toxins from bacterial or viral infection = pyrogens

heart attacks or tumors

tissue destruction by x-rays, surgery, or trauma

reactions to vaccines

Beneficial in fighting infection & increasing rate of tissue repair during the course of a disease

Complications-- dehydration, acidosis, & brain damage.

Obesity

Body weight more than 20% above desirable standard

Risk factor in many diseases

cardiovascular disease, hypertension, pulmonary disease,

non-insulin dependent diabetes mellitus

arthritis, certain cancers (breast, uterus, and colon),

varicose veins, and gallbladder disease.