Nutrition, Metabolism and Thermoregulation

Metabolism of Energy

containing Nutrients

Nutrition

• We eat, we digest, we absorb, then what?

• 3 fates for food = nutrients

1) Most are used to supply energy for life

2) Some are used to synthesize structural or functional molecules

3) The rest are stored for future use – love handles!

Nutrition

Figure 24.1

Nutrition: The Recommendation

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Nutrition for College StudentsFour

Groups:

Grease

Salt

Sugar

Alcohol

Protein Nutrition

Essential amino acids are the 9 (out of ~20) that we cannot synthesize in the liver by transamination; they must be present in our diet. All amino acids can be broken down for ATP energy production.

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Nutrition

• Summary of Carbohydrate, Lipid and Protein Nutrients (Table 24.1, p945)

• Vitamins (Table 24.2, p948-941)– Function as coenzymes– Not made in body (xcept D by skin, some B&K by

intestinal bacteria)– B vitamins

• Minerals (Table 24.3, p952-955)– 4% body weight– Ionized in body fluids/bound to organic

compounds (phospholipids, hemoglobin, Na+Cl-)

Metabolism• All biochemical reactions in the body• Balance between synthesis (anabolic) and breakdown (catabolic) reactions

– Anabolism • chemical reactions that combine simple, smaller molecules into more complex molecules • uses energy• protein formation from amino acids• carbohydrate formation from simple sugars

– Catabolism• chemical reactions that break down complex organic molecules into simpler ones• releases energy• proteins are broken down by various proteases

Metabolism (cont)• Relationship of catabolism to anabolism

Metabolism (cont)• Link between anabolism and

catabolism is ATP

– ATP energy is the “currency” used in most cellular energy exchanges

– Catabolic reactions provide the ATP energy that most anabolic reactions require

– Only about 10-30% of the energy released by catabolic reactions can be used• most chemical energy is lost as

“waste heat”• “waste heat” is not wasted; it

is essential in maintaining a constant body temperature

Metabolism (cont)• ATP– Allows for transfer of small but useful amounts of

energy from one molecule to another

– Cell's entire amount of ATP is recycled approximately every minute

– ATP is NOT for long term energy storage• too reactive in the cell• other molecules available for energy storage (neutral fats,

glycogen, creatine phosphate, etc.)

– About 8kg (17 lb) of ATP is produced every hour in an average male

– Total amount of ATP present in the body at any time is only about 50g (0.050 kg)

Metabolism (cont)• ATP (cont)

– Energy is released by breaking the third phosphate group’s bond

– ATP ADP + Pi

• a reversible reaction• the energy released is enough

to drive anabolic reactions

– ATP ADP + CrP • creatine provides energy

storage in skeletal muscle• allows for more ATP to be

formed when O2 is less readily available during skeletal muscle contraction

ATP is composed of 3 things:

• The sugar ribose• The base adenine• 3 phosphate groups These phosphates are the key to the activity of ATP.

• Energy is stored by adding a phosphate to ADP

• ADP + Pi ATP• Energy stored

(endogonic / endo thermic rxn)

• Energy is released by breaking a phosphate off ATP

• ATPADP + Pi• Energy released

(Exogonic/exothermic rxn)

Energy Production• Energy is stored in chemical bonds• Oxidation-Reduction (Redox) reactions:

– Oxidation component:• also known as dehydrogenation reactions• remove electrons from molecules

– decreases the energy remaining in the oxidized molecule

– generally, 2e- (and 2H+) are removed simultaneously• Can also be the gain of oxygen

Energy Production (cont.)

•Reduction component:–addition of

electrons to a molecule– increases the

energy of the reduced molecule

•These 2 component reactions are always coupled: oxidation-reduction reactions

Oxidation Is Losing Electrons, Reduction Is Gaining Electrons: OIL RIG

Electron Loss Means Oxidation: ELMO Losing Electrons Oxidation, Gaining Electrons Reduction: LEO the lion. GER! or LEO

says GER

Energy Production (cont.)• ATP Generation

– Addition of phosphate to a chemical compound is phosphorylation

– 3 mechanisms for this:1. Substrate level

phosphorylation – a high-energy phosphate group is transferred directly from a molecule to ADP to make ATP

For example, when the energy stored on a high-energy phosphate group on creatine phosphate is transferred to ADP to make ATP in skeletal muscles

CK transfers a high energy phosphate from creatine phosphate to ADP

Energy Production (cont.)ATP Generation

2. Oxidative phosphorylation

• electrons (H+) removed from molecules

• enzymes combine H+ with O2, releasing enough energy for ATP formation

3. Photo-phosphorylation

• photosynthesis

Carbohydrate Metabolism• General – 80% of carbohydrates ingested contain

glucose; remainder: fructose, galactose– glucose is the body's preferred

carbohydrate energy source

• Fate of carbohydrates -- depends on needs of body cells– ATP production– Amino acid synthesis– Glycogenesis – Lipogenesis – Excretion in urine (minimal)

Carbohydrate Metabolism (cont.)

• Glucose anabolism– Glucose storage:

glycogenesis• glycogen formation is

stimulated by insulin

• glucose not needed immediately is stored in the liver (25%) and in skeletal muscle (75%)

– Glucose release: glycogenolysis• converts glycogen to

glucose

• occurs between meals, stimulated by glucagon and epinephrine

Carbohydrate Metabolism (cont.)

• Glucose anabolism (cont.)– Formation of glucose from proteins & fats:

gluconeogenesis • When blood glucose level is low, you eat; if

glucose remains low, body catabolizes some proteins and fats• Stimulated by cortisol and thyroid hormone– cortisol (glucocorticoids) mobilizes proteins,

making AA's available– thyroid hormone mobilizes proteins (AA's) and

may mobilize lipids• Epinephrine, glucagon, hGH also stimulate• These five hormones are often referred to as the

“insulin antagonists.”

Glucose Catabolism• Glucose oxidation is known as cellular

respiration

– Complete catabolism of each molecule of glucose to CO2, H2O

–Maximum yield of 38 ATP molecules/glucose• 38% of the energy present in a glucose• excellent efficiency for a biological system• the rest of the energy is “waste heat”

– 2 linked enzymatic pathways are involved in glucose catabolism • glycolysis• Kreb’s cycle

• Cells make ATP in an organelle called the mitochondria

In eukaryotes, respiration occurs in 3 steps

1. Glyco lysis (sugar breaking)

2. Kreb’s Cycle (Citric Acid Cycle)3. Electron Transport Chain

• Glycolysis occurs in the cytosol of the cell and makes 2 ATP.

• Glycolysis starts with the monosacchride (sugar) glucose

• And uses the coenzyme NAD+

• The Kreb’s cycle or (Citric Acid Cycle) occurs in the matrix of the mitochondria and makes 2ATP

• The electron transport chain occurs across the inner membrane of the mitochondria.

• It makes 34 ATP and requires oxygen

• It only occurs in eukaryotes

• Sometimes, under an aerobic (lack of oxygen) conditions, like strenuous exercise, eukaryotes undergo fermentation

• This is called lactic acid fermentation.

• Fermentation does NOT make energy

• It changes the coenzyme NADH+H+ back to NAD+ for use in glycolysis

• Prokaryotes do not have mitochondria or ANY membrane bound organelle.

• They carry out respiration in the cytosol

• Prokaryotes use the fermentation process to change the coenzyme NADH+H+ back to NAD+

• Microorganism fermentation produces ethyl alcohol and CO2

Glucose Catabolism Overview

C6H12O6 6CO2(waste) + 12H2O + 36-38ATP(useful

energy)

Summary:Carbohydrate Metabolic Reactions

LipidsBeta oxidation breaks down fatty acids to form acetyl Coenzyme A.

Lipids are more reduced (have fewer oxygens); therefore, they have more potential chemical energy and can be more fully oxidized as an energy fuel.

Therefore, we gain more energy, gram for gram, from fats than from carbohydrates.

Lipogenesis and Lipolysis

Figure 24.14

• The liver: – Synthesizes lipoproteins for transport of

cholesterol and fats–Makes tissue factor, a clotting factor– Synthesizes cholesterol for acetyl CoA– Uses cholesterol to form bile salts

• Certain endocrine organs (ovaries, testes, and adrenal cortex) use cholesterol to synthesize steroid hormones

Lipid Metabolism: Synthesis of Structural Materials

Protein Metabolism

Amino acids may be deaminated and the resulting “carbon skeletons” of whatever composition, can be entered into the glycolytic or Krebs cycle pathways to yield an energy harvest of ATPS. The amino groups will be joined with CO2 molecules to form the nitrogenous waste urea.

Summary:Lipid and Protein Metabolic Reactions

Liver Metabolism

• Hepatocytes carry out over 500 intricate metabolic functions

• A brief summary of liver functions– Packages fatty acids to be stored and

transported– Synthesizes plasma proteins– Forms nonessential amino acids– Converts ammonia from deamination

to urea– Stores glucose as glycogen, and

regulates blood glucose homeostasis– Stores vitamins, conserves iron,

degrades hormones, and detoxifies substances

Cholesterol

• Lipoproteins are classified as:– HDLs – high-density lipoproteins have

more protein content– LDLs – low-density lipoproteins have a

considerable cholesterol component– VLDLs – very low density lipoproteins

are mostly triglycerides

Cholesterol

Plasma Cholesterol Levels

• The liver produces cholesterol:– At a basal level of cholesterol regardless

of dietary intake– Via a negative feedback loop involving

serum cholesterol levels– In response to saturated fatty acids,

increase cholesterol production in liver

Non-Dietary Factors Affecting Cholesterol

• Stress, cigarette smoking, and coffee drinking increase LDL levels

• Aerobic exercise increases HDL levels

• Body shape is correlated with cholesterol levels– Fat carried on the upper body is

correlated with high cholesterol levels – Fat carried on the hips and thighs is

correlated with lower levels

The Daily Metabolic Cycle• The body shifts back

and forth physiologically between the absorptive state and the postabsorptive state.

• The absorptive state occurs for approximately 4 hours after each regular meal.

• The postabsorptive state takes over until the next meal can be absorbed.

Regulation of Food Intake• Weight management– If energy consumption (food intake) equals

energy utilized (activity), then body weight will remain constant

– Activity and consumption levels vary day to day, but individuals keep relatively constant weight for long periods of time

–Many individuals in affluent nations have an imbalance between intake and use obesity

Regulation of Food Intake

• Hypothalamus - complex integrating center receiving sensory information from all parts of the body

• The arcuate nucleus contains several peptides that influence feeding

–Neuropeptide Y (NPY)/Agouti-related peptide (AgRP) stimulate feeding

–Pro-opiomelanocortin (POMC)/ cocaine- and amphetamine-regulated transcript (CART) inhibit feeding

Regulation of Food Intake (cont.)• The hypothalamus has several inputs

– Vagal inputs from the gut• Distenstion

– Nutrients• Blood glucose• Blood amino acids• Blood fatty acids

– Hormones• Insulin, CCK• Leptin – secreted by adipose cells• Glucagon, epinephrine• Ghrelin – secreted by stomach

– Temperature - high temp decreases appetite

– Social and psychological factors

Thermogenesis

Core and Shell Temperature• Organs in the core

(within the skull, thoracic, and abdominal cavities) have the highest temperature

• The shell, essentially the skin, has the lowest temperature

• Blood serves as the major agent of heat transfer between the core and shell

• Core temperature remains relatively constant, while shell temperature fluctuates substantially (20C–40C)

Mechanisms of Heat Exchange• The body uses four

mechanisms of heat exchange– Radiation – loss of heat in the

form of infrared rays– Conduction – transfer of heat

by direct contact– Convection – transfer of heat to

the surrounding air– Evaporation – heat loss due to

the evaporation of water from the lungs, mouth mucosa, and skin (insensible heat loss)

• Evaporative heat loss becomes sensible when body temperature rises and sweating produces increased water for vaporization

Countercurrent Heat Exchange

• The body uses four mechanisms of heat exchange– Radiation – loss of heat in the form

of infrared rays– Conduction – transfer of heat by

direct contact– Convection – transfer of heat to

the surrounding air– Evaporation – heat loss due to the

evaporation of water from the lungs, mouth mucosa, and skin (insensible heat loss)

• Evaporative heat loss becomes sensible when body temperature rises and sweating produces increased water for vaporization

Mechanisms of Heat Exchange

• The body uses four mechanisms of heat exchange– Radiation – loss of heat in the form

of infrared rays– Conduction – transfer of heat by

direct contact– Convection – transfer of heat to

the surrounding air– Evaporation – heat loss due to the

evaporation of water from the lungs, mouth mucosa, and skin (insensible heat loss)

• Evaporative heat loss becomes sensible when body temperature rises and sweating produces increased water for vaporization

Role of the Hypothalamus

• The main thermoregulation center is the preoptic region of the hypothalamus

• The heat-loss and heat-promoting centers comprise the thermoregulatory centers

• The hypothalamus:– Receives input from thermoreceptors in the

skin and core– Responds by initiating appropriate heat-loss

and heat-promoting activities

Mechanisms of Body Temperature Regulation

Hyperthermia

• Normal heat loss processes become ineffective and elevated body temperatures depress the hypothalamus

• This sets up a positive-feedback mechanism, sharply increasing body temperature and metabolic rate

• This condition, called heat stroke, can be fatal if not corrected

Heat Exhaustion

• Heat-associated collapse after vigorous exercise, evidenced by elevated body temperature, mental confusion, and fainting

• Due to dehydration and low blood pressure

• Heat-loss mechanisms are fully functional

• Can progress to heat stroke if the body is not cooled and rehydrated

Fever

• Controlled hyperthermia, often a result of infection, cancer, allergic reactions, or central nervous system injuries

• White blood cells, injured tissue cells, and macrophages release pyrogens that act on the hypothalamus, causing the release of prostaglandins

• Prostaglandins reset the hypothalamic thermostat

• The higher set point is maintained until the natural body defenses reverse the disease process

Response to Heat• Radiation away of infrared radiation

• Convection and conduction of heat to air or water surrounding the body

• Evaporation from sweating and from ventilating respiratory membranes

• Vasodilation of cutaneous capillary beds

• Decreased hormonal activity leading to decreased basal metabolic rate (BMR)

• Behavioral: stop exercising; move to the shade, take off clothes, turn on a/c, etc.

Response to Cold

• Increased hormone activity (thyroxine, epinephrine) leading to increased (BMR)

• Increased sympathetic ANS activity leading to increased (BMR)

• Shivering of skeletal muscles

• Vasoconstriction of dermal capillary beds

• Behavioral: start exercising, huddle together, use clothing and shelter, use fire or other means of heating the surroundings

Glucose Catabolism: Glycolysis• Occurs in cytosol

• 1 glucose 2 pyruvates (pyruvic acid)

• Net gain: 2 ATP’s– 2 ATP’s used– 4 ATP’s made

• Net gain 2 NADH + 2H+

(aerobic conditions)

Oxidative Phosphorylation• written by Greg Crowther and Do Peterson

• Do you see the athletes run? Do you see the children crawl?Every soul beneath the sun -- Ox phos fuels them one and all.

• You can't see inside their cells; If you could, here's what you'd see:Small cigar-shaped organelles Synthesizing ATP.

• Matrix protons get pumped out To the intermembrane space.Then they take an inward route Through the ATP synthase.

• [Preacher's message:]Fuel the muscles. Feel the sunshine.Feel the ATP. See the children.See the athletes. Ox phos fuels us you and me.In the morning, In the mid-day,In the afternoon. In the evening,In the late night, Ox phos fuels us me and you.When I feel up, When I feel good,When I'm movin' 'round, When I sit up,When I stand up, When I make my sound.All right, now.Oxidative phosphorylation. Oxidative phosphorylation.Oxidative phosphorylation. Oxidative phosphorylation....

Glucose, Glucose• written by Jeff Barry and Andy Kim; scientific lyrics by Greg Crowther

• Glucose -- ah, sugar sugar --You are my favorite fuel From the blood-borne substrate pool.Glucose -- monosaccharide sugar --You're sweeter than a woman's kiss

• 'Cause I need you for glycolysis.• I just can't believe the way my muscles take you in. (For you, they'll open the door.)

All it takes is a little bit of insulin (To upregulate GLUT4).• Ah, glucose -- ah, sugar sugar --You help me make ATP When my predators

are chasing me.Ah, glucose -- you're an aldehyde sugar,

• And you're sweeter than a woman's kiss'Cause I need you for glycolysis.

• I just can't believe the way my muscles break you down. (My glycogen is almost gone.)A few more seconds and I'll be rigor mortis-bound. (Acidosis done me wrong.)

• Your sweet is turning sour, baby.I'm losing all my power, baby. I'm gonna make your muscles ache.No, no, no!I'm swimming in lactate, baby. Yes, I'm swimming in lactate, baby.Now I'm drowning in lactate, baby. I'm gonna make your muscles ache.No, no, no!I'm drowning in lactate, baby.

• Ah, glucose -- ah, sugar sugar -- I used you up and you left me flat;Now I'll have to get my kicks from fat.Oh, glucose, glucose, sugar, sugar, The honeymoon is over now.

Glucose Catabolism• Fate of pyruvate - depends

on O2

– Without O2: NADH + H+ + pyruvate lactic acid

– With O2:• Pyruvate converted to acetyl

coenzyme A (acetyl CoA)• This reaction couples glycolysis

to the Krebs cycle

Glucose Catabolism• Pyruvic acid - formation of acetyl coenzyme A (Acetyl

CoA) + CO2 – lose one carbon from pyruvate to form CO2 (waste)

– the remaining two carbons, the acetyl group, join with CoA, to generate NADH + H+ (1 from each pyruvate = 2 NADH + 2H+ total from one glucose)

Glucose Catabolism: Krebs Cycle• Krebs cycle / Citric

Acid Cycle / Tricarboxylic Acid Cycle (TCA)– Oxidation of acetyl

Coenzyme A– Reduction of

coenzymes (NAD+, FAD+)

• Oxidative phosphorylation– Uses NADH2‘s and

FADH2‘s to make additional ATPs

Glucose Catabolism

Glycolysis and Krebs Cycle combined total:

6 CO2 (waste) + 6 H2O10 NADH2 + 2 FADH2 +4 ATP (energy harvest)

Electrons Source: NADH2/FADH2 from glycolysis and Krebs cycle

High‑energy electrons enter the system, and low‑energy electrons leave

Glucose Catabolism: Oxidative Phosphorylation

Electron Transport

• Oxidative phosphorylation – O2 is the final electron

acceptor for low‑energy electrons from last of the carrier molecules

– NADH2 3 ATP– FADH2 2 ATP

• Enzyme cytochrome oxidase splits apart O2 molecules– Combines each O atom

with 2 H+’s to make water

Animal Physiology, Hill et al., 2004

Resources• Thermoregulation, Temperature & Radiation• Metabolism, Energy Balance & Temperature Regulation