Chapter 25: Metabolism Primary sources for figures and content: Marieb, E. N. Human Anatomy &...

Chapter 25:

Metabolism

Primary sources for figures and content:

Marieb, E. N. Human Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.

Martini, F. H. Fundamentals of Anatomy & Physiology. 6th ed. San Francisco: Pearson Benjamin Cummings, 2004.

Metabolism

• Digestion + Absorption by GI monomers (building blocks) for ATP or biomolecule synthesis

• Metabolism = sum of all chemical reactions in the body

Metabolism

Figure 25–1

Metabolism1. Catabolism

– Breakdown of organic moleculesA.Hydrolysis

- Large molecules into monomersB.Cellular Respiration

- Oxidation of monomers in mitochondria- 40% of energy ATP- 60% of energy heat

2. Anabolism– Synthesis of new organic molecules for

• Cell maintenance and repair & Growth • Formation of secretions & Nutrient reserves

Nutrient Use in Cellular Metabolism

Figure 25–2 (Navigator)

Catabolism supplies ATP and monomers

to drive anabolism

Carbohydrate Metabolism


1. Carbohydrate Metabolism– Carbs are easiest to catabolize for

energy, always used first– Cellular respiration

•Oxidizes glucose + oxygen carbon dioxide + water and generates ATP

Cellular Respiration Review1. Glycolysis


Cellular Respiration Review1. Glycolysis

• Anaerobic, occurs in the cytoplasm• 1 glucose is oxidized into 2 pyruvic acids• 2 ATP produced by substrate level phosphorylation• 2 NADH produced by reduction of NAD via oxidation

of glucose• In no Oxygen available, pyruvic acid is reduced to

lactic acid (fermentation)– Erythrocytes (RBCs) glycolysis only (no mitochondria)– Skeletal muscle fermentation when no Oxygen– Neurons and cardiac muscle cannot ferment, need oxygen

Cellular Respiration Review2. Decarboxylation + Kreb/Citric Acid Cycle

Figure 25–4a (Navigator)

Figure 25–4b

Cellular Respiration

Review2.

Decarboxylation + Kreb/Citric Acid

Cycle

• Occur in matrix of mitochondria• Decarboxylation:

– 2 pyruvic acid decarboxylated and oxidized into 2 acetyl CoA + 2 CO2 + 2 NADH

• Citric Acid Cycle:– 2 acetyl combined with 2 oxaloacetic acids creating 2

citric acids– Citric acid decarboxylated and oxidized

4 CO2, 6 NADH, 2 FADH2

– 2 ATP generated by substrate level phosphorylation

Cellular Respiration Review2. Decarboxylation + Kreb/Citric Acid Cycle

Cellular Respiration Review 3. Electron Transport

Chain/Oxidative Phosphorylation

Figure 25–5a (Navigator)



Figure 25–5b



• Aerobic, occurs on cristae of mitochondria

• NADH and FADH2 reduced during glycolysis and citric acid cycle are oxidized

• Electrons are passed to cytochromes, finally accepted by oxygen

• 32 ATP generated by chemiosmosis/oxidative phosphorylation

• 12 H2O produced as waste from oxidation of oxygen

Summary: Complete Aerobic Cellular Respiration

Figure 25–6

With Oxygen1 glucose =36 ATP

Without Oxygen1 glucose = 2 ATP(0 ATP in neurons

and cardiac muscle, where fermentation

is not possible)


2. Carbohydrate Anabolism– All carbohydrates and lactic acid can be

converted to glucose– Gluconeogenesis

•Synthesis of glucose from a non-carbohydrate precursor

–e.g. glycerol, amino acids, lactic acid


3. Functions of Glucose– Stored as glycogen via Glycogenesis– Used to generate ATP– To create other carbohydrates

•Cell membrane receptors•Nucleic acids

Carbohydrate Breakdown

and Synthesis

Figure 25–7

Lipid Metabolism

Lipid Metabolism1. Lipid Catabolism

– Triglycerides are most common– Lipolysis

•Triglycerides glycerol + 3 fatty acidsA. Glycerol pyruvic acid

citric acid cycle generate 18 ATPB. Fatty Acids undergo β-oxidation to become 2

carbon acetyl citric acid cycle each 2-C fragment generates 17 ATP

– Carbon for carbon, lipids have 1.5x the energy of carbohydrates but are more difficult to use

Beta–Oxidation


Lipid Metabolism

1. Lipid Catabolism– Lipolysis is common to hepatocytes, cardiac

muscle, skeletal muscle for ATP synthesis– Not possible in neurons– Not water soluble, difficult for enzymes to

access– Lipolysis requires oxygen for ATP synthesis,

no fermentation

Lipid Metabolism

2. Lipid AnabolismA. Lipogenesis

•Triglycerides synthesized from cellular respiration intermediates

–Glycerol from glycolysis products–Fatty acids from Acetyl Co A

B. Cholesterol Synthesis•From any saturated fat molecule

C. Essential Fatty Acids

Lipid Metabolism

2. Lipid AnabolismC. Essential Fatty Acids

•Must be ingested in diet, no synthesis1. Linolenic acid = Omega 3 fatty acid2. Linoleic acid = Omega 6 fatty acid**Both used to synthesize arachidonic

acid, to synthesize eicosanoids (leukotrienes and protaglandins), for cell signaling

Lipid Metabolism3. Functions of Lipids

– Catabolism to generate ATP •Breakdown of triglycerides, mostly

– Cell membranes •phospholipids, glycolipids, cholesterol

– Myelin sheaths on axons– Bile salts– Steroid hormones– Cell signaling molecules– Energy reserve, 80% of total = triglycerides– Insulation and protection

Lipid Metabolism

4. Lipid Transport– Free fatty acids bound to albumins in blood– Others bound to proteins to form lipoproteins

•Soluble lipoproteins, bind specific receptors– Five classes of lipoproteins based on size and

composition•High protein content = High density•High lipid content = Low density

Lipoprotein Classes

• Increased lipids = decreased density1. Chylomicrons

– 95% triglycerides, from intestinal epithelium– Delivers lipids from gut to liver

2. Very Low Density Lipoproteins– Triglycerides (at high levels), phospholipids and

cholesterol– Delivers triglycerides from liver to tissues

3. Intermediate Density Lipoproteins– VLDLs with triglycerides removed– Return to liver for processing

Lipoprotein Classes

• Increased lipids = decreased density4. Low Density Lipoproteins

– High cholesterol, low triglycerides and phospholipids

– Deliver cholesterol from liver to tissues5. High Density Lipoproteins

– Equal protein and lipids (cholesterol and phospholipids

– Return cholesterols to liver for degradation

Lipoprotein Distribution1. Liver synthesizes VLDLs and releases them into blood2. Triglycerides are removed in capillaries making IDLs

from the VLDLs3. IDLs return to liver, triglycerides are removed and

proteins are altered, making LDLs from the IDLs which are released to blood

4. LDLs travel to peripheral tissues5. Cells endocytose LDLs and break them down6. Extra cholesterol diffuses out of the cells and enters

the blood

Lipoprotein Distribution

7. Cholesterol binds to HDLs in blood and returns to liver

8. HDLs at liver have cholesterol extracted to form

- empty HDLs, - new LDLs, - and bile salts

9. Empty HDLs return to the blood to pick up free cholesterol

Lipid Transport

and Utilization

Figure 25–9

Cholesterol and Health• Normal:

– HDLs > 60 mg/ml– LDLs < 160 mg/ml

• > 260 mg/ml LDLs need immediate medication or risk cardiovascular disease and heart attack

• Diet rich in saturated fats (animal) Triggers synthesis of cholesterol and blocks excretion/conversion by liver

• Diet rich in non-hydrogenated unsaturated fats (plants) enhance excretion and conversion to bile salts

Protein Metabolism

Proteins Metabolism

• Amino acids usually recycled to new proteins

• When carbs and lipids are lacking or amino acids are in excess, proteins can be catabolized for ATP or stored as fat

Protein Metabolism1. Amino Acid Catabolism• Deamination

– Amino group is removed, Requires vitamin B6• Generate ammonia = toxic

– Converted by liver to urea– Excreted in urine

• Carbon chain citric acid cycle for ATP• Different amino acids produce different amounts of ATP, some

are not used at all• Catabolism is difficult, inefficient and toxic• Last resort for energy!

Protein Metabolism1. Amino Acid Catabolism

Protein Metabolism

2. Amino Acid AnabolismA. Essential Amino Acids

– 8 for adults, 10 for children– Must be ingested, no synthesis

B. Synthesis– 12 can be synthesized using carbon backbone

from other amino acids– Amination = addition of amino group– We synthesize 500-1000 lbs of protein in our

lifetime

Protein Metabolism2. Amino Acid Anabolism

Figure 25–11

Phenylketonuria

• Lack of enzyme to convert phenylalanine to tyrosine

• Tyrosine is needed for melanin• Deaminated phenylalanine levels

rise neurotoxic affects

Protein Metabolism

3. Functions of Proteins– Cell structural components– Enzymes– hormones

Summary: Pathways of Catabolism and Anabolism

Figure 25–12

Nucleic Acid Metabolism

Nucleic Acid Metabolism• Nucleotides usually recycled for new nucleic acids• DNA never catabolized for energy• RNA only under extreme conditions• Nucleotide hydrolyzed to pentose sugar, nitrogenous base,

and phosphate– Sugar glycolysis for ATP– Pyrimidine bases (C, U) acetyl citric acid cycle for

ATP– Purine bases (A, G) deaminated

•excreted as uric acid•NOT USED FOR ATP

Gout

• Crystals of uric acid in joints• Causes pain and swelling

How would a diet that is deficient in pyridoxine (vitamin B6) affect protein

metabolism?

A. It would interfere with protein metabolism.

B. It would enhance protein metabolism.

C. It would cause the use of different coenzymes.

D. Pyridoxine is not involved in protein metabolism.

Elevated levels of uric acid in the blood can be an indicator of increased

metabolism of which organic compound?

A. nucleic acids

B. proteins

C. carbohydrates

D. lipids

Why are high-density lipoproteins (HDLs) considered beneficial?

A. They increase lipid metabolism.

B. They decrease blood pressure.

C. They increase blood pH.

D. They reduce fat and cholesterol in the bloodstream.

Metabolic Interactions:5 regions of metabolism

1. Liver– Site of metabolic regulation and control– Can break down or synthesize most molecules

for use by other cells– Stores glycogen reserves

2. Adipose– Stores triglyceride reserves

3. Skeletal Muscle– Stores glycogen reserves– Has contractile proteins that can be catabolized

Metabolic Interactions:5 regions of metabolism

4. Neural Tissue– High energy demand but no reserves – Requires constant supply of glucose

5. Peripheral Tissues– No reserves– Catabolize a wide range of substrates

Patterns of Metabolic Activity

1. The Absorptive State- Anabolism exceeds catabolism

2. The Post Absorptive State- Catabolism dominates

1. Absorptive State• Occurs for ~ 4 hr post meal while nutrients are being

transported to liver then tissues• Some nutrients are used immediately, some are stored as

reservesA. Hormones involved

1. Insulin: - promotes glucose uptake and utilization by cells

2. Growth hormone: - promotes amino acid uptake and protein synthesis by cells

3. Androgens and Estrogens : - promote amino acid utilization in protein synthesis

1. Absorptive State

B. Tissues involved1. Liver:

- Regulates blood glucose levels- Removes excess glucose from blood and performs

glycogenesis (formation of glycogen from glucose)- Excess glucose triglycerides VLDLs for storage

in adipocytes- Amino acids not tightly regulated

- Some absorbed for protein and enzyme synthesis- Some converted to more rare amino acids for use by

body cells

1. Absorptive State

B. Tissues involved2. Adipose Tissue:

- Absorb fatty acids and glycerol from the blood and triglycerides from VLDLs

- Absorb glucose for ATP synthesis to drive lipogenesis (triglyceride formation)

- All excess nutrients converted and stored as triglycerides

3. Peripheral Tissues:- Absorb glucose for ATP synthesis- Absorb amino acids for protein synthesis

2. Post Absorptive State

• Periods when there is no more absorption from GI

• Cells must rely on energy reserves– Glycogen: liver and skeletal muscle– Triglycerides: adipose tissue– Proteins: muscle tissue

• Primary goal is to maintain glucose levels to the brain

2. Post Absorptive StateA. Hormones involved

1. Glucagon- Promotes release of glucose from liver

2. Epinephrine- Promotes release of glucose from liver- Promotes lipolysis in adipose and release of glycerol

and fatty acids3. Glucocorticoids

- Inhibits use of glucose of body tissues- Promotes use of fatty acids

4. Growth Hormone: Complements glucocorticoids*Blood glucose decr. glucagon + epinephrine incr., insulin decr.

2. Post Absorptive StateB. Tissues involved

A. Liver- Glycogenolysis to cleave glucose from glycogen and

release it into blood- Gluconeogensis (via glucocorticoid stimulation) to

synthesize glucose from lipids- Triglyceride conversion

- Glycerol glucose- Fatty acids acetyl ketone bodies

- Amino acid conversion- Amino acids deaminated ketone bodies


B. Tissues involvedA. Liver

- Amino acid conversion- Ketone bodies released into blood, absorbed

by peripheral tissues converted to acetyl catabolized in Citric Acid Cycle

*During starvation• High concentrations of ketone bodies will be

present in body fluids = Ketosis

Ketosis1. During Starvation

– Oxaloacetic acid from Citric Acid Cycle will be converted into glucose for brain

– Acetyl and ketone bodies will not be able to enter citric acid cycle

– Ketone bodies (acids and acetone) build up– Can lead to ketoacidosis (low blood pH) death– Long term nonfetal ketosis bone loss, kidney damage,

heart disease2. Diabetes mellitus

– No insulin no glucose use– Use of lipids and proteins ketosis


B. Tissues involvedB. Adipose

- Fat mobilization- Lipolysis converts triglycerides glycerol + fatty

acids are released into blood- Body cells use them for ATP synthesis- Liver used them for gluconeogenesis

C. Skeletal Muscle- Catabolism of contractile proteins- Release amino acids for use by liver in

gluconeogenesis and ketone body formation


• Most peripheral tissue cells in post absorptive state lacking insulin stimulation– Switch from glucose to ketone bodies for ATP

synthesis• Neurons can only use GLUCOSE

Regulatory Hormones: Effects

on Peripheral Metabolism

Table 25–1

KEY CONCEPT• In the absorption state after a meal:

– cells absorb nutrients to support growth and maintenance– nutrients are stored as energy reserves

• In the postabsorptive state:– gluconeogenesis in the liver maintains blood glucose levels– cells conserve energy by shifting to lipid based metabolism

• If necessary, ketone bodies become preferred energy source• Metabolic shift reserves circulating glucose for use by neurons

What process in the liver would you expect to increase after you have eaten

a high-carbohydrate meal?

A. glycolysis

B. glycogenesis

C. lipolysis

D. beta-oxidation

Why does the amount of urea in blood increase during the

postabsorptive state?

A. Protein digestion creates urea.

B. Lipolysis creates urea.

C. Glycolysis creates urea.

D. Glycogenesis creates urea.

If a cell accumulates more acetyl-CoA than it can metabolize by way of the TCA cycle, what products are likely

to form?

A. ketone bodies

B. uric acid crystals

C. lactic acid molecules

D. ATP molecules

Balanced diet

Homeostasis

• Can be maintained only if digestive tract absorbs enough fluids, organic substrates, minerals, and vitamins to meet cellular demands

Nutrition

• Is the absorption of nutrients from food

• The body’s requirement for each nutrient varies

A Balanced Diet Provides:

• Provides1. Substrates for energy (ATP) production2. Complete proteins (all essential a.a.)3. Essential lipids4. Nitrogen: needed for a.a. and nucleotides5. Minerals = inorganic ions (Ca2+, Na+, etc.)

- Regulation of osmotic conc.- Physiological processes- Cofactors for enzymes- Form compounds

6. Vitamins = organic cofactors

Minerals and Mineral Reserves

Table 25–3

A Balanced Diet Provides: 6. Vitamins = organic cofactors

- Tissue maintenance- Coenzymes- Antioxidants- Hormone and neurotransmitter synthesis*Gut bacteria synthesize K, B5, biotin*Skin synthesizes D3*All other from diet

-Fat soluble (A, D, E, K) stored in fat- too much can cause toxicity

- Water soluble (B, C, niacin, folacin, biotin)- either used or excreted by kidney

The Fat-Soluble Vitamins

Table 25–4

The Water-Soluble Vitamins

Table 25–5

Metabolic rate and what factors are

involved in determining BMR.

Energy Gains and Losses

• Energy is released:– when chemical bonds are broken

• In cells:– energy is used to synthesize ATP– some energy is lost as heat

Bioenergetics

• Study of acquisition and use of energy by organisms

• Measure food energy in Calories• 1 C = 1 kcal = amount of energy needed to

raise temp of 1 kg H2O 1⁰C

• Lipids 9.46 C/g• Carbs 4. 18 C/g• Proteins 4.32 C/g

Bioenergetics• Metabolic Rate

– Sum of all catabolic and anabolic reaction energy needs in body

• Basal Metabolic Rate (BMR)– Minimal energy cost of living to maintain homeostasis– BMR measured 12 hr post food @ 25⁰C room temp

• Average 70 C/hr, 1680 C/day• Increased during healing or pregnancy

– Guestimate:• Weight in kg x 1.0 for males = BMR C/hr• Weight in kg x 0.9 for females = BMR C/hr

Metabolic Rate

• If daily Calorie intake exceeds energy demands:– body stores excess energy as triglycerides in

adipose tissue• If daily caloric expenditures exceeds dietary

supply:– body uses energy reserves (triglycerides)– Loss weight– Loss muscle protein

Hormonal Effects• Thyroxine:

– controls overall metabolism– T4 assay measures thyroxine in blood

• Cholecystokinin (CCK):– suppresses appetite

• Adrenocorticotropic hormone (ACTH):– suppresses appetite

• Leptin:– released by adipose tissues during absorptive state– binds to CNS neurons that suppress appetite

Body Mass Index (BMI)

• BMI = weight in lb x 705 ÷ (height in inches)2

• BMI < 18 = underweight– 18-25 = normal– 25-30 = overweight– > 30 = obese (1:3 Americans)

• Obese = 20% + over ideal body weight• Obese Mouse study

– Leptin k/o mouse obesity– Leptin released by adipocytes to trigger satiation in brain– 5% of obese people have mutation in leptin gene or leptin receptor

Obesity Mouse Study

Heat Production

• BMR estimates rate of energy use• Energy not captured is released as

heat:– serves important homeostatic purpose

• Enzymes operate in a limited temperature range

• Homeostatic mechanisms keep body temperature within limited range (thermoregulation)

Thermoregulation• Body temperature = 97-104⁰F, for enzymes to function• Heat: byproduct of metabolism

– 110⁰F = dead, must lose heat• Heat transfer methods

1.Radiation: infrared waves, ~ 50%2.Conduction: direct heat transfer, low %3.Convection: warm air rises away from skin, cold air gets heated, ~

15%4.Evaporation: water changes to gas vapor using heat energy, ~ 20%,

constant 10% loss due to insensible perspiration

Thermoregulation

• Heat regulation is controlled by anterior hypothalamus– Receptors in skin and brain detect temperature change– Hypothalamus responds via ANS stimulation

• Too hot triggers heat loss1.Peripheral vasodilation incr. radiation & convention2.Sensible perspiration incr. evaporation3.Incr. respiration depth incr. evaporationPyrexia– Elevated temp. if too high heat stroke, cooling mechanism shut

down death

Thermoregulation

• Too cold triggers heat retention and generation1. Constrict cutaneous vessels decr. radiation & convention

Frost bite: if flow restricted for too long tissue dies2. Nonshivering thermogenesis hormones

- Increase metabolic rate (60% of catabolism = heat)3. Shivering thermogenesis muscle contraction

- Increase muscle metabolism incr. heatHypothermia– Low temp. slow metabolism confusion

Thermoregulation• Fever Triggered by pyrogens

– Resets thermostat triggers heat generation to elevate body temperature up to 104⁰F dysfunction, 110⁰F

• Heat and surface area– Volume to surface are ratio affects heat loss and BMR– Incr. area, decr. Volume = incr. heat loss, incr. BMR

• Thin people and children• Infants/small children have Brown Fat

– For heat generation (adipose with mitochondria)– Aerobic respiration produces 60% heat , 40% ATP

Age Related Changes

1. Incr. non-insulin dependent diabetes- Cells ignore insulin and won’t use glucose

2. Incr. glucose in blood can cause permanent protein changes by binding

- cataracts, glaucoma, capillary blockage necrosis3. Decr. Metabolic rate4. Incr. malnutrition due to decr. appetite

How would the BMR of a pregnant woman compare with her own BMR before she

became pregnant?

A. higher when pregnant

B. lower when pregnant

C. no difference during pregnancy

D. impossible to predict

What effect would the vasoconstriction of peripheral blood vessels have on an individual’s body

temperature on a hot day?

A. an increase in body temperature

B. a decrease in body temperature

C. no difference

D. impossible to predict

Why do infants have greater problems with thermoregulation than adults do?

A. higher surface to volume ratio

B. undeveloped temperature regulation

C. expend more energy to remain warm

D. all of the above

SUMMARY• Cellular metabolism• Catabolism• Anabolism• Carbohydrate metabolism• Glycolysis• Cellular Respiration• Mitochondrial ATP production• Gluconeogenesis• Glycogenesis• Lipid catabolism• Beta-oxidation• Lipid synthesis• Lipoproteins

SUMMARY• Amino acid catabolism• Protein synthesis• Metabolic components:

– liver– adipose tissue– skeletal muscle– neural tissue

• peripheral tissues• Absorptive state• Postabsorptive state• Ketone bodies

SUMMARY

• Nutrition• Minerals• Vitamins• Kilocalories (kc)• Calories (c/g)• Metabolic rate• Thermoregulation

Chapter 25: Metabolism Primary sources for figures and content: Marieb, E. N. Human Anatomy &...

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