1. 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.

2. Metabolism
Digestion + Absorption by GI  monomers (building blocks) for ATP or biomolecule synthesis
Metabolism = sum of all chemical reactions in the body

3. Metabolism
Figure 25–1

4. Metabolism Catabolism Breakdown of organic molecules Hydrolysis
- Large molecules into monomers
Cellular Respiration
Oxidation of monomers in mitochondria
40% of energy  ATP
60% of energy  heat
Anabolism
Synthesis of new organic molecules for
Cell maintenance and repair & Growth
Formation of secretions & Nutrient reserves

5. Nutrient Use in Cellular Metabolism
Catabolism supplies ATP and monomers to drive anabolism
Figure 25–2 (Navigator)

6. Carbohydrate Metabolism

7. Carbohydrate Metabolism
Carbs are easiest to catabolize for energy, always used first
Cellular respiration
Oxidizes glucose + oxygen  carbon dioxide + water and generates ATP

8. Cellular Respiration Review 1. Glycolysis
Figure 25–3 (Navigator)

9. Cellular Respiration Review 1. 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

10. Cellular Respiration Review 2. Decarboxylation + Kreb/Citric Acid Cycle
Figure 25–4a (Navigator)

11. Cellular Respiration Review 2. Decarboxylation + Kreb/Citric Acid Cycle
Figure 25–4b

12. Cellular Respiration Review 2. Decarboxylation + Kreb/Citric Acid Cycle
Occur in matrix of mitochondria
Decarboxylation:
2 pyruvic acid decarboxylated and oxidized into  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  CO2, 6 NADH, 2 FADH2
2 ATP generated by substrate level phosphorylation

13. Cellular Respiration Review 3
Cellular Respiration Review 3. Electron Transport Chain/Oxidative Phosphorylation
Figure 25–5a (Navigator)

14. Cellular Respiration Review 3
Cellular Respiration Review 3. Electron Transport Chain/Oxidative Phosphorylation
Figure 25–5b

15. Cellular Respiration Review 3
Cellular Respiration Review 3. Electron Transport Chain/Oxidative Phosphorylation
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

16. Summary: Complete Aerobic Cellular Respiration
With Oxygen
1 glucose =36 ATP
Without Oxygen
1 glucose = 2 ATP
(0 ATP in neurons
and cardiac muscle,
where fermentation
is not possible)
Figure 25–6

17. Carbohydrate Metabolism
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

18. Carbohydrate Metabolism
3. Functions of Glucose
Stored as glycogen via Glycogenesis
Used to generate ATP
To create other carbohydrates
Cell membrane receptors
Nucleic acids

19. Carbohydrate Breakdown and Synthesis
Figure 25–7

20. Lipid Metabolism

21. Lipid Metabolism 1. Lipid Catabolism Triglycerides are most common
Lipolysis
Triglycerides  glycerol + 3 fatty acids
A. Glycerol  pyruvic acid  citric acid cycle  generate 18 ATP
B. 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

22. Beta–Oxidation
Figure 25–8 (Navigator)

23. 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

24. Lipid Metabolism 2. Lipid Anabolism A. 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

25. Lipid Metabolism Lipid Anabolism C. Essential Fatty Acids
Must be ingested in diet, no synthesis
1. Linolenic acid = Omega 3 fatty acid
2. Linoleic acid = Omega 6 fatty acid
**Both used to synthesize arachidonic acid, to synthesize eicosanoids (leukotrienes and protaglandins), for cell signaling

26. Lipid Metabolism 3. 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

27. 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

28. Lipoprotein Classes Increased lipids = decreased density
1. 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

29. Lipoprotein Classes Increased lipids = decreased density
4. Low Density Lipoproteins
High cholesterol, low triglycerides and phospholipids
Deliver cholesterol from liver to tissues
5. High Density Lipoproteins
Equal protein and lipids (cholesterol and phospholipids
Return cholesterols to liver for degradation

30. Lipoprotein Distribution
Liver synthesizes VLDLs and releases them into blood
Triglycerides are removed in capillaries making IDLs from the VLDLs
IDLs return to liver, triglycerides are removed and proteins are altered, making LDLs from the IDLs which are released to blood
LDLs travel to peripheral tissues
Cells endocytose LDLs and break them down
Extra cholesterol diffuses out of the cells and enters the blood

31. Lipoprotein Distribution
Cholesterol binds to HDLs in blood and returns to liver
HDLs at liver have cholesterol extracted to form
empty HDLs,
new LDLs,
and bile salts
Empty HDLs return to the blood to pick up free cholesterol

32. Lipid Transport and Utilization
Figure 25–9

33. 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

34. Protein Metabolism

35. 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

36. Protein Metabolism 1. 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!

37. Protein Metabolism 1. Amino Acid Catabolism

38. Protein Metabolism 2. Amino Acid Anabolism A. 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 lbs of protein in our lifetime

39. Protein Metabolism 2. Amino Acid Anabolism
Figure 25–11

40. Phenylketonuria Lack of enzyme to convert phenylalanine to tyrosine
Tyrosine is needed for melanin
Deaminated phenylalanine levels rise  neurotoxic affects

41. Protein Metabolism 3. Functions of Proteins Cell structural components
Enzymes
hormones

42. Summary: Pathways of Catabolism and Anabolism
Figure 25–12

43. Nucleic Acid Metabolism

44. 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

45. Gout
Crystals of uric acid in joints
Causes pain and swelling

46. How would a diet that is deficient in pyridoxine (vitamin B6) affect protein metabolism?
It would interfere with protein metabolism.
It would enhance protein metabolism.
It would cause the use of different coenzymes.
Pyridoxine is not involved in protein metabolism.

47. Elevated levels of uric acid in the blood can be an indicator of increased metabolism of which organic compound?
nucleic acids
proteins
carbohydrates
lipids

48. Why are high-density lipoproteins (HDLs) considered beneficial?
They increase lipid metabolism.
They decrease blood pressure.
They increase blood pH.
They reduce fat and cholesterol in the bloodstream.

49. 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
Has contractile proteins that can be catabolized

50. 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

51. Patterns of Metabolic Activity
The Absorptive State
- Anabolism exceeds catabolism
The Post Absorptive State
- Catabolism dominates

52. 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 reserves
A. Hormones involved
Insulin:
- promotes glucose uptake and utilization by cells
Growth hormone:
- promotes amino acid uptake and protein synthesis by cells
Androgens and Estrogens :
- promote amino acid utilization in protein synthesis

53. 1. Absorptive State B. Tissues involved 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

54. 1. Absorptive State B. Tissues involved 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
Peripheral Tissues:
Absorb glucose for ATP synthesis
Absorb amino acids for protein synthesis

55. 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

56. 2. Post Absorptive State A. Hormones involved Glucagon
- Promotes release of glucose from liver
Epinephrine
Promotes release of glucose from liver
Promotes lipolysis in adipose and release of glycerol and fatty acids
Glucocorticoids
Inhibits use of glucose of body tissues
Promotes use of fatty acids
Growth Hormone: Complements glucocorticoids
*Blood glucose decr. glucagon + epinephrine incr., insulin decr.

57. 2. Post Absorptive State B. Tissues involved 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

58. 2. Post Absorptive State B. Tissues involved 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

59. Ketosis 1. During Starvation 2. Diabetes mellitus
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 disease
2. Diabetes mellitus
No insulin  no glucose use
Use of lipids and proteins  ketosis

60. 2. Post Absorptive State B. Tissues involved 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
Skeletal Muscle
Catabolism of contractile proteins
Release amino acids for use by liver in gluconeogenesis and ketone body formation

61. 2. Post Absorptive State
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

62. Regulatory Hormones: Effects on Peripheral Metabolism
Table 25–1

63. 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

64. What process in the liver would you expect to increase after you have eaten a high-carbohydrate meal?
glycolysis
glycogenesis
lipolysis
beta-oxidation

65. Why does the amount of urea in blood increase during the postabsorptive state?
Protein digestion creates urea.
Lipolysis creates urea.
Glycolysis creates urea.
Glycogenesis creates urea.

66. If a cell accumulates more acetyl-CoA than it can metabolize by way of the TCA cycle, what products are likely to form?
ketone bodies
uric acid crystals
lactic acid molecules
ATP molecules

67. Balanced diet

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

69. Nutrition Is the absorption of nutrients from food
The body’s requirement for each nutrient varies

70. A Balanced Diet Provides:
Substrates for energy (ATP) production
Complete proteins (all essential a.a.)
Essential lipids
Nitrogen: needed for a.a. and nucleotides
Minerals = inorganic ions (Ca2+, Na+, etc.)
Regulation of osmotic conc.
Physiological processes
Cofactors for enzymes
Form compounds
Vitamins = organic cofactors

71. Minerals and Mineral Reserves
Table 25–3

72. 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

73. The Fat-Soluble Vitamins
Table 25–4

74. The Water-Soluble Vitamins
Table 25–5

75. Metabolic rate and what factors are involved in determining BMR.

76. 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

77. 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  C/g
Proteins  4.32 C/g

78. 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 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

79. 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

80. Hormonal Effects Thyroxine: controls overall metabolism
T4 assay measures thyroxine in blood
Cholecystokinin (CCK):
suppresses appetite
Adrenocorticotropic hormone (ACTH):
Leptin:
released by adipose tissues during absorptive state
binds to CNS neurons that suppress appetite

81. 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

82. Obesity Mouse Study

83. 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)

84. Thermoregulation Body temperature = 97-104⁰F, for enzymes to function
Heat: byproduct of metabolism
110⁰F = dead, must lose heat
Heat transfer methods
Radiation: infrared waves, ~ 50%
Conduction: direct heat transfer, low %
Convection: warm air rises away from skin, cold air gets heated, ~ 15%
Evaporation: water changes to gas vapor using heat energy, ~ 20%, constant 10% loss due to insensible perspiration

85. 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 loss
Peripheral vasodilation  incr. radiation & convention
Sensible perspiration  incr. evaporation
Incr. respiration depth  incr. evaporation
Pyrexia
Elevated temp. if too high  heat stroke, cooling mechanism shut down  death

86. Thermoregulation Too cold  triggers heat retention and generation
Constrict cutaneous vessels  decr. radiation & convention
Frost bite: if flow restricted for too long  tissue dies
Nonshivering thermogenesis  hormones
- Increase metabolic rate (60% of catabolism = heat)
Shivering thermogenesis  muscle contraction
- Increase muscle metabolism  incr. heat
Hypothermia
Low temp.  slow metabolism  confusion

87. 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

88. Age Related Changes Incr. non-insulin dependent diabetes
- Cells ignore insulin and won’t use glucose
Incr. glucose in blood can cause permanent protein changes by binding
- cataracts, glaucoma, capillary blockage  necrosis
Decr. Metabolic rate
Incr. malnutrition due to decr. appetite

89. no difference during pregnancy
How would the BMR of a pregnant woman compare with her own BMR before she became pregnant?
higher when pregnant
lower when pregnant
no difference during pregnancy
impossible to predict

90. an increase in body temperature a decrease in body temperature
What effect would the vasoconstriction of peripheral blood vessels have on an individual’s body temperature on a hot day?
an increase in body temperature
a decrease in body temperature
no difference
impossible to predict

91. Why do infants have greater problems with thermoregulation than adults do?
higher surface to volume ratio
undeveloped temperature regulation
expend more energy to remain warm
all of the above

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

93. SUMMARY Amino acid catabolism Protein synthesis Metabolic components:
liver
adipose tissue
skeletal muscle
neural tissue
peripheral tissues
Absorptive state
Postabsorptive state
Ketone bodies

94. SUMMARY Nutrition Minerals Vitamins Kilocalories (kc) Calories (c/g)
Metabolic rate
Thermoregulation