Marks' Basic Medical Biochemistry - A Clinical Approach 2nd ed - C. Smith, et al., [no index] (Lippincott) WW.pdf
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Marks’ Basic Medical Biochemistry: A Clinical Approach, 2nd Edition
•
Chapter 1: Metabolic Fuels and Dietary Components
•
Chapter 2: The Fed or Absorptive State
•
Chapter 3: Fasting
•
Chapter 4: Water, Acids, Bases, and Buffers
•
Chapter 5: Structures of the Major Compounds of the Body
•
Chapter 6: Amino Acids in Proteins
•
Chapter 7: Structure–Function Relationships in Proteins
•
Chapter 8: Enzymes as Catalysts
•
Chapter 9: Regulation of Enzymes
•
Chapter 10: Relationship Between Cell Biology and Biochemistry
•
Chapter 11: Cell Signaling by Chemical Messengers
•
Chapter 12: Structure of the Nucleic Acids
•
Chapter 13: Synthesis of DNA
•
Chapter 14: Transcription: Synthesis of RNA
•
Chapter 15: Translation: Synthesis of Proteins
•
Chapter 16: Regulation of Gene Expression
•
Chapter 17: Use of Recombinant DNA Techniques in Medicine
•
Chapter 18: The Molecular Biology of Cancer
•
Chapter 19: Cellular Bioenergetics: ATP And O
2
•
Chapter 20: Tricarboxylic Acid Cycle
•
Chapter 21: Oxidative Phosphorylation and Mitochondrial Function
•
Chapter 22: Generation of ATP from Glucose: Glycolysis
•
Chapter 23: Oxidation of Fatty Acids and Ketone Bodies
•
Chapter 24: Oxygen Toxicity and Free Radical Injury
•
Chapter 25: Metabolism of Ethanol
•
Chapter 26: Basic Concepts in the Regulation of Fuel Metabolism by Insulin, Glucagon, and Other
Hormones
•
Chapter 27: Digestion, Absorption, and Transport of Carbohydrates
•
Chapter 28: Formation and Degradation of Glycogen
•
Chapter 29: Pathways of Sugar Metabolism: Pentose Phosphate Pathway, Fructose, and Galactose
Metabolism
•
Chapter 30: Synthesis of Glycosides, Lactose, Glycoproteins and Glycolipids
•
Chapter 31: Gluconeogenesis and Maintenance of Blood Glucose Levels
•
Chapter 32: Digestion and Transport of Dietary Lipids
•
Chapter 33: Synthesis of Fatty Acids, Triacylglycerols, and the Major Membrane Lipids
•
Chapter 34: Cholesterol Absorption, Synthesis, Metabolism, and Fate
•
Chapter 35: Metabolism of the Eicosanoids
•
Chapter 36: Integration of Carbohydrate and Lipid Metabolism
•
Chapter 37: Protein Digestion and Amino Acid Absorption
•
Chapter 38: Fate of Amino Acid Nitrogen: Urea Cycle
•
Chapter 39: Synthesis and Degradation of Amino Acids
•
Chapter 40: Tetrahydrofolate, Vitamin B12, And S-Adenosylmethionine
•
Chapter 41: Purine and Pyrimidine Metabolism
•
Chapter 42: Intertissue Relationships in the Metabolism of Amino Acids
•
Chapter 43: Actions of Hormones That Regulate Fuel Metabolism
•
Chapter 44: The Biochemistry of the Erythrocyte and other Blood Cells
•
Chapter 45: Blood Plasma Proteins, Coagulation and Fibrinolysis
•
Chapter 46: Liver Metabolism
•
Chapter 47: Metabolism of Muscle at Rest and During Exercise
•
Chapter 48: Metabolism of the Nervous System
•
Chapter 49: The Extracellular Matrix and Connective Tissue
SECTION
ONE
Fuel Metabolism
must be able to synthesize everything our cells need that is not supplied by our
diet, and we must be able to protect our internal environment from toxins and
changing conditions in our external environment. In order to meet these
requirements, we metabolize our dietary components through four basic types
of pathways: fuel oxidative pathways, fuel storage and mobilization pathways,
biosynthetic pathways, and detoxification or waste disposal pathways. Cooperation
between tissues and responses to changes in our external environment are commu-
nicated though transport pathways and intercellular signaling pathways (Fig. I.1).
The foods in our diet are the fuels that supply us with energy in the form of calo-
ries. This energy is used for carrying out diverse functions such as moving, think-
ing, and reproducing. Thus, a number of our metabolic pathways are
fuel oxidative
pathways
that convert fuels into energy that can be used for biosynthetic and
mechanical work. But what is the source of energy when we are not eating—
between meals, and while we sleep? How does the hunger striker in the morning
headlines survive so long? We have other metabolic pathways that are
fuel storage
pathways.
The fuels that we store can be molibized during periods when we are not
eating or when we need increased energy for exercise.
Our diet also must contain the compounds we cannot synthesize, as well as all
the basic building blocks for compounds we do synthesize in our
biosynthetic path-
ways.
For example we have dietary requirements for some amino acids, but we can
synthesize other amino acids from our fuels and a dietary nitrogen precursor. The
compounds required in our diet for biosynthetic pathways include certain amino
acids, vitamins, and essential fatty acids.
Detoxification pathways
and
waste disposal pathways
are metabolic pathways
devoted to removing toxins that can be present in our diets or in the air we breathe,
introduced into our bodies as drugs, or generated internally from the metabolism of
dietary components. Dietary components that have no value to the body, and must
be disposed of, are called xenobiotics.
In general, biosynthetic pathways (including fuel storage) are referred to as
ana-
bolic pathways,
that is, pathways that synthesize larger molecules from smaller
components. The synthesis of proteins from amino acids is an example of an ana-
bolic pathway.
Catabolic
pathways are those pathways that break down larger mol-
ecules into smaller components. Fuel oxidative pathways are examples of catabolic
pathways.
In the human, the need for different cells to carry out different functions has
resulted in cell and tissue specialization in metabolism. For example, our adipose
tissue is a specialized site for the storage of fat and contains the metabolic pathways
that allow it to carry out this function. However, adipose tissue is lacking many of
the pathways that synthesize required compounds from dietary precursors. To
enable our cells to cooperate in meeting our metabolic needs during changing con-
ditions of diet, sleep, activity, and health, we need
transport pathways
into the blood
and between tissues and
intercellular signaling pathways.
One means of communi-
cation is for
hormones
to carry signals to tissues about our dietary state. For exam-
ple, a message that we have just had a meal, carried by the hormone insulin, signals
adipose tissue to store fat.
Dietary
components
Fuels:
Carbohydrate
Fat
Protein
Vitamins
Minerals
H
2
O
Xenobiotics
Digestion
absorption,
transport
Compounds
in cells
Biosynthetic
pathways
Fuel storage
pathways
Body
components
Fuel
stores
Detoxification
and waste
disposal
pathways
O
2
Fuel
oxidative
pathways
CO
2
H
2
O
Energy
Waste
products
Fig. I.1.
General metabolic routes for dietary
components in the body. The types of Path-
ways are named in blue.
1
I
n order to survive, humans must meet two basic metabolic requirements: we
In the following section, we will provide an overview of various types of dietary
components and examples of the pathways involved in utilizing these components.
We will describe the fuels in our diet, the compounds produced by their digestion,
and the basic patterns of fuel metabolism in the tissues of our bodies. We will
describe how these patterns change when we eat, when we fast for a short time, and
when we starve for prolonged periods. Patients with medical problems that involve
an inability to deal normally with fuels will be introduced. These patients will
appear repeatedly throughout the book and will be joined by other patients as we
delve deeper into biochemistry.
2
1
Metabolic Fuels and Dietary
Components
Fuel Metabolism
. We obtain our fuel primarily from
carbohydrates, fats
, and
proteins
in our diet. As we eat, our foodstuffs are
digested
and
absorbed
. The
products of digestion circulate in the blood, enter various tissues, and are eventu-
ally taken up by cells and
oxidized
to produce
energy
. To completely convert our
fuels to carbon dioxide (CO
2
) and water (H
2
O), molecular
oxygen
(O
2
) is
required. We breathe to obtain this oxygen and to eliminate the
carbon dioxide
(CO
2
) that is produced by the oxidation of our foodstuffs.
Fuel Stores
. Any dietary fuel that exceeds the body’s immediate energy needs
is stored, mainly as
triacylglycerol
(fat) in adipose tissue, as
glycogen
(a carbohy-
drate) in muscle, liver, and other cells, and, to some extent, as
protein
in muscle.
When we are fasting, between meals and overnight while we sleep, fuel is drawn
from these stores and is oxidized to provide energy (Fig. 1.1).
Fuel Requirements
. We require enough energy each day to drive the
basic
functions
of our bodies and to support our
physical activity
. If we do not con-
sume enough food each day to supply that much energy, the body’s fuel stores
supply the remainder, and we lose weight. Conversely, if we consume more food
than required for the energy we expend, our body’s fuel stores enlarge, and we
gain weight.
Other Dietary Requirements
. In addition to providing energy, the diet provides
precursors
for the
biosynthesis
of compounds necessary for cellular and tissue
structure, function, and survival. Among these precursors are the
essential fatty
acids
and essential
amino acids
(those that the body needs but cannot synthesize).
The diet must also supply
vitamins
,
minerals
, and
water
.
Waste Disposal
. Dietary components that we can utilize are referred to as
nutrients. However, both the diet and the air we breathe contain
xenobiotic com-
pounds
, compounds that have no use or value in the human body and may be
toxic. These compounds are excreted in the urine and feces together with meta-
bolic waste products.
Essential Nutrients
Fuels
Carbohydrates
Fats
Proteins
Required Components
Essential amino acids
Essential fatty acids
Vitamins
Minerals
Water
Excess dietary fuel
Fed
Fuel stores:
Fat
Glycogen
Protein
Fasting
Oxidation
Energy
Fig. 1.1.
Fate of excess dietary fuel in fed and
fasting states.
THE WAITING ROOM
Percy Veere
has a strong will. He is
enduring a severe reactive depres-
sion after the loss of his wife. In
addition, he must put up with the sometimes
life-threatening antics of his hyperactive
grandson, Dennis (the Menace) Veere. Yet
through all of this, he will “persevere.”
Percy Veere
is a 59-year-old school teacher who was in good health until
his wife died suddenly. Since that time, he has experienced an increasing
degree of fatigue and has lost interest in many of the activities he previ-
ously enjoyed. Shortly after his wife’s death, one of his married children moved
far from home. Since then, Mr. Veere has had little appetite for food. When a
3
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