Lingual and Gastric Lipases-Their Role in Fat Digestion

248 Pages·1990·36.447 MB·\248

by  Margit Hamosh (Author)

Lingual and Gastric
Lipases:
Their Role
•
Ill
Fat Digestion
Author
Margit Hamosh, Ph.D.
Professor
and
Chief
Division of Developmental Biology and Nutrition
Department of Pediatrics
Georgetown University Medical Center
Washington, District of Columbia
Boca Raton London New York
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/ dedicate this book to my family:
To my husband Paul for his collaboration, wisdom, and selfless support for
many of the studies described in this book. To my children Ada, Leora,
Tamar, for their love and support. To my mother Clara Segenreich for her
love and guidance and to the memory of my father Dr. Saul Segenreich, who
first introduced me to the beauty of science.
THE AUTHOR
Margit Hamosh, Ph.D., is Professor of Pediatrics and Chief, Division of Developmental
Biology and Nutrition, Department of Pediatrics, Georgetown University Medical Center,
Washington, D.C.
Dr. Hamosh trained at the Hebrew University-Hadassah Medical School, Jerusalem, where
she received her M.Sc. degree in 1956 and her Ph.D. degree in 1959. She served as Assistant
Professor of Biochemistry at the Hebrew University, Hadassah Medical School until 1965,
when she left for sabbatical at the National Institutes of Health (NIMH), Bethesda, MD. After
a 2-year sabbatical she was Visiting Scientist at the National Institute of Health (NI AMD) until
1974, at which time she joined the faculty of Georgetown University Medical Center. She was
appointed Associate Professor of Pediatrics in 1979 and Professor of Pediatrics in 1984. In 1988
she was appointed Chief, Division of Developmental Biology and Nutrition, Department of
Pediatrics, Georgetown University Medical Center.
Dr. Hamosh is a member of the following professional organizations: American Physiologi
cal Society, Society for Experimental Biology and Medicine, Endocrine Society, American
Federation for Clinical Research, American Thoracic Society, New York Academy of Sciences,
Perinatal Research Society, American College of Nutrition, American Women in Science,
American Institute of Nutrition, American Society of Clinical Nutrition, and the International
Society for Research on Human Milk and Lactation.
Dr. Hamosh has served on the Pulmonary Diseases Advisory Committee, National Heart,
Lung and Blood Institute (NIH) 1980 to 1984, and the Maternal and Child Health Research
Committee, NICHD, NIH, 1986 to 1990. Dr. Hamosh was President of the International Society
of Research on Human Milk and Lactation (1987-1989) and is chairing the National Academy
of Sciences Subcommittee on Nutrition during Lactation. She is the first recipient of the Dean's
Prize for Excellence in Research, Georgetown University Medical Center, 1988. She has been
the recipient of research awards from the National Institutes of Health and private industry.
Dr. Hamosh is the author of more than 150 papers and has been co-author of one book. Her
current research interests are fat digestion and absorption, with special emphasis on ontogeny
of digestive enzymes and compensatory digestive function in pancreatic insufficiency; lipid
clearing; the composition of human milk and the function of its components in the newborn
infant.
ACKNOWLEDGMENTS
First and foremost, I thank my secretary, Mrs. Barbara Runner, for her expertise, patience,
wisdom, and excellent sense of humor. Her help was invaluable in preparing this book.
I am very grateful to my former graduate students: Teresa H. Liao, M.D., Ph.D.; Cynthia K.
Abrams, Ph.D.; Stephen J. DeNigris, M.D., Ph.D.; and postdoctoral fellows Carol Fink, Ph.D.,
Sara J. Iverson, Ph.D., and Behjat Alemi, M.D., who have all contributed to the studies cited in
this book. My colleagues, Dr. Judy Barenbaum, Dr. Stanley Benjamin, Dr. Joel Bitman, Dr. Joan
DiPalma, Dr. Sudhir K. Dutta, Dr. Lawrence Grylack, Dr. Van S. Hubbard, Dr. Robert J. Jensen,
Dr. Thomas Lee, Dr. Nitin R. Mehta, Dr. John S. Patton, Dr. John W. Scanlon, Dr. Robert O.
Scow, Dr. K. N. Sivasubramanian, Dr. Yolande Smith, Dr. Michael Spear, Dr. John B. Watkins,
Mr. D. Larry Wood, Mrs. Carla York, and Ms. Charlotte Kirk have contributed greatly, not only
by collaborating in many of the studies described here, but also through stimulating discussions
and ideas.
My thanks to Drs. Peter Berendsen, Arthur R. Hand, Ruth B. Field, I. M. Roberts, R. Verger,
J. S. Patton, F. Testa Riva, and P. Tso for providing illustrations of their studies for this book.
TABLE OF CONTENTS
Introduction... 1
Chapter 1
Historical Background
I. Fat 7
II. Digestion 7
A. Role of Pancreas 8
B. Physical State of Fat during the Absorption Process: The "Particulate" vs.
the "Lipolytic" Theory 8
C. Role of Bile Salts 9
D. Separate Absorption Mechanisms for Long-Chain vs. Medium-Chain
Fatty Acids 9
E. The Different Phases in the Intestine during Fat Absorption 9
F. The Function of the Stomach: William Beaumont's Studies 9
References 12
Chapter 2
Fat Digestion and Absorption
I. Introduction 15
II. The Luminal Phase 15
A. Hydrolysis of Triglyceride 15
1. The Stomach 15
2. The Small Intestine 18
B. Solubilization of the Products of Lipolysis 20
C. Transport to the Enterocyte 21
III. Mucosal Phase 23
A. Intestinal Triglyceride Synthesis and Assembly into Lipoprotein 23
References 29
Chapter 3
Lingual Lipase
I. Introduction 35
II. Oral Lipases 36
III. Source of Lingual Lipase: The Lingual Serous Glands (Von Ebner) 38
IV. Relationship to Taste: Innervation and Enzyme Activities of the Lingual
Serous Glands 39
V. Enzymes Present in von Ebner's Glands 42
VI. Fine Structure of the Lingual Serous Glands and Localization of Lingual Lipase ....42
VII. Ontogeny of the Lingual Serous Glands and of Lipase Activity 51
VIII. Regulation of Secretion of Lingual Lipase 54
IX. Other Factors that Might Affect Enzyme Amount and Secretion 67
A. Effect of Denervation on Lipase Content of Lingual Serous Glands 67
B. Effect of Fat Content of Diet on Lipase Activity in Lingual Serous Glands .. 68
X. Purification of Rat Lingual Lipase 69
XI. Mechanism of Triglyceride Hydrolysis 76
A. Substrate Specificity 76
B. Effect of Fatty Acid Chain Length on Lipolytic Activity 78
C. Stereospecificity 78
XII. Hydrolysis of Phospholipids and Cholesteryl Ester 81
XIII. Effect of pH on the Activity of Lingual Lipase 82
XIV. Stability of Lingual Lipase 83
A. Effect of Temperature 83
B. Effect of pH 86
XV. Effect of Gastrointestinal Environment on Lipase Activity 88
A. Effect of Albumin .88
B. Effect of pH and Procolipase 88
C. Effect of Phospholipid 88
D. Effect of Bile Salts on Lipase Activity 90
XVI. Stability of Lingual Lipase in the Gastrointestinal Environment 94
XVII. Development of Lingual Lipase and of Lipolysis in the Stomach 96
XVIII. Effect of Diverion of Lingual Lipase from the Stomach on Fat Digestion 97
References 99
Chapter 4
Pregastric Esterase
I. Introduction 107
II. Source of Pregastric Esterase 107
III. Purification of Pregastric Esterase 108
IV. Characteristics of Pregastric Esterase Activity 112
A. pH Optimum, pH Stability, Optimal Reaction Temperatures, and Substrate
Specificity 112
V. Physiological Factors that Affect the Activity of Pregastric Esterase 116
A. Age 116
B. Diet 117
C. Nursing vs. Drinking 117
VI. Is There a Gastric Lipase in Ruminants? 117
VII. Role of Pregastric Esterase in Fat Digestion and Absorption 119
VIII. Antiinfective Function of Pregastric Esterase 123
Acknowledgment 124
References 124
Chapter 5
Gastric Lipase
I. Introduction 127
II. Historical Overview 128
III. Species Differences in the Origin of Prepancreatic Lipases 132
IV. Localization of Gastric Lipase 135
A. Species other than the Human 135
V. Localization of Pepsin in the Stomach of Different Species 137
VI. Localization of Lipase in the Human Stomach 139
VII. Effect of Age on the Activity of Gastric Lipase 140
VIII. Use of Isolated Gastric Glands for the Study of the Mechanism of Secretion of
Gastric Lipase (Animal and Human Studies) 143
IX. Characteristics of the Lipase in Human Gastric Juice and Mucosal Homogenates. 149
A. Molecular Weight 150
B. pH Optimum 150
C. Substrate Specificity 152
1. Chain Length 152
2. Stereospecificity 153
3. Reaction Products Formed during Triglyceride Hydrolysis of
Gastric Lipase 153
4. Lipid Class 153
D. Effect of Fatty Acid Acceptor 153
E. Effect of Bile Salts 157
F. Effect of Phospholipids 157
G. Stability of Gastric Lipase 158
X. Purification of Gastric Lipase 158
A. Characteristics of the Purified Lipase 158
XL Cloning of Human Gastric and Rat Lingual Lipases 166
References 172
Chapter 6
Role of Lingual and Gastric Lipases in Fat Digestion and Absorption
I. Introduction 179
II. Role of Lingual and Gastric Lipases in the Neonatal Period 179
A. Digestion of Milk Fat 179
1. Structure and Composition of Milk Fat 180
2. The Milk Fat Globule 181
3. Fat Classes 181
4. Fatty Acid Composition 182
5. Preduodenal Digestion of Milk Fat 183
a. Lingual Lipase 183
b. Gastric Lipase 185
c. Milk Digestive (Bile Salt-Stimulated) Lipase 189
d. Role of the Combined Action of Gastric and Milk Digestive
Lipases in the Digestion of Milk Fat in the Newborn 191
6. Fat Digestion in the Newborn Infant 193
a. Medium-Chain Triglycerides 193
b. The Gastric Milieu of the Newborn Infant 198
c. Effect of Mode of Feeding on Lipase Activity in the
Stomach 198
i. Effect of Nonnutritive Sucking 199
ii. Effect of Total Parenteral Nutrition 202
III. Role of Lingual and Gastric Lipases in Fat Digestion in Pancreatic
Insufficiency 203
A. Cystic Fibrosis 203
B. Chronic Alcoholism 210
1. Total Nonpancreatic Lipolytic Activity at the Ligament of Treitz .... 210
2. Total Lipolytic Activity (Pancreatic and Nonpancreatic) Delivered
to the Ligament of Treitz 211
IV. Role of Lingual and Gastric Lipases in Fat Digestion in Normal Conditions 211
V. Conclusions 216
VI. Directions for Future Research 219
References 219
Addendum 229
Index 233
1
INTRODUCTION
Fats supply more than 40% of the total calories in western industrial societies.1 Fats are
essential for normal cellular structure and function. They are also vital for normal growth and
development. In addition to providing 40 to 50% of the toal calories in human milk or formula,
fats are essential during development because they provide fatty acids necessary for brain
development, are an integral part of all cell membranes, and are the sole vehicle for fat-soluble
vitamins and hormones in milk. Furthermore, these energy-rich lipids can be stored in the body
in nearly unlimited amounts in contrast to the limited storage capacity for carbohydrates and
proteins. However, before it can be assimilated, dietary fat has to be digested. In general terms
the digestion and absorption of fat involves essentially the transport of water-insoluble
molecules from one water phase, the lumen of the gastrointestinal tract, to another water phase,
the lymph and plasma. The solubility characteristics of the different lipid classes are therefore
essential properties for their interaction with lipolytic enzymes during the process of digestion
and with the cell membrane during the absorption process.
I would like to start with definitions of the terms lipid and lipase. According to the Dorland
Medical Dictionary:2 Lipid (derived from the Greek lipos = fat) is "any of a heterogenous group
of fats and fat like substances characterized by being water-insoluble and being extractable by
nonpolar (or fat) solvents such as alcohol, ether, chloroform, benzene, etc. All contain as a major
constituent aliphatic hydrocarbons. Lipids may be considered to include fatty acids, waxes and
steroids. Compound lipids comprise the glycolipids, lipoproteins, and phospholipids." The
Dorland Medical Dictionary,2 however, narrows the definition of fat to: "an ester of glycerol
with fatty acids, usually oleic acid, palmitic acid, or stearic acid, triacylglycerol, neutral fat."
LIPASE IS DEFINED AS
"Glycerol ester hydrolase; any of a group of widely occurring enzymes that catalyze the
hydrolysis of ester linkages between the fatty acids and glycerol of the triglycerides and
phospholipids." This book will deal mainly with the role of lingual and gastric lipases in the
digestion of dietary fat. Thus, the substrate is indeed fat as defined above. However, because
some of the other lipids (such as cholesteryl ester and phospholipid) will sometimes be briefly
mentioned, I have included them in the following lipid glossary.
GLOSSARY
GLYCERIDES
Glycerides and nonphosphorus-containing lipids which result from the esterification of
glycerol and fatty acids (Figure 1). Three forms occur in nature. Triglycerides (neutral fat) are
the most abundant lipids in animal tissue and serve as an important energy source. All three of
the carbon molecules of glycerol are sterified with fatty acids. Monoglycerides and diglycerides
are compounds resulting from ester links between glycerol and one or two fatty acids.
PHOSPHOLIPIDS
Phospholipids, phosphorus-containing lipid compounds, may be subdivided into three
clases: ( 1 ) derivatives of glycerol-3-phosphate (phosphatidyl choline, phosphatidyl ethanolam-
ine, phosphatidyl serine, and phosphatidyl inositol), sphingosine, and the glycoplipids. Phospho
lipids are found as structural components of all biological membranes. They are important in
oxidative phosphorylation, in transport across cell membranes, and in electron transport
reactions.
STEROLS
Sterols are alcohols with the cyclopentanoperhydrophenanthrene skeletal structure. The