Table Of ContentNutrient Metabolism
Structures, Functions, and Genes
Nutrient Metabolism
Structures, Functions, and Genes
Second Edition
Martin Kohlmeier
Research Professor,
Department of Nutrition,
UNC Gillings School of Global Public Health,
and UNC Nutrition Research Institute,
University of North Carolina,
USA
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Second edition 2015
First edition 2003
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Preface
It has been twelve years since the first edition of Nutrient Metabolism was published. That was also the
year when a first read of our genome was completed and the blueprint for all human existence was deci-
phered. Since then many of the formerly white areas in the vast expanses of the nutrient metabolism
map have been colored in. We now know much more about the metabolic fates of nutrients and about
the molecular actors and mechanisms responsible for the underlying processes. A major reason for the
explosive advances in the understanding of nutrient metabolism has been the massive investigative use
of all kinds of “-omics”.
One of these high-resolution technologies is genomics. We now know most genes. A few may still
play hard to get, but there are not going to be a lot of surprises. The attention, therefore, has turned
increasingly to the multiple products individual genes can generate, how their production is regulated,
and what the gene products actually do. High-throughput analyzers, which can read millions of DNA or
RNA bases in days, have made it possible to study genes and their expression in detail in many differ-
ent species of model animals and in human populations. Who would have thought that the blood group
secretor status is a major determinant of vitamin B12 sufficiency in older adults? A wave of genome-
wide association studies has yielded this and many other new and often unexpected insights into the
inner workings of nutrient metabolism.
We can also use epigenomics to monitor in detail many chemical modifications of particular DNA
sequences. The most widely known kind, the methylation of cytosine bases in promoter regions, will
usually silence expression of the associated gene. Each cell type has its own set of characteristic epi-
genetic modifications that determine the nature of the cells and what they do. While many methyla-
tion patterns are tissue specific, others are shared more globally and can be read from blood cells.
Several nutrients are important for the epigenetic status at numerous DNA sites of interest because
they are needed for a steady supply of methyl groups. Research in recent years has greatly increased
our understanding of the relevant pathways, variation of the involved genes, and the role of nutrients,
phytochemicals, and feeding status in setting epigenetic patterns.
The advances in proteomics also had their share in deepening the understanding of nutrient metabo-
lism. Proteomic analyses, which resolve proteins and peptides from different tissues and cell lines with
high-resolution techniques, have concluded that fewer than 20,000 genes are coding for proteins. The
approach has helped to clarify in which tissues particular proteins are present and contribute to nutrient
metabolism there.
Many of the new insights have come from metabolomic analyses. This approach measures many
different small metabolites in fluids and tissues. Current technologies already can resolve several thou-
sand different compounds and this number is rapidly growing. The distinct compounds in foods and the
metabolic products derived from them most likely are more than one hundred thousand in number. For
example, the consumption of a particular fruit juice leads to a signature increase in urine of urolithin A
glucuronide, pyrogallol sulfate, and ascorbic acid sulfate, which can be linked to their specific precur-
sors, ellagitannins and ascorbic acid. Being able to make sense of food- and nutrient-specific metabolite
patterns is becoming increasingly important. An understanding of the nature of food constituents, their
properties, and typical metabolic conversions helps with the interpretation of complex chemical signa-
tures in biological fluids.
xi
xii Preface
The role of gut bacteria explored by microbiomics, for nutrient metabolism did not receive much
attention when the first edition was put together, but this aspect absolutely had to be added now. The
human intestines contain about ten times as many microorganisms as there are cells in the human body
taken together. The collection of bacteria, yeasts, and viruses in the intestinal tract constitute the human
gut microbiome. Many microbiota are metabolically very active. They partake of the food that comes
their way, convert some of the dietary fiber into fuels for their host, and provide essential vitamins.
They also chemically alter bile acids and other compounds in the intestinal lumen before they are
absorbed. Thus, the gut microbiome functions like a chemical factory that is normally well integrated
into overall human metabolism and critically important for good health. The shifts in the balance of
many nutrients due to disruption of the microbiome by dietary factors, infections, or antibiotics are
increasingly recognized, opening up new approaches for prevention and treatment of diseases.
All those advances in nutrition science notwithstanding, most of what we have known at the time of
the first edition has not changed. On the positive side, there have been few fundamental surprises and
much of the emerging new information is consistent with previously established science. On the nega-
tive side, the paradigms and dogmas governing practice and policies are notoriously slow to change
and that is particularly true for nutrition. For example, every word in the first edition about setting the
Dietary Recommended Intakes (DRI) is as applicable now as it was then. Despite our rapidly growing
recognition of extensive genomic and metabolic diversity even within seemingly homogenous popula-
tions, current intake recommendations still assume that everybody has more or less the same metabo-
lism. This is certainly contradicted by the known genomic, proteomic, metabolomic, and microbiomic
variations that make each of us different, sometimes very different. The smallest structural difference in
an enzyme, transporter, or receptor can profoundly change its function and alter how much of a nutrient
a carrier needs. Similarly, common epigenetic alterations of our genome and subtle shifts in microbi-
ome patterns have important nutritional implications. The information in this book is meant to help put
the nutritional consequences of such functional differences into perspective.
Martin Kohlmeier
Chapel Hill, April 2015
Acknowledgments
I am indebted to many people for their support, encouragement, and helpful discussions while work-
ing on this new edition. The support and collaborative environment of the UNC Nutrition Research
Institute has been particularly helpful. I also could not have done this without the consistent and caring
support of the Nutrition in Medicine team at the University of North Carolina at Chapel Hill.
xiii
List of Abbreviations
1,25-(OH)2-D 1,25-dihydroxyvitamin D
1,25-D 1α,25-dihydroxyvitamin D
1,7-X 1,7-dimethylxanthine
24,25-D 24R,25-dihydroxyvitamin D
25-D 25-hydroxyvitamin D
25-OH-D 25-trihydroxyvitamin D
5-HT 5-hydroxytryptamine
5-HTOL 5-hydroxytryptophol
6-SMT 6-sulfatoxymelatonin
A2S ascorbate-2-sulfate
ABC ATP-binding cassette (ABCA1, ABCG5, ABCG8)
ADH alcohol dehydrogenase (Chapters 6, 9, and 12)
ADH antidiuretic hormone (Chapters 1, 3, and 11)
ADPR ADP ribose
AgRP agouti-related protein
AI Adequate Intake
AI-2 autoinducer 2
AK adenylate kinase
Ala l-alanine
ALDH aldehyde dehydrogenase
AMP adenosine monophosphate
AMPK AMP-activated protein kinase
ANP atrial natriuretic peptide
apBGlu p-acetamidobenzoylglutamate
apoAI apolipoprotein AI
apoAII apolipoprotein AII
apoAIV apolipoprotein AIV
apoB apolipoprotein B
apoB48 apolipoprotein B48
apoB100 apolipoprotein B100
apoC-I apolipoprotein C-I
apoC-II apolipoprotein C-II
apoC-III apolipoprotein C-III
apoE apolipoprotein E
APS adenosine 5'-phosphosulfate
AQP aquaporin
Arg l-arginine
As arsenic
ASC l-ascorbic acid
Asn l-asparagine
Asp l-aspartate
ATP7A copper-transporting ATPase (ATP7A, ATP7B)
xv
xvi List of Abbreviations
B boron
B6 vitamin B6
B12 vitamin B12
BBB blood–brain barrier
BCAA branched chain amino acids
BGT1 sodium chloride–dependent betaine transporter
BH4 5,6,7,8-tetrahydrobiopterin
BM basal membrane
Br bromine
CACT carnitine-acylcarnitine translocase
cADPR cyclic ADP-ribose
cAMP cyclic adenosine monophosphate
Carbs carbohydrates
CaSR calcium-sensing receptor
CAT-2 cationic amino acid transporter 2
CCK cholecystokinin
CD Celiac disease
CFTR cystic fibrosis transmembrane regulator
Chol cholesterol
Chylos chylomicrons
CLA conjugated linoleic acid
CLD congenital diarrhea gene
Co cobalt
CoA coenzyme A
Cr chromium
CRBP2 cellular retinol–binding protein 2
CSF cerebrospinal fluid
CssC l-cystine
CTR copper transporter (CTR1, CTR2)
CYP cytochrome P450
Cys l-cysteine
D2 vitamin D2
D3 vitamin D3
DADS diallyl disulfide
DADSO diallyl thiosulfinate
DATS diallyl trisulfide
DBP vitamin D–binding protein
DHA dehydro-l-ascorbic acid (Chapter 10)
DHA docosahexaenoic acid (Chapters 3, 5, 12)
DHF dihydrofolate
DiMelQx 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline
DL-AP4 DL(+)-2-amino-phosphono-butyric acid
DMA(III) dimethylarsinous acid
DMA(V) dirnethylarsinic acid
DMT1 divalent metal ion transporter 1
List of Abbreviations xvii
DPDS dipropyl disulfide
DRA down-regulated in adenoma gene
DRI Dietary Reference Intake
DTDST diastrophic dysplasia sulfate transporter
EAR Estimated Average Requirement
ECaC1 epithelial calcium channel 1
ECI enoyl-CoA isomerase
EMS eosinophilia-myalgia syndrome
EPA eicosapentaenoic acid
ETF electron-transfer flavoprotein
F fluorine
F6P fructose 6-phosphate
FABPpm plasma membrane fatty acid binding protein
FAD flavin adenine dinucleotide
FATP-1 fatty acid transport protein 1
FIGLU formiminoglutarnate
FMN flavin mononucleotide
FOLR folate receptor (FOLR1, FOLR2, FOLR3)
Fru d-fructose
GABA gamma-aminobutyric acid
Gal d-α-galactose
GalNAc Gal N-acetylglucosamine
GAP glyceraldehyde 3-phosphate
GFR Glomerular Filtration Rate
GIc d-glucose
Gln l-glutamine
GLP-1 glucagon-like peptide 1
Glu l-glutamate
GLUT glucose transporter (GLUT1, GLUT2, GLUT3, GLUT4, GLUT5)
Glvr-1 gibbon ape leukemia virus receptor
Gly glycine
GMP guanosine-5′-monophosphate
Grp120 G-protein coupled receptor 120
GSH glutathione
HA heterocyclic amine
Hcys homocysteine
HDL high-density lipoprotein
HFE hemochromatosis gene
HIF-1 hypoxia-inducible factor 1
His l-histidine
HMGCoA hydroxymethylglutaryI-CoA
HNE 4-hydroxy-2,3-trans-nonenal
Hypro 4-hydroxyproline
