18
Mineral Metabolism
E. Kebreab
1
and D.M.S.S. Vitti
2
1
Centre for Nutrition Modelling, Department of Animal & Poultry Science,
University of Guelph, Guelph, Ontario, N1G 2W1, Canada;
2
Animal Nutrition
Laboratory, Centro de Energia Nuclear na Agricultura, Caixa Postal 96, CEP
13400-970, Piracicaba, SP, Brazil
Introduction
The number of mineral elements that have been shown to have essential
functions in the body has been increasing steadily since the 1950s. Major or
macrominerals are required in relatively larger quantities (>50 mg=(kg DM)) and
include calcium, phosphorus, potassium, sodium, sulphur, chlorine and mag-
nesium. Trace or microminerals include iron, zinc, copper, molybdenum, sel-
enium, iodine, manganese, cobalt, chromium, fluorine, arsenic, boron, lead,
lithium, nickel, silicon, tin and vanadium. Due to lack of space, all the minerals
and their quantitative aspects of metabolism cannot be discussed in detail here.
As in the previous edition of the book, we chose to focus on quantitative aspects
of two minerals. From the macro elements, phosphorus is taken as an example
mainly because it is the element which has been a subject of much research in
recent years due to concerns of overfeeding phosphorus to ruminants and the
contribution to environmental pollution. The principles outlined are also applic-
able to other macrominerals such as calcium. A model of magnesium metabol-
ism in sheep was developed by Robson et al. (1997) and modified by Bell et al.
(2005) which followed similar principles. Symonds and Forbes (1993) took
copper as an example of trace elements and discussed its metabolism. Although

Quantitative aspects of P metabolism in ruminants have been considered using
balance studies (e.g. Braithwaite, 1983), kinetic models based on experiments
in which radioactive tracers were used (e.g. Vitti et al., 2000), compartmental
(e.g. Schneider et al., 1987) and mechanistic models (Symonds and Forbes,
1993; Kebreab et al., 2001, 2004). These mathematical approaches used in
investigating P metabolism in ruminants can be broadly classified into empirical
and mechanistic types of modelling. For example, approaches based on re-
gression analysis (e.g. efficiencies of utilization of P as determined by
Braithwaite, 1983) are empirical while mechanistic approaches are process-
based such as the dynamic model presented in this chapter. Mechanistic models
can be of three types depending on the solutions of the equation statements
(see Dijkstra et al., 2002). In steady state, Type I models obtain solutions by
setting differentials to zero and manipulating to give algebraic expressions for
each process (e.g. model reported by Vitti et al., 2000). In non-steady state,
Type II models solve rate:state equations analytically. Type III models solve
complex cases of rate:state equations numerically in non-steady state (e.g.
model developed in this chapter). Most models used for P analysis in ruminants
are Type I and III. In the following paragraphs, examples of empirical models
are discussed first, followed by kinetic models and finally the mechanistic
P model of Kebreab et al. (2004) will be slightly modified and evaluated.
Empirical models
Most of the models for calculating P requirements are based on a factorial ap-
proach by adding requirements for various physiological processes such as main-
470 E. Kebreab and D.M.S.S. Vitti
tenance, growth, pregnancy and lactation. Such models compute the require-
ment of an animal for minerals for a predetermined level of production.
Most European and American national standards for requirements of P are
based on this approach. For example, in NRC (2001), absorbed P requirement
for maintenance for growing animals was calculated to be 0.8 g/kg DMI (with
0.002 g/kg W allowance for urinary P) based on P balance studies. AFRC

rumen, abomasum and upper small intestine, lower small intestine, caecum and
colon and kidney. Analysis of
32
P tracer data was conducted using a
compartmental analysis computer program (Boston et al., 1981). Schneider
et al. (1987) reported that the main control site for P excretion was the
gastrointestinal tract and model predictions were sensitive to the parameters
describing absorption or salivation. In ruminants, a substantial amount of P is
recycled through saliva. Salivation rate was also found to be a major controlling
factor in urinary P excretion: decreasing salivation rate increased P
concentrations in plasma and resulted in more P being excreted via urine.
Using data from balance and kinetic studies, a model of P metabolism in
growing goats fed increasing levels of P was proposed by Vitti et al. (2000)
(Fig. 18.1). The model has four pools (gut (1), blood (2), bone (3) and soft
tissues (4)) and P enters the system via intake (F
10
) and exits via faeces (F
01
) and
urine (F
02
). The daily intake and loss of P in faeces and urine were measured by
chemical analysis. Endogenous P and P absorption were calculated from the
specific activities (Vitti, 1989). The gut lumen, bone and soft tissue pools
interchange bidirectionally with the blood pool, with fluxes F
21
and F
12
, F
23

diets. At low P intakes, bone and tissue mobilization represented a vital process
to maintain P levels in blood. Vitti et al. (2002) also adapted the model to
illustrate the different processes that occur in goats fed various Ca levels and
showed that Ca intake influenced absorption, retention and excretion of Ca
(Vitti et al., 2002). The model could be used to investigate P metabolism not
only in goats but also in other ruminants as well.
Grace (1981) used a compartmental P model to represent P flow in sheep.
The model was comprised of four compartments which together represent the
total exchangeable P pool (M
T
), the gut and non-exchangeable bone and soft
tissues. Phosphorus flow to M
T
is from the gut and in a steady state is equal to
the outflow. The outflow of P from the total pool consists of the urinary P,
faecal endogenous loss of P, P deposition into non-exchangeable bone and the
4
1
2
3
F
10
F
01
F
12
F
21
F
23

.
A dynamic P model of Kebreab et al.
(2004) integrating information from various sources including the flow diagram
described by Symonds and Forbes (1993) and the state variables of Vitti et al.
(2000) is modified. The fluxes between pools and excretion parameters are
estimated based on a wide range of sources. Sensitivity of selected parameter
estimates were carried out and the model was then tested on independent data
that were not used in the construction of the model. For clarity, the model can
be seen as having four P compartments: rumen, small intestine (including
duodenum), large intestine and extracellular fluid. In total, the model contains
11 state variables or pools, and arrows (Fig. 18.2) represent inputs and outputs
to and from the pools. The standard cow was assumed to weigh 600 kg with a
rumen volume of 90 l and non-pregnant. The input of P to the cow is via the
diet and the outputs are in faeces, urine and milk.
The simulation model uses the dynamic rumen model of Dijkstra et al.
(1992) and its subsequent modification (Dijkstra, 1994) to estimate rumen
microbial synthesis and microbial outflow to the duodenum. In the rumen,
two forms of P are represented based on digestibility. The digestible rumen P
pool has two inputs, from the diet and saliva. P is consumed by the animal as
organic (phytates, phospholipids and phosphoproteins) and inorganic P
(mono-, di- and triphosphates). Soluble forms, some insoluble forms and phos-
phoric acid are dissolved by digestive juices in the rumen. Phytate is dissolved in
the rumen by action of phytases produced by the microbes. The availability of P
in the diet has been the subject of many investigations (e.g. Koddebusch and
Pfeffer, 1988). ‘True absorption’ coefficients have been used to describe the
amount of dietary P absorbed but this does not show the potentially available
dietary P because true absorption coefficients decline with P intake. Wu et al.
(2000) use 85% as the maximum amount of digestible P, which is also used
here as the potentially available dietary P for microbial growth and passage to
the lower tract.

Urine
Milk
2
3
Bone and
soft
tissue
Indigestible P
Protozoal P
LI
indigestible P
SI
indigestible P
Bacterial P
Bile P
Microbial P
SI
digestible P
LI
digestible P
Digestible
P
Fig. 18.2. Schematic representation of the model of P metabolism in the ruminant. The
compartments were rumen (1), small intestine (2), large intestine (3) and extracellular fluid (4).
474 E. Kebreab and D.M.S.S. Vitti
were used in the model. High P concentrations occur in the rumen, ranging from
200 to 600 mg/l (Witt and Owens, 1983).
Bacteria are assumed to pass to the small intestine at a rate of 5.1% per
hour but protozoa, due to their larger size and ability to adhere to particles in
the rumen, pass at 45% of the rate of bacteria (Dijkstra, 1994). The ruminal P

where C
IP
is concentration of absorbable P in intestine (g/l). Maximum theor-
etical absorption through this process was 90 g/day and the parameters were
optimized by the model. Unabsorbed digestible P, which includes endogenous
P, is assumed to pass to the large intestinal digestible P pool at the same
fractional passage rate as for fluid. Endogenous faecal P is one of the most
important pathways responsible for almost 80% of P leaving the animal
(McCaskill, 1990). Undigested microbial P and indigestible dietary P in the
rumen are inputs to the indigestible P in small intestine and P from this pool
passes to the large intestine at a particulate matter passage rate of 4.0% per
hour.
The large intestine of sheep has the capacity to absorb significant quantities
of P (Milton and Ternouth, 1985), but this capacity does not appear to be used
due to the low concentration of ultrafiltrable P. Most of the P is present as
insoluble or nucleic acid (Poppi and Ternouth, 1979) in the large intestine.
Yano et al. (1991) concluded that in sheep, little absorption or secretion of P
appears to occur either in the rumen or large intestine. The potentially digest-
ible and indigestible P in large intestine are excreted in faeces at a fractional
passage rate of the large intestine (10.6%/h, Mills et al., 2001). Due to
selective retention of microbial matter within the caecum, microbial passage
rates were 85% of large intestinal digesta passage rate.
Mineral Metabolism 475
Inputs to the extracellular fluid pool are from P absorbed post-ruminally
and from bone resorption. The outputs are to the lower tract (via bile), bone
absorption, secretion in milk and excretion in urine. If a pregnant cow is
assumed, utilization by the pregnant uterus needs to be an output from this
pool. The volume of the pool was set at 20% of liveweight (Ternouth, 1968).
Digestible P in small intestine (microbial, dietary and salivary P) passed to the
small intestine, which is not excreted as ‘regulated P’ is assumed to have been

(Georgievskii, 1982). Normal levels for sheep are between 40 and 90 mg P/l
and values lower than 40 mg are indicative of deficiency (Underwood and
Suttle, 1999). There is a correlation between inorganic P in plasma and P
intake for animals fed deficient to moderate P levels (Ternouth and Sevilla,
1990; Scott et al., 1995). However, at high P intakes, inorganic P plasma
levels begin to stabilize. For sheep, levels of 27, 64 and 101 mg P/kg LW are
considered deficient, moderate and adequate, respectively (Braithwaite, 1985).
In cattle, P intake varying from 27.1 to 62.5 mg P/kg LW resulted in P plasma
levels of 47 and 77 mg/l, respectively. In contrast, some authors did not
observe a clear correlation between P intake and plasma levels (Louvandini
and Vitti, 1994; Louvandini, 1995).
Homoeostatic mechanisms in ruminants depend mainly on the reabsorp-
tion of P in the kidney and P secreted in saliva. A substantial amount of P
recycling takes place through saliva. The rate is influenced by the quantity and
physical form of the diet and by P intake (Scott et al., 1995).
Saliva normally contains 200–600 mg P/l but a variation of 50 to
1000 mg/l can occur (Thompson, 1978). The amount of P secreted in saliva
476 E. Kebreab and D.M.S.S. Vitti
has been reported to be directly related to blood inorganic P concentration.
Salivary P secretion was found to increase in direct relation to P intake and P
absorption (Challa and Braithwaite, 1988). Salivary P, because it is in inorganic
form, is easily available to rumen microbes. On average, salivary P inputs
represented 45–50% of the total P flow at the duodenum assuming no net
absorption of P from the rumen (Ternouth, 1997; Shah, 1999). It has been
reported that the salivary P secretion accounts for about 70% of total endogen-
ous P entering the alimentary tract of sheep (Annenkov, 1982) and represents
a major route of P excretion (Young et al., 1966).
P homoeostasis is normally maintained by control of absorption, excretion,
secretion into the gut and accretion in or resorption from bone. Homoeostasis
is simulated in the model by estimating key parameters that control movement

(Table 18.1).
Estimated P secretion in milk and unavailable P excretion in faeces are the
same in both models because the parameters were set as constants based on
milk yield and P intake, respectively. Although Wu et al. (2000) estimated
higher faecal P at higher P intakes, there was a general agreement in the
Mineral Metabolism 477
total faecal P excreted. The differences at higher intakes were possibly because
urinary P was underestimated by the predictions of Wu et al. (2000).
Experiments of Wu et al. (2000) and Morse et al. (1992) were used to
provide inputs for model simulation. Figure 18.3 shows that there was a close
agreement between model predictions and experimental results. Separate lines
for model predictions were required because the experiments had different DMI
and milk production, which modified the way the model predictions work.
The model can be extended to other ruminants by adjusting key param-
eters such as rumen and blood volume. There could be considerable intraspe-
cies differences in P metabolism, which could be influenced by a number of
factors. P interacts with other minerals, especially calcium, and responds to
levels of vitamin D and endocrine factors. These issues need to be addressed to
improve our understanding of P metabolism and better predict differences in P
responses within species.
We anticipate that the dynamic model will help to a better understanding of
P metabolism and lead to formulation of diets which will reduce environmental
pollution of P without compromising animal performance or health. This can
be done by matching the ruminant’s requirement for various physiological
Table 18.1. Comparison of model predictions for P in different pools with values reported by
Wu et al. (2000).
Faeces (g P per day)
Intake Saliva
a
Urine Mbl

c
MblMt, microbial and metabolic P output to faeces (g/day).
d
UnAv, unavailable dietary P (g/day).
e
Reg, regulated P (g/day).
f
ND, not determined.
478 E. Kebreab and D.M.S.S. Vitti
processes with dietary P intake, which can be simulated using the dynamic
model.
Copper
Copper (Cu) is an essential trace element required for enzyme systems, iron
metabolism, connective tissue metabolism and mobilization, plus integrity of
the central nervous and immune systems. The essentiality of Cu in ruminants
had long been established when evidence was found that Cu is required for
growth and prevention of disease (McDowell, 1992). Copper has also been
reported to affect lipid metabolism in high-producing dairy cows and beef cattle
(Engle et al., 2000, 2001). In many parts of the world, Cu deficiency has been
identified as a serious problem for grazing ruminants under a wide range of soil
and climatic conditions (Ammerman et al., 1995).
Copper requirements and absorption
Dietary Cu requirements vary greatly among species. Dairy cattle can toler-
ate higher dietary levels of Cu than can safely be fed to sheep. Copper
Phosphorus intake (g/day)
0 50 60 70 80 90 100 110 120
Faecal phosphorus excretion (g/day)
0
30
40

complex chemicals and limit absorption in the gastrointestinal tract. The ab-
sorbability of Cu also depends on the sources of Cu for ruminants. In silages,
Mo has a small and little studied effect on absorbability. Absorbable Cu (A,%)in
ruminants fed fresh grass was described by the equation:
A ¼ 5:7 À 1:3S À 2:785ln (Mo) þ 0:227(Mo  S) (18:3)
where Mo is given in mg/kg DM and S in g/kg DM (Underwood and Suttle,
1999).
Modelling copper metabolism
Quantitative descriptions of Cu metabolism available in the literature are largely
dependent on empirical modelling and limited mechanistic modelling based on
kinetic studies. The main kinetic models were those of Weber et al. (1980,
1983) using
64
Cu in sheep, Gooneratne et al. (1989) using
67
Cu in sheep, and
Buckley (1991) using the stable isotope
65
Cu in lactating dairy cows. Symonds
and Forbes (1993) developed a framework of a mechanistic model of the
possible routes of movements of Cu in the ruminant body based on kinetic
models of Cu metabolism in sheep (Weber et al., 1980; Gooneratne et al.,
1989) (Fig. 18.4). The boxes in Fig. 18.4 represent pool sizes and input,
output and between-pool fluxes can be estimated from balance trials or injec-
tion of radioactive markers and sampling of tissues over time.
Homoeostasis of Cu in ruminants is achieved predominantly by hepatic
storage and biliary secretion (Underwood and Suttle, 1999). Copper metabol-
ism in the liver has been represented by more than one compartment based on
the information available to resolve Cu mobility and the species under study.
480 E. Kebreab and D.M.S.S. Vitti

endogenous)
Dietary
copper
Absorbed
Endogenous
loss
(i)
Liver
A
Liver
B
Liver
C
Blood
Tissue
Kidney
Urine
Fig. 18.4. Diagram of the possible routes of movement of copper in the ruminant body.
A represents a temporary storage compartment for copper in the liver destined for exchange
with blood and excretion into bile (ii), B represents a temporary storage for incorporation into
caeruloplasmin and C represents a long-term storage compartment from which excretion into
bile (iii) and secretion into blood are thought to be operative following tetrathiomolybdate
administration. Excretion into bile was from the blood (i), temporary (ii) and long-term
(iii) Cu storage compartments in the liver (Symonds and Forbes, 1993).
Mineral Metabolism 481
requirements, absorption, sources of Cu and effect of Cu on lipid metabolism.
Therefore, in this chapter, only a limited update of quantitative aspects of Cu
metabolism has been possible.
Conclusions
In this chapter, a similar approach was adopted to that taken by Symonds and

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The Whole Animal
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19
Growth
G.K. Murdoch,
1
E.K. Okine,
1
W.T. Dixon,
1
J.D. Nkrumah,
1
J.A. Basarab
2
and R.J. Christopherson
1
1
Department of Agricultural, Food and Nutritional Science, University of
Alberta, Edmonton, Alberta T6G 2P5, Canada;
2
Western Forage/Beef Group,
Lacombe Research Centre, 6000 C&E Trail, Lacombe, Alberta T4L 1W1,
Canada
Introduction
Growth of the whole animal involves an increase in mass as a result of changes
in the size, development and structure of its various organs and tissues. Growth
involves increases in both cell numbers (hyperplasia) and cell size (hypertrophy),
and includes the deposition of substantial amounts of extracellular matrix
material (e.g. collagen and mineral) in cartilage and bone, extracellular fluids
and electrolytes and accumulation of structural or energy storage molecules

(GHRH) and negatively regulated by inhibitory feedback of GH itself and
insulin-like growth factor I (IGF-I) on GHRH-producing cells in the hypothal-
amus, as well as somatostatin (SS), which inhibits the release of GH (Veldhuis
et al., 1991). GH acts as a systemic anabolic hormone on tissues expressing its
specific receptor such as epiphyseal growth plates, skeletal and cardiac muscle,
placenta, liver, kidney, brain and cartilage but is catabolic in function on
adipose tissue. Somatic growth in vertebrates is dependent on growth hor-
mone, and insufficiency or insensitivity results in dwarfism (Jorgensen, 1991)
while hypersecretion induces gigantism, acromegaly and insulin insensitivity
accompanied by hyperglycaemia. Of extreme importance to livestock produc-
tion is the fact that normal, and slightly elevated, serum GH promotes depos-
ition of lean body mass with associated reduction of adiposity.
GH binds to GH receptor as a homodimer and initiates signal transduction
mechanisms affecting metabolism and growth (Breier, 1995). Activation of GH
receptor in the liver induces an increase in production of IGF-I, which mediates
many of the anabolic effects (Thiessen et al., 1994). Growth hormone is also
involved in modulating other processes such as lipid, nitrogen, mineral and
carbohydrate metabolism (e.g. Luft et al., 1958).
In adipose tissue, GH decreases lipogenesis, increases lipolysis and fatty
acid mobilization and oxidation, and inhibits insulin-mediated lipogenesis, prob-
ably by direct action on GH receptors (O’Connor et al., 1999). Other roles of
GH include elevation of plasma glucose levels and decreased glucose oxidation,
mainly through insulin antagonism (Campbell et al., 1985; Wurzburger et al.,
1993). Treatment of ruminant livestock with growth hormone results in in-
creased average daily gain (ADG) and feed efficiency, decreased fat accretion
and increased protein accretion (e.g. Hayden et al., 1993). Gladysz et al.
(2001) reported that mean concentrations and amplitudes of GH in blood
plasma of sheep were higher in feed-restricted compared to control animals,
possibly due to reduced somatostatin release. The increase in circulating GH
with feed restriction serves to mobilize lipid and glycogen stores for immediate

230
250
270
290
310
Body weight (kg)
1.2−2.2ϫM
2.2−1.2ϫM
1.2−2.2ϫM
2.2−1.2ϫM
(b) Concentrate
Fig. 19.1. Examples of compensatory growth in beef steers as they are switched, at 6 weeks,
either from a restricted level (1.2 Â maintenance) to a higher (2.2 Â maintenance) level of feeding
or vice versa. Data are presented for animals fed either high roughage (a) or high concentrate diets
(b). (G.K. Murdoch et al., unpublished observations.)
Growth 491
suggests that there may be a threshold effect in terms of degree of nutrient
restriction, and/or involvement of other endocrine processes.
Insulin-like growth factors and IGF-binding proteins
Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) are part of a
family of polypeptides structurally related to proinsulin and which are synthe-
sized by the liver in response to GH stimulus (Thiessen et al., 1994). IGF-I acts
in an autocrine and/or paracrine manner (Louveau et al., 2000) to influence
growth. After release, IGFs bind mainly to IGFBPs, but also other plasma
proteins, which serve to stabilize and increase the half-life of circulating IGF,
and also modulate delivery of IGF to target tissues. For example, in sheep, the
half-life of IGF-I in plasma increased from 10 min in the free form to 545 min
when it was bound to IGFBP-3 (Gatford et al., 1997). Thus IGFBP-3 has been
suggested as the major carrier of IGF-I in adult sheep plasma whilst in the fetal
sheep IGFBP-3, IGFBP-2 and a soluble form of the IGF-II receptor each appear

492 G.K. Murdoch et al.
a complex interaction between the growth hormone system and other path-
ways in the regulation of growth and energy homoeostasis in animals.
Insulin
The main function of insulin is the promotion of nutrient storage. It plays a
major role in lipogenesis, liver and muscle glycogenesis and protein synthesis
(Davis et al., 1998). In the liver, insulin regulates Glut-4 mediated hepatic
glucose uptake and is also essential for the production of IGFs. Peripheral
administration of insulin inhibits lipolysis, and it opposes the action of GH in
fat cells (Woods et al., 1998). Fasting in heifers causes parallel reductions in
circulating insulin and leptin levels (Amstalden et al., 2000), the flip side of the
fact that both are upregulated by elevated plasma nutrient levels, especially
glucose for insulin and free fatty acids for leptin. Heat production in sheep is
also positively related to plasma insulin concentration (Table 19.1), probably as
a result of anabolic responses to the hormone.
Leptin
Leptin, a 146-amino acid peptide is expressed primarily in adipose tissues
(Zhang et al., 1994). Leptin crosses the blood–brain barrier through a saturable
specific transport mechanism involving two short isoforms of its receptor, Ob-
Ra and Ob-Re (Heska and Jones, 2001). Inside the central nervous system,
leptin binds to cells expressing the leptin receptor in the arcuate, ventromedial,
paraventricular and dorsomedial hypothalamus (Tartaglia et al., 1995). It
serves as an indicator of energy status especially adipose stores and is a
postprandial satiety signaller (Houseknecht et al., 1998). Leptin receptors
(long form; Ob-Rb) are single transmembrane proteins belonging to the
Table 19.1. Relationship between heat production and the density of beta-adrenergic
receptors (fmol/mg protein) in different tissues of sheep. Data from Ekpe and Christopherson
(2000) and Ekpe et al. (2000a,b).
Independent variable Intercept Regression coefficient r-value Probability
Heart BAR density 2.12 0.008 0.55 0.01