Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

Подождите немного. Документ загружается.

good fungicide for control of downy mildews.

This class of fungicide (strobilurins) was derived

from the study of edible woodland mushrooms.

10.

0043 Inhibition of fungal biosynthesis of nucleic acids.

Some hydroxypyrimidines, e.g., ethirimol, were

developed during the 1960s and are thought to

inhibit fungal biosynthesis by inhibiting adeno-

sine deaminase in the purine reutilization path-

way. They have systemic action and are protectant

and eradicant.

11.

0044 Inhibition of mitochondrial electron transport.

Cytochrome bc

is involved as the fungicide in-

hibits electron transport in oxidative phosphoryl-

ation in the fungal mitochondria and energy

production. Several aryl carboxanilides (oxazoli-

dinones) inhibit succinate ubiquinone reductase

and hence fungal respiration. This group of

fungicides are specifically effective on Basidio-

mycetes. They are systemic, protectant, and re-

sidual. Carboxin is an older example of this class

while famoxadone has much more recently

reached the market.

12.

0045 Inhibition of glycerophospholipid biosynthesis.

Edifenphos and validamycin A have this mode

of action. Edifenphos is used as a protectant and

eradicant fungicide for the control of rice blast.

13.

0046 Inhibition of protein synthesis. Some fungicides

of microbial origin are used commercially to

control disease, e.g., blasticidin S by foliar appli-

cation to control rice blast, and jinggangmycin to

control sheath blight of rice. Since these ‘bio-

chemicals’ are made biologically, they may well

be specific for target organisms. They are also

likely to degrade in vivo and so be safer than

synthetic chemicals.

14.

0047 Acquired systemic resistance in the plant and

increase in the effectiveness of its defense mech-

anism. Some chemicals act not by killing the

fungal disease but by affecting the defense mech-

anisms in the metabolism of the plant so that

it is more resistant to attack and so continues to

develop and function normally; endogenous

salicylic acid is believed to play a crucial role in

the induction process. Probenazole is a systemic

compound used to control rice blast and can be

absorbed by the roots. Some antifungal proteins

have been found to increase the defense mechan-

ism of the plant, although these have yet to

impinge on the commercial market.

15.

0048 Biological control using bacteria, virus, and other

fungi can work, although its commercial exploit-

ation to date has not been successful. However,

this approach can be a useful tool in integrated

pesticide management (IPM) – and has been op-

erative in natural systems for millions of years!

16.

0049Unknown or very uncertain mechanism of action.

Certain organophosphorus compounds have

been widely used for particular crops for some

time without any definitive understanding of

their mode of action, although they are now

believed to interfere with fungal choline bio-

synthesis. Pyrazophos is used as a protectant

and eradicant fungicide for the control of rice

blast. Tolclofos-methyl is a nonsystemic com-

pound of a different type used, for example,

on vegetables and fruits.

Aromatic hydrocarbons. Quintozene can be

used in dressing seed. Chlorothalonil has a

nonsystemic and protective action, giving

good control of Oomycetes. This group of

fungicides has become increasingly suspect

toxicologically, e.g., chlorothalonil is now

banned in some countries.

005

Pencyuron is also nonsystemic and protectant

and controls rice sheath blight.

Dicloran is protectant for control of Botrytis,

Sclerotonia, and Monilinia spp. in fruits.

005

Cymoxanil, a cyanoacetamide, is protectant

and curative in action and is usually used in

combination with compounds having contact

or local systemic activity.

Resistance

0055Problems can arise from the build-up of resistance of

fungi to control by a fungicide or, more often, by a

group of fungicides.

0056Before 1970, resistance to the effects of the multi-

site inhibitor fungicides then mostly used was infre-

quent and only occurred after prolonged use, e.g., in

vineyards. Where resistance did occur it was probably

nonspecific in nature, e.g., from reduced uptake on

the foliage surface.

0057With the introduction of site-specific systemic fun-

gicides, the incidence of resistance problems became

much more frequent and problems emerged more

quickly. The risk of resistance from site-specific fun-

gicides may have been increased through selection

pressure resulting from their greater effectiveness

and eradicant action.

0058To resolve a resistance problem, a systemic chem-

ical may have to be formulated alongside another

active ingredient of a different type, such as a dithio-

carbamate, because of a partial loss of effectiveness in

controlling fungal infections. Resistance problems

with sterol biosynthesis inhibitors can sometimes be

overcome by switching to another sterol biosynthesis

inhibitor with a low level of cross-resistance or by

changing the application method. Growers will also

look to plant breeders for cultivars of plant, fruit, or

vegetable that are more resistant to attack by disease.

2838 FUNGICIDES

0059 The Groupement International des Associations

Nationales de Fabricants de Produits Agrochemiques

(GIFAP) has a Fungicides Resistance Action Commit-

tee (FRAC) which has working groups covering the

six main classes of fungicide for which resistance is a

problem: sterol biosynthesis inhibitors, phenylamides,

dicarboximides, benzimidazoles, anilinopyrimidines,

and strobilurins. Information and recommendations

on fungicide resistance are available from this source.

0060 A serious resistance problem has occurred with the

control of late blight in potatoes. Aggressive popula-

tions of the A2 mating type of Phytophthora infestans

have developed so that severe losses have occurred.

Strategies that have been developed to cope with

the problem include using nonsystemic protectant

fungicides, translaminar fungicides, and a single

R-enantiomer formulation of metalaxyl. Resistance

to the systemic fungicides normally used has been

marked and these failed to control the situation

effectively.

0061 Only a limited number of field trials with genetic-

ally modified plants have involved resistance to fungi.

0062 Effective fungicide resistance management is cru-

cial. Much management is based on experience but

there is a need to develop predictive tools based on

mechanistic and other knowledge and data. Many

countries have national programs to monitor fungi-

cide resistance.

Extent of Use

0063 The Food and Agriculture Organization gives the

world trade in fungicides in 2000 to be worth nearly

US$ 3 billion (about 20% of the total pesticide

market). This is probably an underestimate of the

amounts actually used. The proportion of total fungi-

cide sales, as an estimate of use, by region worldwide

in 1995 is indicated in Table 3. In the same study, the

total sales of fungicides among various crops world-

wide were assessed, as shown in Table 4.

0064 Table 5 shows the sales of fungicides on vegetables

and cereals by region worldwide. It should be noted

that all global figures for pesticide sales/use are

approximate as reliable data may not be obtainable

from China or some other South-east Asian countries.

Seed treatments are estimated to account for about

10% of the total fungicide market. Although an in-

creasing awareness of the advantages of IPM is evi-

dent, use of fungicides globally continues to increase.

0065Fungicides are available for home garden use on

soft fruit, legumes, and other vegetables as well as on

ornamentals.

Methods of Application

0066Fungicides are applied to growing crops in a wide

variety of ways. The active ingredient(s) may be formu-

lated with added wetter, emulsifier, filler, etc. as an

emulsifiable concentrate, a suspension concentrate, a

fungicidal dust, as granules, or as a wettable powder.

Microencapsulated systems are now widely used and

have advantages such as reduction in operating

hazards, controlled release, and protection of the active

chemicals against degradation in the field. Microemul-

sions are now being developed and offer an advantage

of being thermodynamically stable. Reference should

be made to the article on pesticide types for detailed

information on techniques of application.

0067Applications to harvested produce are closely linked

with procedures for storage and marketing the par-

ticular commodity. For example, dipping citrus fruit

in a solution of an appropriate fungicide may be

tbl0003 Table 3 Fungicide sales by region in 1995

Region Percentage of total worldwide

fungicide sales

Western Europe 41

East Asia 35

North America 10

Latin America 8

Eastern Europe 3

Rest of the world 3

Calculated from data from County NatWest WoodMac for 1995.

tbl0004Table 4 Relative sales of fungicides for various crops

worldwide in 1995

Crop Percentage of total sales

of fungicides

Fruits and vegetables 41

Cereals 25

Rice 15

Maize 2

Cotton 2

Soybeans 1

Sugar beet 1

Potato 4

Others 9

Calculated from data from County NatWest WoodMac for 1995.

tbl0005Table 5 Relative sales of fungicides for use on vegetables and

cereals worldwide in 1995

Region Percentage of world sales for use on

Fruitsand vegetables Cereals

Western Europe 35 83

East Asia 39 6

North America 15 4

Latin America 8 3

Eastern Europe 1 2

Rest of the world 2 1

Calculated from data from Country NatWest WoodMac for 1995.

FUNGICIDES 2839

followed by wrapping the individual fruits in

fungicide-impregnated paper before packing in trays

or boxes for transport.

0068 To control some diseases, the seed is treated before

planting by dressing with a dust or liquid or by

encapsulating the seed with a nutrient coat which in-

cludes fungicide, e.g., sugar beet is normally sown in

this way. Fungicidal seed bed drenches are also used.

0069 Surface biocides are applied to empty animal

houses and buildings for control of fungal and

bacterial infection.

0070 Significant developments in product packaging and

pesticide delivery systems have taken place in recent

years. Successful development of refillable containers

of all sizes, water-dissolvable films or gel tablets, and

microencapsulated pesticides substantially reduce or

eliminate the need for recycling or disposal of pack-

aging that has been exposed to pesticide and hence

potentially may leave hazardous residues.

Examples of Benefits in using Fungicides

1.0071 The quantity, or yield, of the crop or foodstuff is

increased, making marketing more commercially

viable. Globally, potential losses in crops because

of disease are estimated to be about 17% and these

are reduced by about a quarter to about 13% by

using fungicides. (This averages out the effects of

epidemics in which entire crops are lost.) Table 6

shows some of the global advantages of using

fungicides in growing rice.

00720072 Work carried out in Germany on the wheat

harvests in 1991–93 indicated that the average

yield would drop from 6.4 t ha

1

to 4.2 t ha

1

without the use of fungicides. Furthermore, in a

no-pesticide scenario (no herbicides or insecticides

either) the loss rate for diseases would increase

from 6% to 11%.

00730073 Infestation is related to air temperature and

humidity and modern methods can forecast when

a fungal infection is likely so that growers can

apply fungicides to control proliferation of spores.

Forecasting rapid spread of disease and advising

on the timing for fungicide treatment was

pioneered for the control of potato blight.

0074The quantity of the commodity is increased to

obtain a wider market and a better value. Without

fungicide dips with citrus fruit for export and of

impregnated packing for transport, infections

latent from the preharvest environment would se-

verely reduce the proportion of a consignment that

would be marketable and lower financial returns

markedly. People prefer to buy apples without

unsightly apple scab lesions in the skin and will

refuse to buy inferior produce.

0075A disease may be eliminated. Bunt or stinking smut

(Tilletia caries) of wheat now rarely occurs in the

UK. It is probable that such diseases have been very

efficiently controlled rather than eradicated.

Financial considerations of these benefits have to

offset the cost of buying and applying fungicides.

Safety Implications and Toxicology

0076Before a fungicide can be marketed, the manufacturer

submits information on the biological, chemical, and

physical properties of the active ingredient and of its

formulations to pesticide registration authorities of

the countries concerned. Possible effects on the oper-

ator, the consumer and on the environment are care-

fully evaluated and registration authorities have to be

completely satisfied of the safety of the proposed

chemical, its formulations, and the labeling directions

for its use, as well as of safety arrangements in trans-

port and storage.

0077Where sufficient information is available, the Joint

FAO/World Health Organization (WHO) Meeting on

Pesticide Residues (JMPR) has estimated acceptable

daily intakes (ADIs) for pesticides. They are ex-

pressed in milligrams of the chemical per kilogram

of body weight. Table 7 gives ADIs for some common

fungicides.

0078Nevertheless, some adverse effects on wildlife and

the environment have been attributed to fungicides.

For example, investigations have suggested that ipro-

dione has altered bird behavior, reduced egg produc-

tion, reduced hatching rate, and impaired mysid

reproduction. Azole fungicides, however, are known

to have a low persistence in the environment and a

low acute toxicity to birds. Triorganotin compounds

are, expecially toxic to aquatic life.

0079Some fungicides once widely marketed are now

withdrawn on toxicological grounds and their

movement in trade between countries required prior

informed consent (PIC). Organomercury compounds

and hexachlorobenzene (HCB) are essentially banned

tbl0006 Table 6 Potential losses and actual losses to diseases in rice

in 1991–93, by region

Region Potentialloss

from diseases

(% of yield)

Actualloss

to diseases

(% of yield)

Western and southern

Europe

21 9

North America and Oceania 24 8

East Asia 22 12

Rest of the world 18 17

These estimates are made alongside estimates of losses to other pests.

Based on data from Oerke E-O at the 12th International Symposium on

Modern Fungicides and Antifungal Compounds.

2840 FUNGICIDES

internationally, having a high toxicological risk to

humans. Dinoseb and binapacryl are also suspect on

toxicological grounds.

Maximum Residue Limits (MRLs)

0080 The Codex Committee on Pesticide Residues (CCPR)

recommends, on the advice of the JMPR, maximum

residue limits for pesticides in foodstuffs, whether

they are derived from preharvest or postharvest use,

where such limits are necessary and whether suffi-

cient information is available. MRLs generally apply

to the raw commodity, although (separate) MRLs can

be established for foods that have been processed,

fabricated, or manufactured, if necessary. Codex

MRLs for fungicides are listed in Table 8.

0081 Maximum levels have also been fixed for residues

of some fungicides by the European Community and

the values corresponding to those of the Codex,

where they occur, are given in Table 9. It will be

seen that the European limits do not exactly corres-

pond with those of the Codex, although they are

generally of the same order of magnitude. This is

because the different limits were the result of evalu-

ations at different times, based on different data and

by different experts. Some countries also have limits

of their own covering particular interests. The overall

lack of convergence of pesticide residues limits in

foods is less than satisfactory.

Analysis of Residues

Methods

0082A necessary precursor to determining any fungicides

in a sample of a food is a satisfactory, and in as far as

is possible representative, method of sampling.

Both the CCPR and the European Community have

recently addressed this issue and have revised their

recommendations. Many fungicides are one of a

small group of compounds having similar chemical

structures and/or physical properties. A group, or

groups, can often be analyzed using a ‘multiresidue’

method rather than by employing individual proced-

ures for each possible fungicide.

0083If present, residues can be identified and quantified

using a range of gas chromatographic (GC) columns

and detectors, especially mass spectrometric detectors

for enforcement purposes. Fungicides not amenable

to GC are often determined using high-performance

liquid chromatography with ultraviolet or fluores-

cence detectors. Dithiocarbamates are usually deter-

mined as carbon disulfide by a GC head-space

procedure. Some fungicides, e.g., chlorothalonil, are

tbl0007 Table 7 Acceptable daily intakes (ADIs) of some fungicides

used in agriculture and food storage

Fungicide ADI (mg kg

1

bodyweight)

Bitertanol 0.01

Carbendazim 0.03

Chlorothalonil 0.03

Dichlofluanid 0.3

Fenarimol 0.01

Imazalil 0.03

Iprodione 0.06

Metalaxyl 0.03

Propiconazole 0.04

Thiabendazole 0.1

Tolclofos-methyl 0.07

Triadimenol 0.05

Data from Codex Alimentarius vol. 28, 2nd edn. Pesticide Residues in Food ^

Maximum Residue Limits. Joint FAO/WHO Food Standards Programme.

Rome: Food and Agriculture Organization (1998).

tbl0008 Table 8 Codex maximum residue limits (MRLs) for some fungicides used in agriculture and food storage

Fungicide Codex MRL (mg kg

1

)in

Apple and pear Banana Cabbage Citrus fruits Grapes Potato Peach Tomato Wheat

Bitertanol 2 0.5 1 0.1

Carbendazim 1 3

Chlorothalonil 0.2 1 5 0.5 0.2 (1) 5 0.1

Dichlofluanid 5 15 0.1 5 2 0.1

Fenarimol (0.3) 0.2 (0.3) (0.5)

Imazalil 5 2 5 5 0.01

Iprodione 5 10 10 5

Metalaxyl 1 0.5 5 1 0.05

0.5

Propiconazole 0.1 0.5 1 0.05

Tolclofos-methyl 0.2

Thiabendazole 10 3 10 5 2

Triadimenol 0.5 0.2 2 0.5 0.2

Data from Codex Alimentarius vol. 28, 2nd edn. Pesticide Residues in Food ^ Maximum Residue Limits. Joint FAO/WHO Food Standards Programme. Rome:

Food and Agriculture Organization (1998).

At or about the limit of determination.

MRLs in parentheses are not yet finalized Codex standards.

FUNGICIDES 2841

difficult to analyze accurately as they are unstable

and degrade during analysis. Sensitive immunoassay

techniques have been developed for determining a

number of fungicides: benomyl, chlorothalonil, fen-

propimorph, metalaxyl, triadimefon, and other com-

pounds. Such approaches have not, as yet, superseded

the instrumental chemical approaches for definitive

work, although they are increasingly useful for

screening purposes.

Monitoring Data

008 4 It is not possible to summarize adequately all the

selective monitoring data for fungicide residues in

foodstuffs in those countries that report their work

in the scientific or official publications. However, it

appears that of the order of 1% of retail samples may

contain residues above a residue limit. In an EU

survey of 9700 samples, dithiocarbamates and benzi-

midazoles were the fungicides occurring most often as

residues in foods and exceeded maximum limits the

most frequently.

0085 The relatively low toxicity, together with the small

amounts, of copper and sulfur formulations likely to

be in foods renders residue analysis for these moieties

unnecessary. Significant traces of fungicides used

for seed dressing, seed bed drenching, or as surface

biocides in buildings are unlikely to be found in

foodstuffs at market.

Seealso: Citrus Fruits:Compositionand

Characterization; Pesticides and Herbicides:Typesof

Pesticide; Sugar:Sugarbeet

Further Reading

Copping LG and Hewitt HG (1998) Chemistry and Mode

of Action of Crop Protective Agents. London: Royal

Society of Chemistry.

Dehne H-W and Derke E-C (1998) Impact of diseases and

disease control on crop production. In: Hutson D and

Miyamoto J (eds) Fungicidal Activity, pp. 1–21. Chi-

chester: Wiley.

European Union (1998) Directive 98/82/EC of 27 October

1998 amending Council Directive 91/414/EEC concern-

ing the placing of protection products on the market.

Official Journal of the European Communities L 290/

25–54.

European Union websites (2002) http://europa.eu.int/

comm/dgs/health_consumer/index_en.htm and http://

europa.eu.int/comm/foods/fs/ph_ps/index_en.htm/

FAO (1998) Joint FAO/WHO Food Standards Programme.

Codex Alimentarius, vol. 28, 2nd edn. Pesticide Resi-

dues in Food – Maximum Residues Limits. Rome: Food

and Agriculture Organization.

FAO (2002) Statistical databases, pesticide trade field.

Available at www.fao.org.

Hewitt HG (1998) Fungicides in Crop Protection, 221 pp.

Wallingford, UK: CAB International.

Kendall SJ and Hollomon DW (1998) Fungicide resistance.

In: Hutson D and Miyamoto J (eds) Fungicidal Activity,

pp. 87–108. Chichester: Wiley.

Kurihara N and Miyamoto J (eds) (1998) Chirality in Agro-

chemicals. Chichester: Wiley.

Lyr H (1987) Modern Selective Fungicides. Harlow, UK:

Longman.

Lyr H, Russell PE, Dehne H-W and Sisler HD (1999)

Modern Fungicides and Antifungal Compounds II.

12th International Reinhardsbrunn Symposium. And-

over, UK: Intercept.

Oerke E-C (1996) Impact of diseases and disease control

on crop production. In: Lyr H, Russell PE and Sisler HD

(eds) Modern Fungicides and Antifungal Compounds,

pp. 17–24. Andover, UK: Intercept.

Ordish G (1967) In: Torgeson DC (ed.) Fungicides. An

Advanced Treatise, vol. 1, pp. 39–62. New York:

Academic Press.

Pesticides 2002. London: HMSO.

Roberts TR, Hutson DH, Jewess PJ, Lee PW, Nicholls PH

and Flimmer JR (eds) (1999) Metabolic Pathways of

Agrochemicals. Part 2: Insecticides and Fungicides.

London: Royal Society of Chemistry.

Russell P (1999) Fungicide resistance management: into the

next millennium. Pesticide Outlook 10(5): 213–215.

tbl0009 Table 9 European Union (EU) maximum limits for some fungicides used in agriculture and food storage

Fungicide European Community maximum limits (mg kg

1

)in

Apple and pear Banana Cabbage Citrus fruits Grapes Peach Potato Tomato Wheat

Carbendazim 2 1 5 2 1 3

0.5 0.1

Chlorothalonil 1 0.2 3 0.01

1, 3 1 0.01

2 0.1

Fenarimol 0.3 0.3 0.02

0.3 0.02

0.02

Imazalil 5 2 0.02

5 0.02

0.02

, 5 0.5 0.02

Iprodione 10 3 5 0.02

, 2, 5 10 5 0.02

5 0.5

Metalaxyl 1 1 0.05

1, 2 0.05

0.05

Propiconazole 0.05

0.05

0.5 0.2 0.05

0.05

Thiabendazole 5 3 0.05

6 0.05

0.05

, 5 0.05

0.05

The EU has not as yet fixed maximum levels in foodstuffs for many of the fungicides discussed in this chapter.

Where two figures are entered, these are values for different commercial commodities, e.g., table grapes, wine grapes.

Lower limit of analytical determination.

2842 FUNGICIDES

GALACTOSE

C A Williams, Kingswood, Wotton-under-Edge, UK

This article is reproduced from Encyclopaedia of Food Science,

Occurrence

0001 Galactose is a monosaccharide and has the same

chemical formula as glucose, i.e., C

.Itis

similar to glucose in its structure, differing only in

the position of one hydroxyl group. This difference,

however, gives galactose different chemical and

biochemical properties to glucose.

0002 The major dietary source of galactose is lactose, a

disaccharide formed from one molecule of glucose

plus one of galactose. Lactose is found only in milk;

after weaning, significant quantities of dietary lactose

are found only in dairy products (Table 1). Lactose

levels are lower than expected in some dairy products,

where it has been used by the microbes involved in

processing the food.

0003 Lactose, a byproduct of the dairy industry, can be

hydrolyzed to produce lactose hydrolysate syrup,

which contains lactose, galactose, and glucose. This

syrup is used as a sweetener in biscuits, confectionery,

and some dairy desserts. Thus, small amounts of

lactose and galactose can appear in nondairy foods.

(See Lactose.)

0004 Apart from its presence in lactose hydrolysate

syrup, the monosaccharide galactose is seldom

found in the diet, although it has been identified as a

trace component of some seeds and pulses.

Absorption

0005 It has been established that the monosaccharides

are absorbed at different rates from the small

intestine. Initial studies, using animal models, showed

that glucose and galactose are absorbed at a much

faster rate than the other monosaccharides, and

galactose is absorbed at a slightly faster rate than

glucose. This finding has been confirmed in humans.

(See Glucose: Function and Metabolism.)

0006 In the brush border of the small intestine, there is

a carrier that is shared by glucose and galactose;

interaction between the carrier and an adjacent

sodium pump allows the monosaccharides to be

actively accumulated in the intestinal cell prior to

their removal into the circulation.

0007Galactose absorption is an active process in that it

requires energy (in the form of adenosine triphos-

phate, or ATP) and it can be stopped by the presence

of metabolic inhibitors. The common carrier system

concept is supported by knowledge of a rare clinical

condition of glucose–galactose malabsorption, in

which neither monosaccharide can be absorbed

efficiently because of the absence or impairment of

the common carrier.

0008Prior to absorption, galactose has to be released

from lactose. This occurs in the presence of lactase,

a disaccharidase, found in the brush border of the

mucosal epithelial cells of the small intestine.

0009Human lactase has a pH optimum of 5.5–6.0, and

its highest levels of activity are found in the jejunum,

with lower levels occurring in the duodenum and

ileum. It is thought that the enzymes that hydrolyze

sucrose and maltose are closely aligned with their

monosaccharide carriers. This may not be so for lac-

tase. However, in reality, the rate of lactose hydrolysis

does not appear to limit the quantity of galactose or

glucose absorbed from lactose.

0010Lactose intolerance occurs when the mucosal cells

do not produce sufficient quantities of lactase to

hydrolyze ingested lactose. As a result of this

insufficiency, undigested lactose remains in the small

intestine and, because of its osmotic potential, draws

water into the intestinal lumen. On arrival at the large

intestine, the lactose can then be fermented by the

microflora present to produce various gases and

acids. The symptoms produced can range from a

mildly bloated feeling to watery, explosive diarrhea.

There are three kinds of lactose intolerance:

0011Congenital lactase deficiency is an extremely rare

disorder in which lactase is absent from birth. As

lactose is a major constituent of the neonatal diet,

early diagnosis and instigation of a lactose-free

diet are essential if the condition is not to be fatal.

0012Secondary lactase deficiency occurs as a result of

damage to the intestinal mucosa, caused, for

example, by an infection or disease. Lactase levels

return to normal on successful treatment of the

primary disorder.

0013 In primary lactase deficiency, lactase levels are

normal at birth but have declined by adulthood. A

fall of lactase levels by adulthood has been noted in

other mammals, but it was in the early 1960s that

the condition was described in humans. Subse-

quently, it has been found that primary lactase defi-

ciency is the normal state in most races, and with

few exceptions, it is only in white Caucasians that

lactase levels remain high in adulthood. Most lac-

tose-intolerant individuals do not abstain totally

from milk and can take small quantities regularly,

but large quantities of milk are to be avoided. The

absorption of other nutrients is not affected by

drinking small quantities of milk. (See Food Intoler-

ance: Lactose Intolerance.)

Metabolism of Galactose

0014 The main route of galactose metabolism – the Leloir

pathway – results in its conversion to glucose

1-phosphate, which can enter the glycolytic pathway

(Figure 1). Intermediates of this pathway be used in

glycogenesis, or mucopolysaccharide and glycoprotein

synthesis. The pathway exists in the cytoplasm of the

cells and is most active in the liver.

0015 The Isselbacher pathway exists as an alternative

route for metabolism of galactose 1-phosphate

(Figure 1), a potentially toxic metabolite of galactose.

0016 Pathways exist for the reduction of galactose to

galactitol and for dehydrogenation to galacturonic

acid.

0017 There are two forms of clinical galactosemia, in

which an enzyme concerned with galactose metabol-

ism is absent from birth. Classical galactosemia is the

result of a deficiency of galactose-1-uridyltransferase,

so that galactose is phosphorylated to galactose

1-phosphate (gal 1-p) and no further. If the condition

remains unchecked, gal 1-p and galactose accumulate

in the tissues and can result in liver malfunction,

cataract, mental retardation and failure to thrive.

Early diagnosis and initiation of a galactose-free

diet are essential. The second type of clinical galacto-

semia is galactokinase-deficient galactosemia, and

this results in the accumulation of unphosphorylated

galactose in the tissues. It is characterized by the

development of cataracts in the first or second decade

of life. Cataracts in both types of condition are caused

by an accumulation of galactitol in the lens of the eye.

Metabolic Response to Galactose

0018The liver is the major site of galactose uptake and

metabolism in humans, and practically all circulating

galactose is removed by the liver. At one time, the

disappearance of galactose from blood following an

oral load was used as a test of liver function.

0019Normally, serum galactose levels are negligible in

a healthy fasting individual. It is only after ingestion

of galactose or lactose that they increase. The change

Galactose

Galactose 1-phosphate

Glucose 1-phosphate

ATP

UTP

UDP-glc

glc 1-p

UDP-galactose

UDP-glucose

ADP

fig0001Figure 1 Galactose metabolism – the major pathways. The

Leloir pathway: 1, galactokinase; 2, galactokinase 1-phosphate

uridyl transferase; 3, UDP-galactose 4-epimerase; 4, UDP-glu-

cose pyrophosphate. The Isselbacher pathway: 5, UDP-galactose

pyrophosphorylase. Note: although unidirectional arrows have

been drawn, most reactions are reversible. ATP, adenosine

triphosphate; ADP, adenosine diphosphate; UTP, uridine triphos-

phate; UDP, uridine diphosphate; glc, glucose; glc 1-p, glucose

1-phosphate; PP

, inorganic diphosphate. Reproduced from

Galactose, Encyclopaedia of Food Science, Food Technology and

Nutrition, Macrae R, Robinson RK and Sadler MJ (eds), 1993,

Academic Press.

tbl0001 Table 1 Lactose content of milk and dairy products

Food Lactose content (g per100 g)

Cows’ milk 4.7

Goats’ milk 4.6

Human milk 7.2

Butter Trace

Cream 2.0–3.2

Cheese (most types) Trace

Cottage cheese 1.4

Yogurt 3.2–4.8

From Paul AA and Southgate DAT (1978) McCance and Widdowson’s The

Composition of Foods, 4th edn. London: Her Majesty’s Stationery Office.

2844 GALACTOSE

in blood galactose levels after ingesting galactose

is directly related to the amount of galactose taken.

The maximum blood galactose level achieved and

the duration of elevated blood galactose levels

increase with increasing galactose load. This is in

marked contrast to the blood glucose response

to differing glucose loads, which is highly controlled,

primarily through the action of insulin.

0020 Blood glucose levels increase after galactose inges-

tion, which is not surprising considering that the

major metabolic route for galactose metabolism

results in glucose production. Metabolic studies

have found the rate of conversion of galactose to

glucose to be very efficient in humans. Excretion of

after

C-1-galactose is only slightly less than

after

C-1-glucose (galactose would need to be

converted to glucose prior to excretion as CO

). (See

Glucose: Maintenance of Blood Glucose Level.)

0021 A number of studies have reported that galactose

metabolism to glucose, as reflected by blood glucose

response to oral galactose, is more efficient in young

infants than in older children or adults. These find-

ings are, however, disputed.

0022 In humans, oral galactose results in a slight increase

in serum insulin levels, although animal studies have

found galactose to be incapable of stimulting insulin

release from the pancreas. It is believed to be the

increase in blood glucose levels after galactose inges-

tion that brings about the increase in blood insulin

levels. In galactosemic subjects, when galactose

cannot be converted to glucose, oral galactose does

not produce an increase in blood insulin levels.

0023 Various carbohydrates have been found to have

differing effects on metabolic rate (MR) and the re-

spiratory quotient (RQ). Equivalent meals of galact-

ose, galactose with glucose, and lactose produced

similar changes in MR but had different effects on

RQ in man. Galactose alone produces a greater and

more rapid increase in RQ than after the other test

meals mentioned, or after glucose alone. A larger RQ

suggests that a greater level of glucose oxidation is

occurring. (See Carbohydrates: Digestion, Absorp-

tion, and Metabolism; Metabolism of Sugars.)

0024 Galactose, lactose, and glucose given with galactose

loads have been shown to produce an increase in blood

lactate levels in fasting subjects. This is not found after

glucose loads. This result suggests a greater increase in

glycolysis after galactose-containing meals, as is also

suggested by RQ changes.

0025 If glucose is ingested with galactose, either as a

monosaccharide mixture or as lactose, the subsequent

blood galactose levels are much lower than if galact-

ose had been taken alone. It has been established that

this effect is not due to changes in the rate of absorp-

tion of galactose, and it cannot be brought about by

fructose. Intravenous insulin given at the same time as

oral galactose does not influence the blood galactose

response to oral galactose, even though the blood

glucose levels are low during such a procedure. Intra-

venous glucagon reduces the blood galactose response

to oral galactose and is accompanied by a large in-

crease in blood glucose. It would appear that, in the

presence of an elevated blood glucose level, blood

galactose levels are lower after a galactose load.

0026Blood galactose, glucose, and insulin responses to a

galactose and glucose mixture are the same in lactose-

intolerant and lactose-tolerant individuals.

0027Alcohol has the opposite effect to glucose on blood

galactose levels. Alcohol ingestion with oral galactose

increases the blood galactose response to galactose.

It is thought that the oxidation of alcohol in the

liver increases the level of reduced nicotinamide ad-

enine dinucleotide, which is essential for uridine

diphosphate-galactose epimerase activity. Hepatic

metabolism and uptake of galactose are therefore

inhibited.

0028The blood galactose, glucose, and insulin levels

after lactose are the same as after the equivalent

mixture of glucose and galactose. The blood galact-

ose response to lactose is increased if alcohol is taken

with the lactose.

Long-term Ingestion of Galactose

0029Lactose hydrolysate syrup fed at levels of 5–7% of

total energy intake for 10 weeks to men and women

caused a slight, but insignificant, increase in fasting

blood triglyceride levels in males but not females.

There are conflicting reports concerning the long-

term effects of feeding lactose on serum triglyceride

and cholesterol levels.

0030For many years, dietary lactose has been associated

with improved calcium absorption in humans and

animals. It would seem that in lactose-tolerant indi-

viduals, lactose and glucose given with galactose can

increase calcium absorption. It is not known how this

effect occurs. (See Calcium: Physiology.)

See also: Calcium: Physiology; Carbohydrates:

Digestion, Absorption, and Metabolism; Metabolism of

Sugars; Food Intolerance: Lactose Intolerance;

Glucose: Function and Metabolism; Maintenance of

Blood Glucose Level; Lactose