178 Introduction to Human Nutrition
Glucose metabolism in biotin defi ciency
Biotin is the coenzyme for one of the key enzymes of
gluconeogenesis, pyruvate carboxylase, and defi ciency
can lead to fasting hypoglycemia. In addition, biotin
acts via cell surface receptors to induce the synthesis
of phosphofructokinase and pyruvate kinase (key
enzymes of glycolysis), phospho-enolpyruvate
carboxykinase (a key enzyme of gluconeogenesis) and
glucokinase.
Rather than the expected hypoglycemia, biotin
defi ciency may sometimes be associated with hyper-
glycemia as a result of the reduced synthesis of gluco-
kinase. Glucokinase is the high Km isoenzyme of
hexokinase that is responsible for uptake of glucose
into the liver for glycogen synthesis when blood con-
centrations are high. It also acts as the sensor for
hyperglycemia in the β-islet cells of the pancreas;
metabolism of the increased glucose 6-phosphate
formed by glucokinase leads to the secretion of
insulin. There is some evidence that biotin supple-
ments can improve glucose tolerance in diabetes.
Lipid metabolism in biotin defi ciency
The skin lesions of biotin defi ciency are similar to
those seen in defi ciency of essential fatty acids, and
serum linoleic acid is lower than normal in biotin-
defi cient patients owing to impairment of the
elongation of PUFAs as a result of reduced activity of
acetyl-CoA carboxylase.
The impairment of lipogenesis also affects the
tissue fatty acid composition, with an increase in the
proportion of palmitoleic acid, mainly at the expense
of stearic acid, apparently as a result of increased fatty
acid desaturase activity in biotin defi ciency. Although
dietary protein and fat intake also affect tissue fatty
acid composition, the ratio of palmitoleic to stearic
acid may provide a useful index of biotin nutritional
status in some circumstances.
Biotin defi ciency also results in an increase in the
normally small amounts of odd-chain fatty acids
(mainly C15:0 and C17:0) in triacylglycerols, phos-
pholipids, and cholesterol esters. This is a result of
impaired activity of propionyl-CoA carboxylase,
leading to an accumulation of propionyl-CoA, which
can be incorporated into lipids in competition with
acetyl-CoA.
Safe and adequate levels of intake
There is no evidence on which to estimate require-
ments for biotin. Average intakes are between 10 μg/
day and 200 μg/day. Since dietary defi ciency does not
occur, such intakes are obviously more than adequate
to meet requirements.8.13 Pantothenic acid
Pantothenic acid (sometimes known as vitamin B 5 ,
and at one time called vitamin B 3 ) has a central role
in energy-yielding metabolism as the functional
moiety of coenzyme A (CoA) and in the biosynthesis
of fatty acids as the prosthetic group of acyl carrier
protein. The structures of pantothenic acid and CoA
are shown in Figure 8.18.
Pantothenic acid is widely distributed in all food-
stuffs; the name derives from the Greek for “from
everywhere,” as opposed to other vitamins that were
originally isolated from individual especially rich
sources. As a result, defi ciency has not been unequivo-
cally reported in human beings except in specifi c
depletion studies, most of which have used the antag-
onist ω-methyl-pantothenic acid.Absorption, metabolism, and metabolic
functions of pantothenic acid
About 85% of dietary pantothenic acid is as CoA and
phosphopantetheine. In the intestinal lumen these are
hydrolyzed to pantetheine; intestinal mucosal cells
have a high pantetheinase activity and rapidly hydro-
lyze pantetheine to pantothenic acid. The intestinal
absorption of pantothenic acid seems to be by simple
diffusion and occurs at a constant rate throughout the
length of the small intestine; bacterial synthesis may
contribute to pantothenic acid nutrition.
The fi rst step in pantothenic acid utilization is phos-
phorylation. Pantothenate kinase is rate limiting, so
that, unlike vitamins that are accumulated by meta-
bolic trapping, there can be signifi cant accumulation
of free pantothenic acid in tissues. It is then used for
synthesis of CoA and the prosthetic group of acyl
carrier protein. Pantothenic acid arising from the turn-
over of CoA and acyl carrier protein may be either
reused or excreted unchanged in the urine.Coenzyme A and acyl carrier protein
All tissues are capable of forming CoA from panto-
thenic acid. CoA functions as the carrier of fatty acids,
as thioesters, in mitochondrial β-oxidation. The
resultant two-carbon fragments, as acetyl-CoA, then
undergo oxidation in the citric acid cycle. CoA also
functions as a carrier in the transfer of acetyl (and