Page 319 - Color Atlas of Biochemistry

P. 319

310 Tissues and organs

Carbohydrate metabolism and therefore cannot be converted into oxalo-
acetic acid, the precursor for gluconeogenesis.
Besides fatty acids and ketone bodies, glucose
is the body’s most important energy supplier.
The concentration of glucose in the blood (the B. Fructose and galactose metabolism
“blood glucose level”) is maintained at Fructose is mainly metabolized by the liver,
–1
4–6 mM (0.8–1.0 g L ) by precise regula- which channels it into glycolysis (left half of
tion of glucosesupplying and glucose-utilizing the illustration).
processes. Glucose suppliers include the in- Aspecial ketohexokinase [1] initially phos-
testines (glucose from food), liver, and kid- phorylates fructose into fructose 1-phos-
neys. The liver plays the role of a “glucostat” phate. Thisisthen cleaved by an aldolase
(see p. 308). [2], which is also fructose-specific, to yield
The liver is also capable of forming glucose glycerone 3-phosphate (dihydroxyacetone
by converting other sugars—e. g., fructose and phosphate) and glyceraldehyde.Glycerone
galactose—or by synthesizing from other me- 3-phosphate is already an intermediate of
tabolites. The conversion of lactate to glucose glycolysis (center), while glyceraldehyde
in the Cori cycle (see p. 338) and the conver- can be phosphorylated into glyceraldehyde
sion of alanine to glucose with the help of the 3-phosphate by triokinase [3].
alanine cycle (see p. 338) are particularly im- To a smaller extent, glyceraldehyde is also
portant for the supply of erythrocytes and reduced to glycerol [4] or oxidized to glycer-
muscle cells. ate, which can be channeled into glycolysis
Transporters in the plasma membrane of following phosphorylation (not shown). The
hepatocytes allow insulin-independent trans- reduction of glyceraldehyde [4] uses up
port of glucose and other sugars in both di- NADH. As the rate of degradation of alcohol
rections. In contrast to muscle, the liver pos- in the hepatocytes is limited by the supply of
+
sesses the enzyme glucose-6-phosphatase, NAD , fructose degradation accelerates alco-
which can release glucose from glucose-6- hol degradation (see p. 320).
phosphate. Outside of the liver, fructose is channeled
into the sugar metabolism by reduction at C-2
to yield sorbitol and subsequent dehydration
A. Gluconeogenesis: overview
at C-1 to yield glucose (the polyol pathway;
Regeneration of glucose (up to 250 g per day) not shown).
mainly takes place in the liver. The tubule Galactose is also broken down in the liver
cells of the kidney are also capable of carrying (right side of the illustration). As is usual with
out gluconeogenesis, but due to their much sugars, the metabolism of galactose starts
smaller mass, their contribution only repre- with a phosphorylation to yield galactose
sents around 10% of total glucose formation. 1-phosphate [5]. The connection to the glu-
Gluconeogenesis is regulated by hormones. cose metabolism is established by C-4 epime-
Cortisol, glucagon, and epinephrine promote rization to form glucose 1-phosphate.How-
gluconeogenesis, while insulin inhibits it ever, thisdoesnot take place directly. Instead,
(see pp. 158, 244). a transferase [6] transfers a uridine 5 -mono-
The main precursors of gluconeogenesis in phosphate (UMP) residue from uridine di-
the liver are lactate from anaerobically work- phosphoglucose (UDPglucose) to galactose
ing muscle cells and from erythrocytes, 1-phosphate. This releases glucose 1-phos-
glucogenic amino acids from the digestive phate, while galactose 1-phosphate is con-
tract and muscles (mainly alanine), and verted into uridine diphosphogalactose (UDP-
glycerol from adipose tissue. The kidney galactose). This then is isomerized into UDP-
mainly uses amino acids for gluconeogenesis glucose. The biosynthesis of galactose also fol-
(Glu, Gln; see p. 328). lows this reaction pathway, which is freely
In mammals, fatty acids and other suppli- reversible up to reaction [5]. Genetic defects
ers of acetyl CoA are not capable of being used of enzymes [5] or [6] can lead to the clinical
for gluconeogenesis, as the acetyl residues picture of galactosemia.
formed during β-oxidation in the tricarbox-
ylic acid cycle (see p. 132) are oxidized to CO 2

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