Page 163 - Color Atlas of Biochemistry
P. 163
154 Metabolism
Gluconeogenesis from lactate or amino acids is therefore ini-
tially transported into the mitochondrial ma-
Some tissues, such as brain and erythrocytes, trix, and—in a biotin-dependent reaction cat-
depend on a constant supply of glucose. If the alyzed by pyruvate carboxylase—is carboxy-
amount of carbohydrate taken up in food is lated there to oxaloacetate. Oxaloacetate is
not suf cient, the blood sugar level can be also an intermediate in the tricarboxylic acid
maintained for a limited time by degradation cycle. Amino acids with breakdown products
of hepatic glycogen (see p. 156). If these re- that enter the cycle or supply pyruvate can
serves are also exhausted, de-novo synthesis therefore be converted into glucose (see
of glucose (gluconeogenesis)begins. The liver p. 180).
is also mainly responsible for this (see p. 310), [3] The oxaloacetate formed in the mito-
but the tubular cells of the kidney also show a chondrial matrix is initially reduced to ma-
high level of gluconeogenetic activity (see late, which can leave the mitochondria via
p. 328). The main precursors for gluconeo- inner membrane transport systems (see
genesis are amino acids derived from muscle p. 212).
proteins. Another important precursor is [4] In the cytoplasm, oxaloacetate is re-
lactate, which isformed in erythrocytesand formed and then converted into phospho-
muscle proteins when there is oxygen de- enol pyruvate by a GTP-dependent PEP car-
ficiency. Glycerol produced from the degrada- boxykinase. The subsequent steps up to fruc-
tion of fats can also be used for gluconeogen- tose 1,6-bisphosphate represent the reverse
esis. However, the conversion of fatty acids of the corresponding reactions involved in
into glucose is not possible in animal metab- glycolysis. One additional ATP per C 3 frag-
olism (seep. 138). Thehuman organism can ment is used for the synthesis of 1,3-bisphos-
synthesize several hundred grams of glucose phoglycerate.
per day by gluconeogenesis. Two gluconeogenesis-specific phosphat-
ases then successively cleave off the phos-
phate residues from fructose 1,6-bisphos-
A. Gluconeogenesis
phate. In between these reactions lies the
Many of the reaction steps involved in gluco- isomerization of fructose 6-phosphate to glu-
neogenesis are catalyzed by the same en- cose 6-phosphate—another glycolytic reac-
zymes that are used in glycolysis (see tion.
p. 150). Other enzymes are specific to gluco- [5] The reaction catalyzed by fructose
neogenesis and are only synthesized, under 1,6-bisphosphatase is an important regulation
the influence of cortisol and glucagon when point in gluconeogenesis (see p. 158).
needed (see p. 158). Glycolysis takes place [6] The last enzyme in the pathway, glucose
exclusively when needed in the cytoplasm, 6-phosphatase, occurs in the liver, but not in
but gluconeogenesis also involves the mito- muscle. It is located in the interior of the
chondria and the endoplasmic reticulum (ER). smooth endoplasmic reticulum. Specific
Gluconeogenesis consumes 4 ATP (3 ATP + 1 transporters allow glucose 6-phosphate to
GTP) perglucose—i. e., twiceasmany asgly- enter the ER and allow the glucose formed
colysis produces. there to return to the cytoplasm. From there,
it is ultimately released into the blood.
[1] Lactate as a precursor for gluconeogen-
esis is mainly derived from muscle (see Cori Glycerol initially undergoes phosphoryla-
cycle, p. 338) and erythrocytes. LDH (see tion at C-3 [7]. The glycerol 3-phosphate
+
p. 98) oxidizes lactate to pyruvate, with formed is then oxidized by an NAD -depen-
+
NADH+H formation. dent dehydrogenase to form glycerone 3-
[2] The first steps of actual gluconeogenesis phosphate [8] and thereby channeled into
take place in the mitochondria. The reason for gluconeogenesis. An FAD-dependent mito-
this “detour” is the equilibrium state of the chondrial enzyme isalsoable tocatalyze
pyruvate kinase reaction (see p. 150). Even this reaction (known as the “glycerophos-
coupling to ATP hydrolysis would not be suf- phate shuttle”; see p. 212).
ficient to convert pyruvate directly into phos-
phoenol pyruvate (PEP). Pyruvate derived
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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