Page 153 - Color Atlas of Biochemistry

P. 153

144 Metabolism

Regulation to theinnermembrane(1) or by lipid-soluble
substances that can transport protons
Theamountof nutrientdegradation andATP through the membrane, such as 2,4-
synthesis have to be continually adjusted to dinitrophenol (DNP, 2). Thermogenin (uncou-
the body’s changing energy requirements. pling protein-1, UCP-1, 3)—an ion channel
The need to coordinate the production and (see p. 222) in mitochondria of brown fat tis-
consumption of ATP is already evident from sue—is a naturally occurring uncoupler.
thefactthatthe total amounts of coenzymes Brownfat is found, for example,innewborns
in the organism are low. The human body and in hibernating animals, and serves exclu-
forms about 65 kg ATP per day, but only con- sively to generate heat. In cold periods, nor-
tains 3–4 g of adenine nucleotides (AMP, ADP, epinephrine activates the hormone-sensitive
and ATP). Each ADP molecule therefore has to lipase (see p. 162). Increased lipolysis leads
be phosphorylated to ATP and dephosphory- to the production of large quantities of free
+
lated again many thousand times a day. fatty acids. Like DNP, these bind H ions in the
intermembrane space, pass the UCP in this
form, and then release the protons in the
A. Respiratory control
matrix again. This makes fatty acid degrada-
The simple regulatory mechanism which en- tion independent of ADP availability—i. e., it
sures that ATP synthesis is “automatically” takes place at maximum velocity and only
coordinated with ATP consumption is known produces heat (A). It is becoming increasingly
as respiratory control.It is based on the fact clear that there are also UCPs in other cells,
that the different parts of the oxidative phos- whichare controlled by hormones suchas
phorylation process are coupled via shared thyroxine (see p. 374). This regulates the
coenzymes and other factors (left). ATP yield and what is known as the basal
If a cell is not using any ATP, hardly any ADP metabolic rate.
will be available in the mitochondria. Without
ADP, ATP synthase (3)is unable to break down
the proton gradient across the inner mito- C. Regulation of the tricarboxylic acid cycle
chondrial membrane. This in turn inhibits The most important factor in the regulation of
+
electron transport in the respiratory chain the cycle is the NADH/NAD ratio. In addition
+
(2), which means that NADH+H can no lon- to pyruvate dehydrogenase (PDH) and oxoglu-
+
ger be reoxidized to NAD . Finally, the result- tarate dehydrogenase (ODH; see p. 134), cit-
+
ing high NADH/NAD ratio inhibits the tricar- rate synthase and isocitrate dehydrogenase are
+
boxylic acid cycle (C), and thus slows down also inhibited by NAD deficiency or an excess
+
the degradation of the substrate SH 2 (1). Con- of NADH+H . With the exception of isocitrate
versely, high rates of ATP utilization stimulate dehydrogenase, these enzymes are also sub-
nutrient degradation and the respiratory ject to product inhibition by acetyl-CoA, suc-
chain via the same mechanism. cinyl-CoA, or citrate.
If the formation of a proton gradient is Interconversion processes (see p. 120) also
prevented (right), substrate oxidation (1) play an important role. They are shown here
and electron transport (2)proceed much in detail using the example of the PDH com-
more rapidly. However, instead of ATP, only plex (see p. 134). The inactivating protein
heat is produced. kinase [1a] is inhibited by the substrate pyru-
vate and is activated by the products acetyl-
+
CoA and NADH+H .The protein phosphatase
B. Uncouplers
[1b]—like isocitrate dehydrogenase [3] and the
2+
Substances that functionally separate oxida- ODH complex [4]—is activated by Ca .This is
tion and phosphorylation from one another particularly important during muscle con-
are referred to as uncouplers. They break traction, when large amounts of ATP are
down the proton gradient by allowing H + needed. Insulin also activates the PDH com-
ions to pass from the intermembrane space plex (through inhibition of phosphorylation)
back into the mitochondrial matrix without and thereby promotes the breakdown of glu-
the involvement of ATP synthase. Uncoupling cose and its conversion into fatty acids.
effects are produced by mechanical damage

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