Biomedical Engineering Reference
In-Depth Information
pressure has a regulatory effect on rate of glycolysis, known as the Pasteur effect. The rate of
glycolysis under anaerobic conditions is higher than that under aerobic conditions. In the
presence of oxygen, ATP yield is high, since the TCA cycle and electron transport chain
are operating. As a result of high levels of ATP, ADP and H 3 PO 4 become limiting, and phos-
phofructokinase becomes inhibited. Also, some enzymes of glycolysis with -SH groups are
inhibited by high levels of oxygen. A high NADH/NAD þ ratio also reduces the rate of
glycolysis.
Certain enzymes of the Krebs cycle are also regulated by feedback inhibition. Pyruvate
dehydrogenase is inhibited by ATP, NADH, and acetyl-CoA and activated by ADP, AMP,
and NAD þ . Similarly, citrate synthase is inactivated by ATP and activated by ADP and
AMP; succinyl-CoA synthetase is inhibited by NAD þ . In general, high ATP/ADP and
NADH/NAD þ ratios reduce the processing rate of the TCA cycle.
Several steps in the electron transport chain are inhibited by cyanide, azide, carbon
monoxide, and certain antibiotics, such as amytal. Such inhibition is important due to its
potential to alter cellular metabolism.
10.7.7. Metabolism of Nitrogenous Compounds
Most of the organic nitrogen compounds have an oxidation level between carbohydrates
and lipids. Consequently, nitrogenous compounds can be used as nitrogen, carbon, and
energy source. Proteins are hydrolyzed to peptides and further to amino acids by proteases.
Amino acids are first converted to organic acids by deamination (removal of amino group).
Deamination reaction may be oxidative, reductive, or dehydrative, depending on the enzyme
systems involved. A typical oxidative deamination reaction can be represented.
H þ (10.45)
Ammonia released from deamination is utilized in protein and nucleic acid synthesis as
a nitrogen source, and organic acids can be further oxidized for energy production (ATP).
Transamination is another mechanism for conversion of amino acids to organic acids and
other amino acids. The amino group is exchanged for the keto group of
NAD þ /
R e CH
ð
NH
2 Þe COOH
þ
H
O
þ
R e CO e COOH
þ
NH
3 þ
NADH
þ
2
a
-keto acid. A typical
transamination reaction is
glutamic acid
þ
oxaloacetic acid
/ a-
keto glutaric acid
þ
aspartic acid
(10.46)
Nucleic acids can also be utilized by many organisms such as carbon, nitrogen, and energy
source. The first step in nucleic acid utilization is enzymatic hydrolysis by specific nucleases
hydrolyzing RNA and DNA. Nucleases with different specificities hydrolyze different bonds
in nucleic acid structure, producing ribose/deoxyribose, phosphoric acid, and purines/
pyrimidines. Sugar molecules are metabolized by glycolysis and the TCA cycle, producing
CO 2 and H 2 O under aerobic conditions. Phosphoric acids are used in ATP, phospholipid,
and nucleic acid synthesis.
Purines/pyrimidines are degraded into urea and acetic acid and then to ammonia and
CO 2 . For example, the hydrolysis of adenine and uracil can be represented as follows:
adenine
CO
2 þ
NH
3 þ
acetic acid
þ
urea
/ 5
NH
3 þ 5
CO
(10.47)
/
2
uracil
alanine
þ
NH
3 þ
CO
2 / 2
NH
3 þ 4
CO
(10.48)
/
2
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