Chapter 29 Biosynthetic Pathways
29.1
Your text states in Section 29.1 several reasons why anabolic pathways are different from
catabolic:
(1) Duplication of pathways adds flexibility. If the normal biosynthetic pathway is blocked,
the body can use the reverse of the catabolic pathway to make the necessary metabolites.
(2) Separate pathways allow the body to overcome the control of reactions by reactant
concentration (Le Chatelier’s principle).
(3) Different pathways provide for separate regulation of each pathway. Although there are
many differences between anabolism and catabolism, we will also note similarities that allow
for coordinated regulation and proper balancing of concentrations.
29.2
Glycogen degradation is carried out by the enzyme glycogen phosphorylase which uses as
the cleavage reagent, inorganic phosphate. The concentration of inorganic phosphate is
relatively high in cells, therefore one would expect that this leads to rapid breakdown of
glycogen. We have another pathway responsible for glycogen synthesis which does not use
inorganic phosphate, but maintains essential levels of glycogen.
29.3
The cellular concentration of inorganic phosphate, a reagent used in phosphorylation
reactions, is very high; therefore, the reaction is driven in the direction of glycogen
breakdown. In order to ensure the presence of glycogen when needed, it must have an
alternate synthetic pathway.
29.4
Most anabolic and catabolic reactions do not occur in the same cellular location. Most
catabolism (except glycolysis) occurs in the mitochondria and most anabolic reactions occur
in the cytoplasm. Having different locations for anabolism and catabolism allows cells to
better regulate the opposing processes of synthesis and degradation pathways.
29.5
The major difference between the overall reactions of photosynthesis and respiration is the
direction of the reactions. They are the reverse of each other:
6CO2 + 6H2O → C6H12O6 + 6O2
photosynthesis
C6H12O6 + 6O2 → 6CO2 + 6H2O
respiration
29.6
In photosynthesis, the source of:
(a) carbon for carbohydrate synthesis: carbon dioxide
(b) hydrogen for carbohydrate synthesis: water
(c) energy: the sun
29.7
A compound that can be used for gluconeogenesis:
(a) From glycolysis: pyruvate
(b) From the citric acid cycle: oxaloacetate
(c) From amino acid oxidation: alanine
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29.8
Glucose is activated for glycogen synthesis by linkage via a phosphate ester bond to UDP.
29.9
The brain obtains most of its energy from glucose that is supplied by the blood. Thebrain has
little or no capacity to store glucose in glycogen. During starvation, glucose for the brain will
come from glycogen that is stored primarily in the liver. Since glucose concentrations are
very low in starvation, the liver glycogen is synthesized from glucose that is produced from
pyruvate, lactate, amino acids, etc. The glucose is formed by gluconeogenesis. Brain cells are
also able to obtain some energy from degradation of the ketone bodies.
29.10 Most of the enzymes used for gluconeogenesis are the same as those that are used for
glycolysis. Of the approximately 11 enzymes used for gluconeogenesis and glycolysis, 4 are
unique to the gluconeogenesis pathway. (Figure 29.1).
29.11 Maltose is a disaccharide that is composed of two glucose units linked by an α-1,4glycosidic bond (Section 20.4C). We know that in glycogen synthesis, the UDP-glucose can
combine with another glucose to add to the glycogen chain. Therefore, we could envision a
similar reaction to make maltose. The enzyme might be called maltose synthase:
UDP-glucose + glucose
maltose + UDP
29.12 (a) The letter n refers to the number of glucose residues in a glycogen polymer.
(b) The number of glucose residues may be as high as 1,000,000.
29.13 Uridine triphosphate (UTP) is a nucleoside triphosphate similar to ATP. The constituents are:
a nitrogen base, uracil; a sugar, ribose; and three phosphates.
29.14 The carbon atoms used in fatty acid synthesis have their origin in acetyl CoA.
29.15 (a) The biosynthesis of fatty acids occurs primarily in the cell cytoplasm. Here acetyl CoA is
used to make palmitoyl CoA. Extension of the carbon chain to stearate and desaturation to
form carbon-carbon double bonds occurs in mitochondria and the endoplasmic reticulum.
(b) Fatty acid catabolism does not occur in the same location as anabolism. The enzymes for
β-oxidation are located in the mitochondrial matrix.
29.16 The acyl carrier protein (ACP) is not an enzyme, but rather a molecule that binds the
acyl groups involved in fatty acid synthesis and rotates them around to enzymes that
catalyze the reactions.
29.17 In fatty acid synthesis, the compound that is added repeatedly to the enzyme, fatty acid
synthase, is malonyl CoA, which has a three-carbon chain.
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29.18 (a) The first enzyme in fatty acid synthesis is fatty acid synthase.
(b) The enzyme picks up the first two carbons to start the fatty acid chain. The enzyme picks
up an acetyl group from acetyl-ACP. The acetyl group is transferred from the -SH group of
ACP to the -SH group of the fatty acid synthase. The acetyl group (C-2) on the synthase is
then condensed with malonyl-ACP (C-3) to produce acetoacetyl-ACP (C-4) and carbon
dioxide (see Section 29.3).
29.19 The carbon dioxide is released from malonyl-ACP which leads to the addition of two carbons
to the growing fatty acid chain.
29.20 CoA, ACP, and fatty acid synthase all have a functional sulfhydryl group (-SH) that is
involved in activating acyl groups.
29.21 If one considers only what is happening to the fatty acid, removal of two hydrogens and two
electrons, then it looks like oxidation only. However, the reaction is much more complex and
involves a cofactor, NADPH and the substrate, oxygen. Both the fatty acid and NADPH
undergo two-electron oxidation. The four electrons and protons are used to reduce oxygen to
water:
O2 + 4H+ + 4e2H2O
29.22 The fatty acid synthase complex can make saturated acyl chains up to 16 carbons long
(palmitate).
(a) Oleic: cannot be made by fatty acid synthase.
(b) Stearic: cannot be made by fatty acid synthase.
(c) Myristic: fewer than 16 carbons so it can be made by the synthase.
(d) Arachidonic: cannot be made by the synthase.
(e) Lauric: fewer than 16 carbons so it can be made by the synthase.
29.23 The only structural difference between NADH and NADPH is a phosphate group on one of
the ribose units of NADPH. When considering the binding of NADPH to an NADH-requiring
enzyme, two factors are important—size and charge. The phosphate makes the NADPH bulky
and the NADH binding site may not be able to accommodate the larger size of the cofactor. In
terms of charge, NADPH has two negative charges not present in NADH. The NADH
binding site may have amino acid residues that have negatively-charged side chains like Glu
or Asp. These would repel NADPH, but could hydrogen bond to the free hydroxyl group in
NADH.
29.24 Yes, the fatty acids that are incorporated into membrane phospholipids and glycolipids are
synthesized in the same way as the fatty acids stored in triglycerides.
29.25 Humans have enzymes that catalyze the oxidation of saturated fatty acids to monounsaturated fatty acids with the double bond between carbons 9 and 10. For example, we can
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make palmitoleic acid from palmitic acid and oleic acid from stearic acid. Humans do not
have enzymes that introduce a double bond beyond the 10th carbon. Therefore humans cannot
make linoleic (double bonds at carbons 9-10 and 12-13) or linolenic acid (double bonds at
carbons 9-10, 12-13, and 15-16). Those fatty acids are essential in the diet.
29.26 The building blocks to synthesize the phospholipid are: glycerol 3-phosphate (made from
the reduction of dihydroxyacetone phosphate), the CoA esters of palmitate and laurate,
and the amino acid serine in an activated form.
29.27 To make a glucoceramide, sphingosine is reacted with an acyl CoA that adds a fatty acid in
amide linkage. Glucose is added to the hydroxyl group of sphingosine using the activated
form, UDP-glucose (see Section 21.8).
29.28 The enzyme HMG reductase is a key regulatory enzyme in the biosynthesis of cholesterol.
The enzyme is inhibited by cholesterol or some derivative of cholesterol in order to control
the amount of cholesterol in cells. The enzyme is a key target for the cholesterol-lowering
drugs like lovastatin and lipitor that inhibit the enzyme.
29.29 All of the carbons in cholesterol orginate in acetyl CoA. An important intermediate in the
synthesis of the steroid is a C-5 fragment called isopentenyl pyrophosphate:
3AcetylCoA
mevalonate
C-2
C-6
isopentenyl pyrophosphate + CO2
C-5
29.30 The amino acid Glu is synthesized by the reaction of α-ketoglutarate + ammonium ion +
NADH. The reverse of this reaction, which is the oxidative deamination of Glu, produces
an α-keto acid (α-ketoglutarate) that is an intermediate in the citric acid cycle.
29.31 An amino acid is synthesized by the reverse of oxidative deamination (Section 29.5).
The amino acid product is aspartate. NADH will be oxidized to NAD+.
29.32 In a transamination reaction where glutamate is the amino donor and asparagines is created,
the other molecules in the reaction would be α-ketoglutarate and the keto form of
asparagines, which would look like the molecule below:
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29.33 The products of the transamination reaction shown are valine and α-ketoglutarate.
O
(CH3 ) 2 CH-C-COO- + -OOC-CH2 -CH2 -CH-COOThe keto form
of valine
NH3 +
Glutamate
O
(CH3 ) 2 CH-CH-COO + OOC-CH2 -CH2 -C-COO-
NH3 +
Valine
-
α-Ketoglutarate
29.34 Photosystems I and II are located in the plant organelles called chloroplasts. They participate
in the light reaction of photosynthesis: chlorophyll absorbs light from the sun and activates
an electron-transport chain that forms oxygen, ATP, and NADPH.
29.35 The carbon dioxide that is used to make carbohydrates in plants is reduced by the cofactor
NADPH.
29.36 Prenylation of a protein attaches a long, hydrocarbon unit (up to 10-15 carbon atoms in
multiple C5 isoprene units) which allows the protein to associate with hydrophobic elements
like a membrane. An unprenylated Ras protein is not able to interact with the membrane and
thus, not able to transduct a signal through the membrane.
29.37 (a) The colored urine of blue diaper syndrome is caused by indigo blue dye.
(b) It is formed from the oxidation of the amino acid tryptophan.
29.38 If the proteins one eats do not contain all 20 amino acids, there will be little effect if
nonessential amino acids are missing. However, lack of essential amino acids will mean
that proteins cannot be synthesized in the body, and protein deficiency will result.
29.39 The bonds that connect the nitrogen bases to the ribose units are β-N-glycosidic bonds
just like those found in nucleotides.
29.40 The C-3 fragment, a malonyl group, is carried by ACP, acyl carrier protein.
29.41 The amino acid produced by transfer of the amino group is Phe.
29.42 No. Ras protein is a GTP-binding protein involved in signal transduction only in its
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prenylated form. It is encoded by an oncogene, thus mutations may cause cancer. Some
mutations that inhibit prenylation of Ras cause the cell to die. Other mutations of prenylated
Ras may cause uncontrolled cell growth.
29.43 The structure of a lecithin (also phosphatidyl choline) is in Section 21.6. Its synthesis
requires activated glycerol, two activated fatty acids, and activated choline. Since each
activation requires one ATP, the total number of ATP molecules needed is four.
29.44 Towards the formation of α-hydroxybutyrate. When the human body is exposed to cold
temperatures, energy metabolism must be increased to generate heat. Increasing the
concentration of mainstream metabolites would do this. α-Ketoglutarate, resulting from
the deamination of glutamate, would feed directly into the citric acid cycle and enhance
metabolic rates.
29.45 The compound that reacts with Glu in a transamination reaction to form serine is
3-hydroxypyruvate. The reaction is shown below:
29.46 The C-10 and C-15 intermediates in cholesterol synthesis are geranyl pyrophosphate and
farnesyl pyrophosphate, respectively.
29.47 HMG-CoA is 3-hydroxy 3-methylglutaryl-CoA. Its structure is shown in Section 29.4.
Carbon 1 is the carbonyl group linked to the thiol group of CoA.
29.48 The statement is also true for photosynthesis. The overall reaction for photosynthesis is
shown in Problem 29.5 and Reaction 29.3. The carbon in carbon dioxide is in its most
highly oxidized form. In the biosynthesis of carbohydrates, the carbon atoms become
reduced to aldehyde and alcohol functional groups. Both of these groups come as a result
of the reduction of the carbon dioxide.
29.49 Heme is a porphyrin ring with an iron ion at the center. Chlorophyll is a porphyrin ring with
a magnesium ion at the center.
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29.50 Fatty acid synthase produces even-numbered chains up to 16 carbons, palmitate. Elongation
of the C-16 acids occurs by a different enzyme system in mitochondria and the endoplasmic
reticulum.
29.51 Fatty acid biosynthesis takes place in the cytoplasm, requires NADPH, and uses malonylCoA. Fatty acid catabolism takes place in the mitochondrial matrix, produces NADH and
FADH2, and has no requirement for malonyl-CoA.
29.52 In plants, the source of energy for carbohydrate synthesis is the sun; in animals, it is the
chemical energy of ATP.
29.53 Photosynthesis has high requirements for light energy from the sun.
29.54 It is possible to get all essential nutrients from a vegan diet, but getting enough protein
with all the essential amino acids takes planning. It is easier to get essential nutrients
from a diet that allows animal products because many animal proteins contain all the
essential amino acids.
29.55 Lack of essential amino acids would hinder the synthesis of the protein part.
Gluconeogenesis can produce sugars even under starvation conditions.
29.56 For long term health, we must have some of all of the essential nutrients. However, in
theory, we would be better off for longer periods of time if we had to limit carbohydrates
because our bodies can make carbohydrates from amino acids, assuming we had
sufficient amino acids. This would not be an optimal situation as it would result in the
production of a lot of ketone bodies in the blood.
29.57 Separation of catabolic and anabolic pathways allows for greater efficiency, especially in
control of the pathways. It allows for both processes to be going on simultaneously in the
body as conditions can be different in different cell compartments.
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