Stephanie Hickey
Nutrition 445
Shearer
28 April 2014
Case Study 4
Obesity:
A 19-year-old woman sought medical help because she was 30 kg overweight. Most of her
excess weight was in the form of adipose tissue. A medical history revealed that her diet was
extremely poor. Much of her caloric intake was carbohydrate – candy, cookies, cake, soft drinks,
and beer; her dietary fat intake was actually quite moderate.
Questions:
1. How is it possible to form excess amounts of triglyceride in the body if a diet contains
predominately carbohydrate?
Her diet seems to consist mostly of simple carbohydrates. Simple carbohydrate consists on
monosaccharide such as, glucose, fructose, and galactose. Once transport of these
monosaccharide’s across the wall of the intestine, they enter the portal circulation, where
they are then carried to the liver. During fructose metabolism, fructose can enter the liver
pathways. This leads to an increase in fatty acid synthesis, esterification of fatty acids and
VLDL secretion which raises the serum of triacylglycerol’s and LDL cholesterol
concentrations. Fructose goes through glycolysis through a much faster rate within the
liver than does glucose because it avoids the regulatory step catalyzed by
phosphofructokinase. Fructose is then converted to the end product of glycolysis,
pyruvate. Pyruvate then converts to acetyl-CoA and enters lipogenesis. To begin
lipogenesis, acetyl-CoA is converted into malonyl-CoA. Fatty acids that are made from
lipogenesis are stored as triglycerides in the adipose tissue. Also, both fructose and
galactose can be transformed into glucose derivatives that make them have the same fate as
glucose and can be stored as liver glycogen Due to any extra glucose that is not needed for
energy or glycogenesis may be transformed into fatty acids. The glycerol that is essential
for triacylglycerol is created from triose phosphate. Sent triacylglycerol’s can be formed
from glucose, hepatic production is enhanced when the diet is high in carbohydrates.
(Gropper & Smith, 2013).
Hickey 2
(Grooper & Smith, 2013)
2. How does acetyl CoA generated inside the mitochondria reach the cytoplasm for use by
the fatty acid biosynthetic pathway?
The mitochondria are selectively permeable and acetyl-CoA isn’t permeable to the
mitochondria membrane. Almost all of acetyl-CoA that is created in metabolism happens
in the mitochondria. It is produced from pyruvate, fatty acid oxidation and degradation of
carbon backbone of amino acids through the TCA cycle. Acetyl-CoA is the starter
molecule for fatty acid biosynthesis. The synthesis of fatty acids occurs in the cytosol, but
acetyl-CoA formed in the mitochondria matrix can’t leave through the mitochondria
membrane. So to get acetyl-CoA from the mitochondria into the cytoplasm, a reaction with
oxaloacetate to form citrate has to occur because it can pass through the inner membrane.
When in the cytosol, citrate lyase transforms citrate back to oxaloacetate and acetyl-CoA
(Gropper & Smith, 2013).
Figure 2:
(Grooper & Smith, 2013)
Hickey 3
3. How might the carbohydrate ingested by this patient supply the NADPH needed for fatty
acid biosynthesis?
The NADPH is formed by the pentose phosphate pathway within the cytosol. One of the
important functions of the pathway is the reduced cosubstrate NADPH, which is used for
metabolic functions such as fatty acid biosynthesis. The cells of tissues that are active in
the synthesis of fatty acids, for example, the mammary gland, adipose tissue, adrenal
cortex, and the liver, need NADPH. These tissues recover pentose phosphates back to
glucose-6-phosphate to repeat the cycle to ensure there is an abundant supply of NADPH.
The pathway reactions that feature the dehydrogenase reactions and the formation of
NADPH from NADP+ are the oxidative reaction of the pathway (Gropper & Smith, 2013).
4. Devise a test that would indicate whether this patient could mobilize the triglyceride that
is stored in her adipose tissue.
Testing the blood or enzymatic activity would indicate whether this patient could mobilize
the triglyceride and free fatty acids that is stored in her adipose tissue. Adipose tissue
absorbs triacylglycerol’s (TAG) and cholesterol from chylomicrons through the action of
lipoprotein lipase (LPL). LPL is used in lipolysis, which is responsible for hydrolyzing
TAG into glycerol and three fatty acids. Adipocyte is the major site of storage for
triacylglycerol’s. The triacylglycerol’s are constantly in a state of turnover, meaning
consistent lipolysis is countered by consistent re-esterification to form triacylglycerol’s.
Plasma glycerol levels may be used to indicate the turnover rate of TAG in adipose tissue.
Insulin levels may also be used to measure the mobilization of TAG; sent insulin inhibits
HSL, which hydrolyzes stored TAG, which results in TAG accumulation. If TAG and FFA
are highly concentrated in the blood, lipolysis is happening and TAG is being mobilized
from adipose tissue (Gropper & Smith, 2013).
Furthermore, a lipid panel should be taken when the patient is fasted because lipolysis
occurs in a fasted state. The lipid panel will also check for the activity of the hormone
epinephrine, norepinephrine, ACTH, and glucagon that activate HSL (Gropper & Smith,
2013).
5. What kind of unsaturated fatty acid can be synthesized from glucose? What metabolic
reactions would be involved in this process?
Synthesis of unsaturated fatty acids starts with the synthesis of saturated fatty acids.
Asides from essential fatty acids, linoleic and α-linoleic acid, our body has the ability to
synthesize fatty acids from simple precursors. Glucose crosses the cell membrane by the
GLUT4 transporter and is phosphorylated by hexokinase. Glycolysis converts glucose into
glucose-6-phosphate; which eventually results in pyruvate where they are oxidized to
Hickey 4
acetyl-CoA. Both fat and carbohydrate catabolism meet at acetyl-CoA. In fatty acid
synthesis, acetyl-CoA forms into Malonyl-CoA, catalyzed by acetyl-CoA carboxylase. This
reaction occurs in the cytosol (Gropper & Smith, 2013).
Figure 4:
(Gropper & Smith, 2013)
Unsaturated fatty acids are made from desaturases. Humans lack Δ12 and Δ15
desaturases, therefore, linoleic acid (18:2 Δ9,12) and α-linolenic acid (18:3 Δ9,12,15) are
essential because they create double bonds at these positions. Fatty acid desaturation
reaction, palmitate and stearate can be transformed into Δ9 monounsaturated fatty acids,
such as, palmitoleic acid and oleic acid. These reactions are catalyzed by mixed-function
oxidases. Mixed-function oxidases are where two different substrates are oxidized, the
fatty acid and NADPH. Fatty acid is oxidized by the release of hydrogen atoms to create
double bonds. Oxygen is the last hydrogen and electron acceptor to make water (Gropper
& Smith, 2013).
Hickey 5
Works Cited
Gropper, Sareen S., and Jack L. Smith. Advanced Nutrition and Human Metabolism. 6th ed.
Belmont: Wadsworth Cengage Learning, 2013. Print.