Terms for a Medical Student:

1. Glycolysis
a. Metabolic pathway that converts glucose to pyruvate.
b. Produces ATP.
c. Catabolic.

2. Gluconeogenesis
a. Synthesis of glucose from amino acids, pyruvate, and other non-
carbohydrate forms.
b. Uses ATP.
c. Anabolic.

3. Glycogenolysis
a. Breakdown of glycogen to glucose.
b. Produces ATP.
c. Catabolic.

4. Glycogenesis
a. Synthesis of glycogen from glucose.
b. Uses ATP.
c. Anabolic.
 What I ate for Lunch:
(GLYCOLYSIS & GLYCOGENESIS)
Last week, I had a date with some of my college friends and we decided to eat
in an Italian restaurant. I ordered Spaghetti Aglio e Olio because I am a fan of oil
based pasta. They are just so delighting and good.

Spaghetti Aglio e Olio

Spaghetti Aglio e Olio is a kind of pasta dish that originated in Italy. Pasta is
made from durum or wheat, which is rich in carbohydrates. There are various types
of carbohydrates present in the pasta we eat, but the main ones are starches, sugars
such as glucose and fructose, as well as fiber. Pasta contains all of these different
carbohydrates in varying proportions. For eating this food, my body has to break
down the pasta in order to store the carbohydrates as energy.
 Breakdown of the starch:
All starches are broken down into single molecules of glucose in your gastrointestinal tract
during the digestion process. Starch molecules are too big to be absorbed.

In my mouth:

Amylase enzyme found in saliva would break down starch to maltose. -Amylase
would break down the (1-4)glycosidic bonds.

(Cummings, 2001)

(Science Learning, 2011)

In the stomach:

Stomach acid would deactivate the amylase and would stop starch digestion.
Salivary amylase would stop in the stomach due to the fall of pH to 3.0 due to the
gastric acid of produced in stomach.

(Cummings, 2001)

In the small intestine:

The maltose would then continue to the small intestine. Pancreatic juices would
contain pancreatic amylase enzymes, which are similar to salivary amylase. Maltase
enzyme would break down maltose to 2 molecules of glucose. Glucose is then
absorbed by the villi of the intestine to be transported in the bloodstream.

(Cummings, 2001)
 MALTASE

(Science Learning, 2011)

While glucose in the bloodstream can reach all body cells, it can't enter them.
Entering cells requires crossing a cell membrane, which glucose can't do on its own.
Glucose from the bloodstream enters cells with the help of two proteins. The first is
called glucose transporter, or GLUT protein. The second is the hormone insulin,
which the pancreas releases into the bloodstream to help cells absorb glucose from
the blood.

(Science Learning, 2011)

Once inside the cell, glycolysis would then occur in the cytoplasm in order to
metabolize the glucose for energy storage. Glycolysis is done in order to metabolize
the carbohydrates for ATP generation for our body.
 Start of Glycolysis:

(Shmoop Editorial Team, 2008)

Glycolysis is a process to breakdown of glucose to simpler molecules by

releasing energy in every cell. Intermediate products formed for other metabolic
pathways. Glycolysis occur inside cytoplasm.

Phase 1: The Priming Step

 The first phase of Glycolysis requires an input of energy in the form of ATP.
Glucose is phosphorolated at the 6 carbon by ATP via the enzyme Hexokinase to
yield Glucose-6-phosphate (G-6-P). This is a regulatory step which is negatively
regulated by the presence of glucose-6-phosphate. Glucose-6-phosphate is then
converted into Fructose-6-phosphate (F-6-P) by Phosphoglucoisomerase.

Fructose-6-phosphate is once again phosphorolated this time at the 1 carbon

position by ATP via the enzyme Phosphofructokinase to yield Fructose-1,6-
bisphosphate (FBP). This is the committed step of glycolysis because of its large
energy value. Fructose-1,6-bisphosphate is then cleaved into two, three carbon
molecules; Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde-3-phosphate
(G-3-P) by the enzyme Fructose bisphosphate aldolase.

Because the next portion of Glycolysis requires the molecule Glyceraldehyde-

3-phosphate to continue Dihydroxyacetone phosphate is converted into D-
Glyceraldehyde-3-phosphate by the enzyme Triose phosphate isomerase.

Phase 2: The Pay Off Step

The second phase of Glycolysis where 4 molecules of ATP are produced per
molecule of glucose. Glyceraldehyde-3-phosphate is phosphorolated at the 1 carbon
by the enzyme Glyceraldehyde-3-phosphate dehodrogenase to yield the high energy
molecule 1,3-Bisphosphoglycerate (BPG). ADP is then phosphorolated at the
expense of 1,3-Bisphosphoglycerate by the enzyme Phosphoglycerate kinase to
yield ATP and 3-Phosphoglycerate (3-PG)

3-Phosphoglycerate is then converted into 2-Phosphoglycerate by

Phosphoglycerate mutase in preparation to yield another high energy molecule 2-
Phosphoglycerate is then converted to phosphoenolpyruvate (PEP) by Enolase.
H2O, potassium, and magnesium are all released as a result. ADP is once again
phosphorolated, this time at the expense of PEP by the enzyme pyruvate kinase to
yield another molecule of ATP and and pyruvate. This step is regulated by the
energy in the cell. The higher the energy of the cell the more inhibited pyruvate
kinase becomes. Indicators of high energy levels within the cell are high
concentrations of ATP, Acetyl-CoA, Alanine, and cAMP.

Because Glucose is split to yield two molecules of D-Glyceraldehyde-3-

phosphate, each step in the "Pay Off" phase occurs twice per molecule of glucose.

1 molecule of glucose would produce 2 molecules of pyruvate. In an

anaerobic condition, pyruvate would be converted to lactate via lactate
dehydrogenase. Lactate process is needed in order to recycle the NAD+ used in the
glycolysis process since it is only limited. While in an aerobic condition, pyruvate
would be converted to acetyl coA via pyruvate dehydrogenase. It would then
proceed to Citric Acid Cycle and Oxidative Phosphorylation for more gain of ATP.
Total ATP produced in glycolysis would be 4 ATP, but since 2 ATP was utilized, only
2 ATP per molecule of glucose is produced. With one glucose will yield net product
of 2 pyruvate, 2 NADH and 2 ATP.

Pyruvate is the end product in glycolysis. Under aerobic condition, pyruvate

is oxidized to form acety-CoA which enter Krebs cycle in mitochondria. Adequate
oxygen is required to oxidize the NADH and FADH2 formed. Thus, it is called aerobic
glycolysis. Meanwhile, pyruvate is converted to lactate under anaerobic condition.
 Citric Acid Cycle/Krebs Cycle:

(Diwan, 2007)

Citric acid cycle is done in the site of mitochondria and is different from
glycolysis in which it is a cyclic pathway while the latter is a linear pathway.
Oxaloacetate along with acetyl coA will be converted to citrate via citrate synthase.
The pathway will go on producing 3 molecules of NADH (via isocitrate
dehydrogenase, ketoglutarate dehydrogenase, and malate dehydrogenase), 1
molecule of FADH (via succinate dehydrogenase) , and 1 GTP(via succinyl coA
synthetase). The ATP produced here was only thru substrate level phosphorylation.

In the first step of the citric acid cycle, acetyl CoA joins with a four-carbon
molecule, oxaloacetate, releasing the CoA group and forming a six-carbon molecule
called citrate. In the second step, citrate is converted into its isomer, isocitrate. This
is actually a two-step process, involving first the removal and then the addition of a
water molecule. In the third step, isocitrate is oxidized and releases a molecule of
carbon dioxide, leaving behind a five-carbon molecule (-ketoglutarate). During this
step, NAD+ is reduced to form NADH. The enzyme catalyzing this step, isocitrate
dehydrogenase, is important in regulating the speed of the citric acid cycle. The
fourth step is similar to the third. In this case, its -ketoglutarate thats oxidized,
reducing NAD+ to NADH and releasing a molecule of carbon dioxide in the process.
The remaining four-carbon molecule picks up Coenzyme A, forming the unstable
compound succinyl CoA. The enzyme catalyzing this step, -ketoglutarate
dehydrogenase, is also important in regulation of the citric acid cycle. In step five,
the CoA of succinyl CoA is replaced by a phosphate group, which is then transferred
to ADP to make ATP. In some cells, GDP (guanine diphosphate) is used instead of
ADP, forming GTP (guanine triphosphate) as a product. The four-carbon molecule
produced in this step is called succinate.

Succinate is oxidized, forming another four-carbon molecule called fumarate.

In this reaction, two hydrogen atoms (with their electrons) are transferred to FAD,
producing FADH2.The enzyme that carries out this step is embedded in the inner
membrane of the mitochondrion, so FADH2 can transfer its electrons directly into
the electron transport chain. Water is added to the four-carbon molecule fumarate,
converting it into another four-carbon molecule called malate. In the last step of the
citric acid cycle, oxaloacetate is regenerated by oxidation of malate. Another
molecule of NAD+ is reduced to NADH in the process.

Overall, one turn of the citric acid cycle releases two carbon dioxide
molecules and produces three NADH, one FADH2, and one ATP or GTP. The citric
acid cycle goes around twice for each molecule of glucose that enters cellular
respiration, because there are two pyruvates made per glucose.
 Start of Glycogenesis:

(Check Diabetes Organization, 2014)

Glycogenesis is an important metabolic activity in which molecules of glucose

in the body is converted to glycogen in order to be stored in the liver etc. In theory,
it is defined as a process in which glucose molecules are added to glycogen chains.
Glycogenesis is activated when the body is in a state of rest or during high glucose
level in the blood (due to high carbohydrate diet or due to diabetes) thus making
insulin activate this process to reduce blood sugar level. However the synthesis of
glycogen largely depends on the energy and glucose levels in the body.

If the body has adequate amount of ATP for its need, some glucose would be
converted to glycogen for long term energy storage. Glucose is converted to
glycogen by converting it first to glucose-6-phosphate via hexokinase using ATP. It
would then be converted to glucose-1-phosphate via phosphoglucomutase.
Glycogen synthase would start connecting the glucose-1-phosphate via the (1-4)
glycosidic bond, and branching enzyme would connect long chains of it via (1-6)
glycosidic bond.

The first step involves synthesis of UDP-glucose from glucose-1-phosphate

when catalyzed by UDP-glucose pyrophosphorylase. The water present in this
reaction gives way to hydrolysis process, which converts pyrophosphate to
orthophosphate thus making this first step a non-reversible reaction.

The UDP-glucose thus produced is catalyzed by glycogen synthase in which it

gets attached to the hydroxyl group forming -1,4-glycosidic link. This binding
requires a protein like glycogenin, which contains the glycogen branching enzyme.
Inhibitors of Glycolysis:
1. Sulfhydryl agents and alkylating agents.
- Inhibits formation of a thiohemiacetal

2. Hyperglycemia
- Non-formation of thiohemiacetal

3. Arsenate
- Prevent net synthesis of ATP without inhibiting glycolysis.

4. Fluoride
- Inhibits enzyme enolase.

Inhibitors of Cyclic Acid Cycle:

1. Fluorocitrate
- Inhibits action of aconitase.

2. Arsenite
- Inhibits

3. Malonate
- Have similar structure with succinate. Inhibit further production of succinate
dehydrogenase and thus inhibiting production of fumarate.
 Glycogen Storage Deficiency:

(Berg et al., 2012)

The underlying problem in all of the Glycogen Storage Diseases is the use and
storage of glycogen. Sometimes GSDs are also referred to as glycogenoses because
they are caused by difficulty in glycogen metabolism.

All of the Glycogen Storage Diseases are considered inherited metabolic

disorders. A metabolic disorder is a disease that disrupts metabolism. Therefore, a
person who has a metabolic disorder has a difficult time breaking down certain
foods and creating energy. A metabolic disease is most frequently caused by an
absence or deficiency in an enzyme (or protein). An enzyme can act to help the body
break down food into energy. There are many enzymes in the body and each act like
a machine on an assembly line. When one of the enzymes is not working properly,
the process of breaking down of specific foods can go more slowly or shut down
completely.

A person with a glycogen storage disease (GSD) has an absence or deficiency

of one of the enzymes responsible for making or breaking down glycogen in the
body. This is called an enzyme deficiency. The enzyme deficiency causes either
abnormal tissue concentrations of glycogen (too much or too little) or incorrectly or
abnormally formed glycogen (wrong shape). Depending on the type of GSD a person
has, their enzyme deficiency may be important in all parts of the body, or only in
some parts of the body, like the liver or muscle.
 During Biochem lecture:
(GLYCOGENOLYSIS &
GLUCONEOGENESIS)

During biochem lecture at 8am in the morning, my stomach would

grumble due to not eating breakfast most of the time. No glucose for energy for that
morning would mean that my body would have to rely to the stored glycogen in my
body. If glycogen was already depleted, my body would still have to find a different
source of carbon for glucose energy. Different substrate used would be amino acid,
glycerol, and proprionyl coA. Since brain needs glucose in order for it to work and in
order to be able to understand biochem topics as discussed by the doctors in class,
glycogenolysis and gluconeogenesis pathway would take over in order to produce
the much needed glucose energy for my brain.
 Start of Glycogenolysis:

(Ward, 2014)

Glycogenolysis is the biochemical breakdown of glycogen to glucose

whereas glycogenesis is the opposite, the formation of glycogen from glucose.
Glycogenolysis takes place in the cells of muscle and liver tissues in response to
hormonal and neural signals. In particular, glycogenolysis plays an important role in
the adrenaline-induced fight-or-flight response and the regulation of glucose levels
in the blood. The reverse process, glycogenesis, the formation of glycogen from
glucose, occurs in liver and muscle cells when glucose and ATP are present in
relatively high amounts.

Glycogen would be degraded to glucose-1-phosphate via glycogen

phosphorylase. This would release glucose-1-phosphate which would be converted
to glucose-6-phosphate via glucomutase. Glucose-6-phosphate can now go to
different pathways, one of which is glycolysis for generation of ATP needed for my
body. The (1-6) glycosidic bond in the glycogen would be phosphorylated by
debranching enzyme.

A tight regulation of glycogenolysis is needed to keep the blood sugar under

check. When the blood sugar and the energy levels are low, glycogenolysis comes
into play. Glucagon and epinephrine are the hormones which are secreted in low
blood sugar and when the body is in distress. These hormones act through an
intermediate molecule called cAMP which is necessary for the activation of Glycogen
phosphorylase. This mechanism is commonly found in liver.

In muscles, only epinephrine causes effective glycogenolysis and in muscles,

there is increased calcium inside the cells during muscle contraction . This also
results in activation of glycogen phosphorylase through a series of complicated
reactions which does not involve cAMP. Epinephrine is the hormone of fight, fright
and flight.

When there is excessive glucose or intermediates of glycolysis like glucose 6

phosphate or ATP, the energy currency, glycogenolysis is inhibited and the
metabolism is shifted towards glycolysis and Glycogenesis. Insulin, the anti
diabetogenic hormone inhibits glycogenolysis and prevents increase in blood sugar
level.
 Start of Gluconeogenesis:

(Diwan, 2007)

Gluconeogenesis is the metabolic process by which organisms produce

sugars for catabolic reactions from non-carbohydrate precursors. Glucose is the
only energy source used by the brain (with the exception of ketone bodies during
times of fasting), testes, erythrocytes, and kidney medulla. In mammals this process
occurs in the liver and kidneys.

The first step in gluconeogenesis is the conversion of pyruvate to

phosphoenolpyruvic acid (PEP). In order to convert pyruvate to PEP there are
several steps and several enzymes required. Pyruvate carboxylase, PEP
carboxykinase and malate dehydrogenase are the three enzymes responsible for
this conversion. Pyruvate carboxylase is found on the mitochondria and converts
pyruvate into oxaloacetate. Because oxaloacetate cannot pass through the
mitochondria membranes it must be first converted into malate by malate
dehydrogenase. Malate can then cross the mitochondria membrane into the
cytoplasm where it is then converted back into oxaloacetate with another malate
dehydrogenase. Lastly, oxaloacetate is converted into PEP via PEP carboxykinase.
The next several steps are exactly the same as glycolysis only the process is in
reverse. The second step that differs from glycolysis is the conversion of fructose-
1,6-bP to fructose-6-P with the use of the enzyme fructose-1,6-phosphatase. The
conversion of fructose-6-P to glucose-6-P uses the same enzyme as glycolysis,
phosphoglucoisomerase. The last step that differs from glycolysis is the conversion
of glucose-6-P to glucose with the enzyme glucose-6-phosphatase. This enzyme is
located in the endoplasmic reticulum.

Pyruvate would be converted back to glucose since my body would need

glucose for energy production. 2 ATP would be utilized via pyruvate carboxylase in
order to convert pyruvate to oxaloacetate. And 2 GTP would be used to convert
oxaloacetate by phosphoenolpyruvate (PEP). There is no direct conversion of
pyruvate to PEP. 2 ATP would also be used via the phosphoglycerate kinase. This
would result to a net of 6 ATP used via gluconeogenesis pathway.
 Importance of Carbohydrate Metabolism for A Medical Student

1. Chief source of energy needed for studying, especially for exams.

2. Storage of energy for more studying later as form of glycogen in muscles and
liver.
3. Contribute 60-70% total caloric percentage of the body.
4. Carbohydrate is the key intermediates of metabolism.
5. For biological cognition process of immunoglobulin.
6. Provide carbons for the synthesis of cell components.
7. Forms structural elements of the cell.
8. Needed for the central nervous system, the kidneys, the brain, the
muscles to function properly.
 Carbohydrate pun for the day:

Simple carbohydrates are sugars. All simple carbohydrates are made of just one or two
sugar molecules. They are the quickest source of energy, as they are very rapidly digested.

Complex carbohydrates may be referred to as dietary starch and are made of sugar
molecules strung together like a necklace or branched like a coil.
 Classification of Carbohydrates:

Carbohydrates can be classified in three different kinds. These would be

monosaccharide, disaccharide, and polysaccharide. Monosaccharides are simple
sugar molecules. These are the simplest kind of carbohydrates. Disaccharide is a
sugar composed of two monosaccharides. It is formed when two sugars are joined
together and a molecule of water is removed. These can be found from milk sugar
and cane sugar. Polysaccharides are composed of long chains of monosaccharide
units bound together by glycosidic linkages. They can have structures that can be
branched or linear. They can be found in most food like corn, potatoes, and grains.
Site for the different process related to carbohydrates in our body
as well as the net ATP produced per process:

(Boundless, 2016)

Glycolysis utilized 2 ATP for activation energy, but produced 4 ATP per
glucose molecule, so it produced a net of 2 ATP, 2 NADH, and 2 pyruvate.

In the citric acid cycle, there was 3 NADH produced per pyruvate molecule
(glucose have 2 pyruvate per glucose molecule), each having 5 ATP yield due
oxidative phosphorylation in the mitochondria, with malate aspartate shuttle as the
transport used. Malate aspartate would have 2.5 ATP/NADH molecule, while
Glycerol Phosphate shuttle would have 1.5 ATP/NADH molecule. FADH would yield
3 ATP molecules, while GTP would have 2 ATP molecules. NADH produced also in
pyruvate dehydrogenase would 5 ATP molecules. Glycolysis and citric acid total ATP
molecule produced would be 30-32 ATP.

(The Pennsylvania State University, 2016)

 Carbohydrate Metabolism Reflection of a Medical Student
Carbohydrate metabolism is important in our body. To further understand
how carbohydrate metabolism work, we first need to know how all the connected
different pathways converge for carbohydrates. Carbohydrates such as glucose,
fructose, and starch can be found in the different diets of an individual. Whether be
it complex sugar or simple sugar, people would have varying amount of
carbohydrates in their body due to their food preference and diet.

After eating a meal, glucose is used in glycolysis for breakdown in order to

make ATP as a fuel for cells. Glycogenesis is the process of glycogen synthesis when
too much glucose is flowing in the blood, and thus storage of energy would be
advantageous after eating a meal. When fasting, glycogenolysis is the pathway used
for breakdown of glycogen in order to produce ATP in absence of glucose. During
these times, gluconeogenesis is the metabolic pathway that is used due to lack of
glucose. It would result in the generation of glucose from non-carbohydrate carbon
substrates. Examples of these substrates would be pyruvate, lactate, glycerol, and
glucogenic amino acids.

It is amazing as to how the body could use up carbohydrates in order to run

the different processes in our body. Each organ has its own carbohydrate
requirements and energy needs, thus enabling the body for maintenance of
homeostasis. Especially for medical students like me, carbohydrate metabolism
would be very important for producing energy for studying in order to survive life
and med school as well. The brain needs glucose for it to work and we have to eat
carbohydrates in order to provide the requirements of the brain.

Though understanding the different pathways for carbohydrate metabolism

is very tough and hard to comprehend. It is needed in med school in order to know
the different effects of having and not having carbohydrate as a source of energy. It
could also help in recognizing various diseases linked to the pathway due to
deficient enzymes and such. Seeing a patient in the future having the same
symptoms with the disease related in carbohydrate metabolism would truly be
helpful for a medical doctor. We could treat the patients disease due to having
knowledge about the errors in the metabolic pathway causing that disease. I
appreciate carbohydrate metabolism now more than ever.

Though during my college years, I truly had no idea why we have to study
carbohydrate metabolism. I was very disinterested in the topic before, but now
wanting to be an excellent medical doctor, I have come to know that understanding
how carbohydrate metabolism works is a necessity in saving a life.