BIOCHEM SGD: CHO METAB

CASE I
1. The Pyruvate Dehydrogenase enzyme of the PDC is most likely affected in the case
because it needs its coenzyme Thiamine Pyrophosphate (TPP) in order to do its action
(oxidative decarboxylation of pyruvate). Since there is low conc. of TPP, the pyruvate
dehydrogenase enzyme must be affected. Congenital Lactic Acidosis, as seen in the
case, is a disease caused by deficiency in pyruvate dehydrogenase. There is an
inability to convert pyruvate to Acetyl CoA that leads to pyruvate being converted to
lactic acid by the enzyme lactate dehydrogenase. This may lead to brain damage.
2. Pyruvate Dehydrogenase Complex (PDC) is composed of three different enzymes

3.

A. Since there is inability to convert pyruvate to Acetyl CoA, the brain uses pyruvate
oxidation and the TCA cycle as energy source leading to neurologic involvement.
B. There is increase pyruvate because it cant be oxidatively decarboxylized due to the
lack/affected pyruvate dehydrogenase enzyme. The increased lactate is seen because
the accumulated pyruvate is converted to lactate by the enzyme lactate dehydrogenase.
There is increased in alanine because pyruvate can also be converted to alanine by
transamination with alpha-ketoglutarate (NOT SURE ABOUT ALANINE)
4. A. Ketogenic Diet- the main treatment for PDCD currently. The diet is high fat, low
protein and low carbohydrate. The diet forces the body to create ketones to use as
energy, instead of glucose. The ketones are then used to fuel the brain and body. The
diet is initiated under a doctors supervision and is tailored to your childs specific needs.
The diet can be initiated under a 4:1, 3:1, or a 2:1 ratio. This means, for example, four
parts of fat to a combined one part protein and carbohydrate.

B. Thiamine sufficient thiamine is needed for pyruvate dehydrogenase to function as it

acts as a coenzyme.
C. Dichloroacetate reduces the inhibitory phosphorylation of pyruvate dehydrogenase
complex. Resolution of lactic acidosis is observed in patients with E1 alpha enzyme
subunit mutations that reduce enzyme stability. (not sure me here mga beshies hahaha)

CASE II
1. Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency,
is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the
survival of red blood cells. Both autosomal dominant and recessive inheritance have
been observed with the disorder; classically, and more commonly, the inheritance
is autosomal recessive. Pyruvate kinase deficiency is the second most common
cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.
2. The enzyme glucose-6-phosphate dehydrogenase (G6PD) is one of the enzymes
of the pentose phosphate pathway. This pathway is involved in keeping an adequate
amount of the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) in
cells. NADPH in turn maintains the levels of glutathione, which protects the red cell
from oxidative damage. G6PD is the rate-limiting enzyme in the pentose phosphate
pathway. Thus, deficiency of the G6PD enzyme results in reduced glutathione
making the red cells vulnerable to oxidative damage and thus liable to hemolysis.
G6PD reduces NADP+ to NADPH while oxidizing glucose-6-phosphate.
3. Carriers of the underlying mutation do not show any symptoms unless their red
blood cells are exposed to certain triggers, which can be of three main types:

foods (fava beans is one of them),

medicines and other chemicals
stress from a bacterial or viral infection

Many substances are potentially harmful to people with G6PD deficiency. Variation in
response to these substances makes individual predictions difficult. Antimalarial
drugs that can cause acute hemolysis in people with G6PD deficiency
include primaquine, pamaquine, and chloroquine. There is evidence that other
antimalarials may also exacerbate G6PD deficiency, but only at higher
doses. Sulfonamides (such as sulfanilamide, sulfamethoxazole, andmafenide),
thiazolesulfone, methylene blue, and naphthalene should also be avoided by people
with G6PD deficiency as they antagonize folate synthesis, as should

certain analgesics (such as aspirin, phenazopyridine, and acetanilide) and a few

non-sulfa antibiotics (nalidixic acid, nitrofurantoin,isoniazid, dapsone,
and furazolidone). Henna has been known to cause hemolytic crisis in G6PDdeficient infants. Rasburicase is also contraindicated in G6PD deficiency.
4.

5. Most individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency do not

need treatment. The main treatment for G6PD deficiency is avoidance of oxidative
stressors. Identification and discontinuation of the precipitating agent is critical to
manage hemolysis in patients with G6PD deficiency. Rarely, anemia may be severe
enough to warrant a blood transfusion. Recognizing that hemolysis is self-limited
and often resolves in 8 to 14 days. Splenectomy generally is not recommended.
Folic acid and iron potentially are useful in hemolysis, although G6PD deficiency
usually is asymptomatic and the associated hemolysis usually is short-lived. Patients
with chronic hemolysis or non-spherocytic anemia should be placed on daily folic
acid supplements. Antioxidants such as vitamin E and selenium have no proven
benefit for the treatment of G6PD deficiency.
The prognosis for a person with G6PD is very good. They typically have no
symptoms and can live a normal lifespan with a normal quality of life. In rare cases,
episodes of hemolytic anemia can be fatal. Normally people with G6PD who have
episodes of hemolytic anemia recover quickly with minimal treatment.

CASE III
1. Glycogen Storage Disease (GSD) Type III is also known as Cori Disease. There is a
deficiency of Amylo-1,6-glucosidase or debranching enzyme, the enzyme responsible
for hydrolyzing the alpha-1,6-linkage of the remaining single glucosyl residue in the
process of debranching glycogen. There is increased amount of glycogen with an
abnormal structure (short outer branch) in the affected organs (muscle and liver)
2.
3. People with GSD III often have short growth because of their liver problems, which
can lead to short stature. Since the liver is one of the affected organs of GSD III,
enlargement of the liver or hepatomegaly is usually seen. The skeletal muscle is also
affected by GSD III leading to hypotonic and flaccid extremities.
4. To prevent hypoglycemia, patients with GSD must carefully follow certain special diets.
Frequent high carbohydrate meals during the day can help blood sugar levels from
dropping. In some children with GSD, continuous nighttime feeding is observed wherein
a special feeding tubed is placed into their stomach to give formula with a high
concentration of glucose.

CASE IV
1. There is decreased PFK-2 and an increased Fructose BP-2 during fasting because to
make way for gluconeogenesis to occur. PFK-2 (I FORGOT WHAT THIS ENZYME
DOES). Fructose BP-2 inactivates PFK-1, the rate-limiting step in glycolysis, and
activates Fructose 1,6-BP, the enzyme responsible for converting Fructose 1,6-BP to
Glucose-6-P in gluconeogenesis, the process of converting noncarbohydrate precursors
to synthesize energy (glucose).
2. Pyruvate kinase, the enzyme responsible for converting Phosphoenolpyruvate (PEP)
to Pyruvate, is inhibited during fasting to ensure that gluconeogenesis occurs. The
substrate PEP is channeled to gluconeogenesis during fasting since there is demand to
make glucose since blood glucose is low.