[CO8] Chemistry of Vision

Vitamin A has several functions in the does not fit as well into the protein, and
body. The most well known is its role in so a series of geometry changes in the
vision - hence carrots "make you able to protein begins. The resulting complex is
see in the dark". The retinol is oxidized referred to a bathrhodopsin.
to its aldehyde, retinal, which complexes
with a molecule in the eye called opsin. The retina is lined with many millions of
When a photon of light hits the complex, photoreceptor cells that consist of two
the retinal changes from the 11-cis form types: 7 million cones provide color
to the all-trans form, initiating a chain of information and sharpness of images,
events which results in the transmission and 120 million rods are extremely
of an impulse up the optic nerve. sensitive detectors of white light to
provide night vision. The tops of the rods
The molecule cis-retinal can absorb light and cones contain a region filled with
at a specific wavelength. When visible membrane-bound discs, which contain
light hits the cis-retinal, the cis-retinal the molecule cis-retinal bound to a
undergoes an isomerization, or change protein called opsin. The resulting
in molecular arrangement, to all-trans- complex is called rhodopsin or "visual
retinal. The new form of trans-retinal purple"

[CO9 .1] Citric Acid Cycle: Biological Effects of Disorders

Diseases of the tricarboxylic acid cycle The succinate dehydrogenase
(TCA cycle) with a pathway of citrate deficiency affects mitochondrial complex
cycle constitute a group of rare human II, which links the TCA cycle with the
diseases that affect core mitochondrial electron transport chain. The phenotype
metabolism. The Fumarase deficiency is is highly variable and can include Leigh
caused by impairment of the fumarate syndrome, leukodystrophy,
hydratase enzyme. cardiomyopathy and mental and motor
skill deterioration. The alpha-
The symptoms of the disorder include ketoglutarate dehydrogenase deficiency
developmental delay, severe mental is extremely rare and characterised by
retardation, language impairment, encephalopathy and hyperlactatemia
seizures and dysmorphic facial features. resulting in death in early childhood.

[CO9 .2] Pyruvate Decarboxytase: Health Implications of Deficiency

A boy with a hereditary defect of intermittent ataxia, often with

pyruvate decarboxylase has had choreoathetosis, following fever or
excitement, and lasting several days, Dexamethazone (Decadron) relieved
but is clinically normal between attacks. the attacks without affecting blood
There were excessive lipid droplets in pyruvate. Thiamine had little effect
his skeletal muscle. Blood, urine, and although attack frequency declined after
cerebrospinal fluid pyruvate levels were 19 months of treatment. This disorder, in
increased as were blood and urine which a constant metabolic defect
alanine levels but blood lactate levels predisposes to intermittent symptoms,
were rarely abnormal. Pyruvate levels may provide a model for understanding
tended to be higher during an attack, the relations between genetic and
and then, more abnormal (as were the environmental factors in other diseases.
clinical signs) in the late afternoon.

[CO10 .1] Essentials of Glucose Delivery: The Impact of Diabetes

Plasma glucose concentrations are glucose uptake to prevent
homeostatically regulated and hyperglycemia. Although the term
maintained within strict boundaries. homeostasis mostly refers to stable
Several mechanisms are in place to levels, the blood glucose concentrations
increase glucose output when glucose fluctuate over the day/night cycle, with
levels in the circulation drop as a result the highest concentrations occurring just
of glucose utilization, or to decrease prior to the activity period in anticipation
glucose output and increase tissue of increased caloric need.

Glucose that is not needed for energy is The plasma concentration of glucose is
stored in the form of glycogen as a controlled by a number of hormones, in
source of potential energy, readily particular, insulin and glucagon. The
available when needed. Most glycogen physiology of glucose homeostasis is
is stored in the liver and in muscle cells. controlled primarily by insulin release in
When these and other body cells are response to elevated glucose levels
saturated with glycogen, excess glucose (postprandial), although in birds,
is converted to fat and is stored as glucagon appears to serve as the
adipose tissue. primary regulator. Significant species
variations in glucose levels have been
noted.

[CO10 .2] Pentose Phosphate Pathway and Hemolytic Anemia Relationship

shown 30 years later to be caused by a
An antimalarial drug, pamaquine, was deficiency of glucose 6-phosphate
associated with the appearance of dehydrogenase, the enzyme catalyzing
severe and mysterious ailments. This the first step in the oxidative branch of
drug-induced hemolytic anemia was the pentose phosphate pathway. This
defect, which is inherited on the X sulfhydryl buffer that maintains the
chromosome, is the most common cysteine residues of hemoglobin and
enzymopathy. The major role of NADPH other red-blood-cell proteins in the
in red cells is to reduce the disulfide reduced state.
form of glutathione to the sulfhydryl
form. The enzyme that catalyzes the Therefore, Hemolytic anemia is caused
regeneration of reduced glutathione, the by the deficiency of certain enzymes of
the pentose phosphate pathway, the
principal enzyme involved is (A)
flavoprotein glutathione reductase, a Glucose-6-phosphate dehydrogenase
dimer of 50-kd subunits, is homologous (B) Aldolase (C) Fructose 1, 6-
to ferredoxin-NADP+ reductase. The bisphosphatase (D) Phosphohexose
reduced form of glutathione serves as a isomerase.

[CO10 .3] Glycogen Storage Disease and Affected Pathway

The primary anabolic and catabolic plasma membrane. Proposed pathways

pathways of glucose-6-phosphate in for glucose-6-phosphate metabolism in
gluconeogenic organs. G6Pase-α and neutrophils. Glucose transported into
G6PT are shown embedded within the the cytoplasm via GLUT1, the main
membrane of the endoplasmic glucose transporter in neutrophils, is
reticulum. GLUT2, the transporter metabolized by hexokinase to G6P,
responsible for the transport of glucose which can participate in glycolysis,
in and out of the cell in liver, kidney and hexose monophosphate shunt or
intestine, is shown embedded in the glycogen synthesis or can be
transported into the lumen of the
endoplasmic reticulum by G6PT.
Glycogen storage disease type I (GSD- originally categorized as GSD-I
I), also known as von Gierke disease, disorders,1,2 but most, if not all,
consists of a group of autosomal reported cases of GSD-Ic and GSD-Id
recessive disorders that occur with an have been genotyped and were shown
overall incidence of approximately 1 in to harbor the SLC37A4 mutations also
100,000 individuals.1,2 The subtype found in patients with GSD-Ib.9–12
GSD-Ia is caused by an inactivating G6PT deficiency is, therefore, implicated
mutation in the gene G6PC, which in all reported cases of GSD-Ib, GSD-Ic
encodes glucose-6-phosphatase-α and GSD-Id. This notion is consistent
(G6Pase-α),3,4 whereas the subtype with the biochemistry of the disease and
GSD-Ib results from an inactivating the finding that G6PT is a eukaryotic
mutation in SLC37A4,5,6 the gene that antiporter that transports glucose-6-
encodes a glucose-6-phosphate phosphate (G6P) into the lumen of the
transporter (G6PT).5–8 Two additional endoplasmic reticulum in exchange for
subtypes, GSD-Ic and GSD-Id, were inorganic phosphate.

[CO11] Carnitine: Fat Mover

Carnitine helps transport the fatty acids molecule of Pi by inorganic pyro

to the mitochondria to be burned as phosphatase. This reaction is highly
energy as same as fats being burned. In exergonic which drives the activation
the first step of the reaction, acyl-CoA reaction forward and makes it more
synthetase catalyzes the transfer of favorable. In the second step, the thiol
adenosine monophosphate group group of a cytosolic coenzyme A attacks
(AMP) from an ATP molecule onto the the acyl-adenylate, displacing AMP to
fatty acid generating a fatty acyl– form thioester fatty acyl-CoA.
adenylate intermediate and a In the second reaction, the activated
pyrophosphate group (PPi). The fatty acids that are intended for
pyrophosphate, formed from the mitochondrial oxidation are transported
hydrolysis of the two high-energy bonds into the matrix by a carrier protein, but
in ATP, is immediately hydrolyzed to two first the acyl-CoA must be transiently
attached to the hydroxyl group of moves into the matrix. In the third and
carnitine to form fatty acyl–carnitine. final reaction of the carnitine shuttle, the
This transesterification is catalyzed to fatty acyl group is transferred back from
carnitine acyltransferase 1 (also called fatty acyl-carnitine in the matrix to
carnitine palmitoyltransferase 1, CPT1). intramitochondrial coenzyme A
The fatty acyl–carnitine ester formed regenerating fatty acyl–CoA and a free
then diffuses across the intermembrane carnitine molecule. This reaction is
space of the mitochondria and enters catalyzed by carnitine acyltransferase 2
the matrix by passive transport through (also called CPT2), which is placed on
the acyl-carnitine/carnitine cotransporter the inner face of the inner mitochondrial
that is found in inner mitochondrial membrane. The carnitine molecule
membrane. This cotransporter return formed is then shuttled back into the
one molecule of carnitine from the intermembrane space by the same
matrix to the intermembrane space as cotransporter while the fatty acyl-CoA is
one molecule of fatty acyl– carnitine oxidized and used for ATP production.

REFERENCES:

https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_(
Biological_Chemistry)/Photoreceptors/Chemistry_of_Vision

Nelson, D. L., Cox, M. M., & Lehninger, A. L. (2017). Lehninger principles of

biochemistry (7th ed.). New York, NY: W.H. Freeman and Company.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178929/#!po=5.24194

https://www.ncbi.nlm.nih.gov/books/NBK22389/

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/glucose

https://jamanetwork.com/journals/jamaneurology/article-abstract/570951

Retrieved from: https://www.genome.jp/dbget-bin/www_bget?ds:H01022