PPP Flashcards
What is the major site of production of the superoxide ion?
mitochondrial ETC
What type of agent is H2O2? Where are its major sources of production?
weak oxidizing agent - lysis cell membranes
oxidases, oxygenases, peroxidases
What are the major sources of OHo and Oo?
high energy ionizing radiation
What promotes to production of ROS in RBC?
heme group
What are the enzymatic antioxidants found in the body?
glutathione peroxidase
superoxide dismutase
catalase
What is the important antioxidant that is present in all cells but especially in RBC?
glutathione
Glutathione is composed of what 3 aminoacids?
gamma glutamic acid
cysteine
glycine
Which form of glutathione is a monomer & which form is a dimer?
monomer: reduced
dimer: oxidized
How does the PPP play a role in providing antioxidants?
provides the NADPH that is required to reduce glutatione disulphide (GSSG)
How is H2O2 converted to 2H2O in RBC?
In a reaction catalyzed by glutathione peroxidase, reduced glutathione (G-SH) is used to reduce H2O2 into 2H2O, which also produces the oxidized glutathione (G-S-S-G)
What is provided by the oxidative branch of the PPP?
NADPH
What is provided by the non-oxidative branch of the PPP?
pentose- (nucleotides & nucleic acid)
glycolytic intermediates
Where is the PPP active?
liver, adipose tissue, adrenal cortex, erythrocytes, thyroid, skeletal muscle
What are the steps in the oxidative branch of the PPP?
- glucose-6-phosphate → 6-phosphogluconolactone
- glucose-6-phosphate dehydrogenase
- NADP+ → NADPH
- 6-phosphogluconolactone → 6-phosphogluconate
- lactonase
- + H2O
- 6-phosphogluconate → ribulose-5-phosphate
- 6-phosphogluconate dehydrogenase
- NADP+ → NADPH
What are the steps in the non-oxidative branch of the PPP?
What is the first step in the non-oxidative stage of the PPP?
- Ribulose-5-phosphate → Ribose-5-phosphate (intermediate for other PPP reactions)
- phosphopentose isomerase
- Ribulose-5-phosphate → Xylulose-5-phosphate
- Phosphopentose epimerase
What is the first transketolase reaction in the non-oxidative stage of the PPP?
- Xylulose-5-phosphate + ribose-5-phosphate → glyceraldehyde-3-phosphate + sedoheptulose-7-phosphate
- transketolase (transfers 2 carbon unit)
- TPP
In the first transketolase reaction, the donating & accepting sugars are always in what forms?
donating: ketose
accepting: aldose
What reaction in the non-oxidative stage of the PPP comes after the first transketolase reaction?
Transaldolase reaction
What are the steps in the transaldolase reaction of the non-oxidative stage of the PPP?
- glyceraldehyde-3-phosphate + sedoheptulose-7-phosphate → erythrose-4-phosphate + fructose-6-phosphate
- transaldolase (transfers 3 carbon unit)
In the transaldolase reaction of the non-oxidizing stage of the PPP, the donating & accepting sugars are always in what forms?
donating: ketose
accepting: aldose
What reaction in the non-oxidative stage of the PPP comes after transaldolase reaction?
second transketolase reaction
What are the steps of the second transketolase reaction of the non-oxidizing stage of the PPP?
- xylulose-5-phosphate + erythrose-4-phosphate → glyceraldehyde-3-phosphate + fructose-6-phosphate
- transketolase
What happens to excess ribose-5-phosphate produced from the pPP?
quantitatively converted to glycolytic intermediate
The oxidative branch of the PPP is controlled by what the concentration of what molecule?
What is the rate limiting enzyme of the oxidative branch of the PPP?
Is the oxidative branch of the PPP reversible?
[NADPH]
G-6-PD is RL enzyme (inhibited by NADPH)
no, it is not reversible
How can the non-oxidative branch of the PPP change based on the availability of certain substrates?
Reversible - common intermediates with glycolysis allow it to operate in different modes depending on the need for NADPH and/or ribose
G-6-PDH deficiency is what type of germline mutation?
X-linked
What adverse events can occur in an individual with G-6-PDH deficiency?
condition affects RBC
oxidant induced hemolytic anemia - (quinones & fava beans)
The uronic pathway in the liver catalyzes what reactions?
It produces what additional product in other organisms, but NOT humans?
glucose to glucuronic acid & pentoses
produces ascorbic acid in other organisms - but NOT in humans (we need to acquire it from our diet)
What are the functions of glucuronate?
(need UDP to activate)
add chargers to materials to increase their solubility in aqueous solutions
Also, part of GAGs & glycoproteins
Describe the steps involved with glucuronate synthesis.
- UDP-glucose → UDP-glucuronate
- UDP-glucose dehydrogenase
- 2NAD+ → NADPH
- UPD-glucuronate → glucuronate
- UDP-glucuronosyl transferases (connect various substrates to anomeric carbon)
Other than glucuronate synthesis, how else can the body acquire glucuronate?
diet or inositol degradation
What are the 6 examples of compound that are degraded & excreted as urinary glucuronides?
- estrogen
- progesterone
- triiodothyronine
- acetylaminofluorene
- meprobamate
- morphine
How is bilirubin altered in preparation for excretion?
glucuronate is added to each of its 2 carboxyl groups for solubility & excretion
Conjugated bilirubin is measured by what lab test?
Unconjugated?
Conjugated: direct
Unconjugated: indirect