5. MCFA, PUFA Prostaglandins And Compound Lipids Flashcards
Explain DHA
Fatty acids having 20 or more carbon atoms are called very long chain fatty acids (VLCFA). Eicosa penta-enoic acid (EPA) (C-20, 5 double bonds) and docosa hexa-enoic acid (DHA) (C-22, 6 double bonds) are good examples of VLCFA.
DHA is synthesized in liver from linolenic acid (Omega-3, C-18, 3 double bond). DHA is also available in large quantities in fish oils.
In human beings, DHA is accumulated in brain before birth and up to 12 weeks after birth. Outer segments of retinal rods contain high concentrations of DHA, which gives high fluidity to the membranes. This is required for the lateral and rotational movement of rhodopsin within the membrane during photo-activation.
DHA is especially required for the development of brain and retina. Low level of DHA in blood is seen in patients with retinitis pigmentosa.
Prostaglandins classification and functions
They are the most potent biologically active substances; as low as one nanogram/ml of PG will cause smooth muscle contraction.
Chemical Structure
All prostaglandins are considered to be derived from the 20 C cyclic saturated fatty acid, prostanoic acid.
Classification of Prostaglandins
According to the attachment of different substituent groups to the ring, PGs are named with capital letters such as A, B, E and F (Table 13.2). In the same series, depending on number of double bonds on the side chains they are denoted by a subscript after the capital letter, e.g. PGE1, PGE2, PGE3, etc. (Table 13.2).
1. Series1contains1doublebondat13–14(trans)
2. Series 2 have 2 double bonds at 13–14 (trans)
and 5–6 (cis). This is the most common variety.
3. Series3have3doublebonds,13–14(trans)5–
6 (cis) and 17–18 (cis).
The primary prostaglandins PGG and PGH, (the endoperoxides) are intermediates in the synthesis of others. Only 5 PGs are widely distributed in the body. They are PGD2, PGE2, PGF2 and PGI2 and thromboxane A2.
Biological Actions and Clinical Applications
1. Effects on CVS
Prostacyclin or PGI2 is synthesized by the vascular endothelium. Major effect is vasodilatation. It also inhibits platelet aggregation and has a protective effect on vessel wall against deposition of platelets. But any injury to the vessel wall would inhibit PGI2 synthesis so that platelet aggregation occurs to promote thrombus formation.
Thromboxane (TXA2) is the main PG produced by platelets. The major effects are vasoconstriction and platelet aggregation. Prostacyclin and thromboxane are opposing in activity (Table 13.3.). Prostaglandins lower the blood pressure.
2. Effects on Ovary and Uterus
PGF2 stimulates the uterine muscles. Hence PGF2 may be used for medical termination of pregnancy. Yet another use is in inducing labor and arresting postpartum hemorrhage. PGs are involved in LH induced ovulation. In cattle, if PG is given, luteolysis takes place and animal goes into estrus. Better fertilization rate is achieved with timely artificial insemination.
3. Effects on Respiratory Tract
PGF is a constrictor of bronchial smooth muscle; but PGE is a potent bronchodilator. PGE series are used in aerosols for relieving bronchospasm.
4. Effects on Immunity and Inflammation
PGE2 and D2 produce inflammation by increasing capillary permeability. Erythema and wheal are produced at the site of injury. The anti-infla- mmatory effect of PG synthesis inhibitor (aspirin; cortisol) is explained in Box 13.3. Moreover, PGE2 reduces both T and B cell functions. PGE2 is a sleep promoting substance.
5. Effects on Gastrointestinal Tract
PGs in general inhibit gastric secretion and increase intestinal motility. The inhibitory effect on gastric secretion is used therapeutically in treatment of acid peptic disease. But diarrhea may be an unwanted side effect.
6. Metabolic Effects
The metabolic effects may be through the action of hormones by the modulating effect on cAMP production. Prostaglandin E2 decreases lipolysis, increases calcium mobilization from bone and glycogen synthesis.
Lipid storage diseases and deficient enzymes
Fabrys disease - alpha galactosidase
Krabbes leukodystrophy - beta galactosidase
Pompes disease - alpha glucosidase
Gaucher’s disease - beta glucosidase
Tay Sachs disease - Hexosaminidase A
Niemann Pick disease - Sphingomyelinase
Metachromatic leukodystrophy - Sulfatide sulfatase
