Ch 23 biochemistry

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Questions and Answers

What is the primary function of thromboxane (TXA 2) in the vascular system?

Vasoconstriction (correct)

Vasodilation

Increasing capillary permeability

Decreasing platelet aggregation

Which prostaglandin is primarily responsible for promoting sleep?

PGF 2α

PGE 2

TXA 2

PGD2 (correct)

How do prostaglandins affect cAMP levels in renal tubule cells?

They reduce cAMP levels (correct)

They increase cAMP levels

They do not affect cAMP levels

They stabilize cAMP levels

Which effect is NOT associated with PGF 2α in the gastrointestinal tract?

Relaxes circular muscle Signup and view all the answers

What primary effect does PGE 2 have when administered into the posterior hypothalamus?

Causes wakefulness Signup and view all the answers

What role do cysteinyl leukotrienes play in respiratory function?

They stimulate mucus secretion Signup and view all the answers

Which prostaglandins are predominantly associated with promoting inflammation?

PGE 2 and PGI 2 Signup and view all the answers

What effect does high concentration of PGE 2 have on uterine muscle?

Causes relaxation Signup and view all the answers

Which of the following statements about TXA 2 is TRUE?

It promotes smooth muscle cell proliferation. Signup and view all the answers

What role do leukotrienes C4, D4, and E4 play in the respiratory system?

They constrict bronchial airway musculature Signup and view all the answers

Which of the following statements regarding the effects of PGE compounds is correct?

PGE compounds enhance leukocyte infiltration during inflammation. Signup and view all the answers

What is one of the key roles of PGF 2α in female reproductive physiology?

Essential for onset of parturition Signup and view all the answers

What impact does aspirin have on the synthesis and release of PGE 2?

It blocks synthesis and release. Signup and view all the answers

What is the primary function of leukotrienes in the body?

They are involved in inflammatory responses. Signup and view all the answers

Which enzyme is specifically responsible for the formation of leukotrienes?

5-lipoxygenase Signup and view all the answers

Which eicosanoid is primarily involved in enhancing penile erection by relaxing smooth muscle?

PGE 1 Signup and view all the answers

What symptoms are associated with essential fatty acid deficiency in humans?

Skin lesions and lipid impairment Signup and view all the answers

What effect do NSAIDs have on norepinephrine release in vivo?

They increase norepinephrine release. Signup and view all the answers

What is the role of endogenous pyrogens in the synthesis of PGE 2?

They promote the synthesis and release of PGE 2. Signup and view all the answers

In response to what types of stimuli do leukotrienes get formed?

Both immunologic and nonimmunologic stimuli Signup and view all the answers

What modifications in the diet are recommended to reduce the risk of coronary heart disease?

Increased polyunsaturated fatty acids Signup and view all the answers

Which of the following diseases is associated with abnormal metabolism of essential fatty acids?

Cystic fibrosis Signup and view all the answers

What is the effect of blocking lipoxygenase action with sulfasalazine or indomethacin?

Prolongs half-life of prostaglandins Signup and view all the answers

What roles do lipoxins play in the body?

They are involved in the resolution of inflammation. Signup and view all the answers

Study Notes

Biosynthesis of Fatty Acids & Eicosanoids

Fatty acids are synthesized by an extramitochondrial system in the cytosol, forming palmitate from acetyl-CoA.
In most mammals, glucose is the primary substrate for lipogenesis; in ruminants, acetate is more prevalent.
Critical diseases of the fatty acid pathway synthesis have not been reported in humans.
Inhibition of lipogenesis occurs in type 1 diabetes mellitus, and variations in its activity affect obesity.
Unsaturated fatty acids in phospholipids maintain cell membrane fluidity.
A high polyunsaturated fatty acid to saturated fatty acid ratio (P:S ratio) benefits coronary heart disease prevention.
Animal cells have limited fatty acid desaturation capacity, requiring dietary polyunsaturated fatty acids from plants.
Essential fatty acids (EFAs) produce eicosanoids—prostaglandins, thromboxanes, leukotrienes, and lipoxins.
Prostaglandins regulate inflammatory responses, pain, sleep, blood clotting, and reproduction.
Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting prostaglandin synthesis.
Leukotrienes affect muscle contractions and attract immune cells (chemotaxis), contributing to inflammation and allergic reactions.
Lipoxins also play roles in inflammation.

The Main Pathway for De Novo Synthesis of Fatty Acids (Lipogenesis)

Fatty acid synthesis primarily occurs in the cytosol.
The cofactors for this process include NADPH, ATP, manganese, biotin, and bicarbonate.
Acetyl-CoA is the direct precursor, and the final product is palmitate.

Production of Malonyl-CoA

Bicarbonate is required and acetyl-CoA carboxylase is present.
This complex enzyme is a multienzyme protein, containing biotin, biotin carboxyl carrier protein, biotin carboxylase, and carboxyl transferase.
The enzyme has a regulatory allosteric site and its function is critical to regulating fatty acid synthesis.
The reaction occurs in two steps: carboxylation of biotin and transfer of the carboxyl group to acetyl-CoA.

The Fatty Acid Synthase Complex

The synthase complex contains 6 enzymes and is a homodimer with two identical subunits.
Its structure is arranged in an X shape, potentially close to the 3-ketoacyl reductase enzyme domain.
The complex's function involves combining malonyl-CoA with an initiating acetyl-CoA molecule to gradually extend the fatty acid chain.
The complex utilizes pantothenic acid in the form of 4'-phosphopantetheine.

Fatty Acid Synthesis in the Mitochondria

Acetyl CoA is the main building block formed from glucose via pyruvate oxidation in the mitochondria.
Acetyl CoA is not readily diffusible across the mitochondrial membranes, necessitating a dedicated transport mechanism—using citrate.
Citrate, produced by combining acetyl CoA with oxaloacetate, is carried into the cytosol then converted to acetyl CoA and oxaloacetate.
NADPH is needed, supplied by the pentose phosphate pathway (it's hydrogen is used in the reductive synthesis of fatty acids)
Alternative sources of NADPH for lipogenesis include reactions of malate to pyruvate catalyzed by "malic enzyme" and the isocitrate dehydrogenase reaction.
Ruminants rely more on acetate as a precursor for lipogenesis via the extramitochondrial pathway.

Elongation of Fatty Acid Chains

The microsomal system elongates saturated and unsaturated acyl-CoAs with from 10 to more carbon atoms.
This process uses malonyl-CoA as an acetyl donor with NADPH as the reducing equivalent.
The microsomal fatty acid elongases are responsible for this pathway.

Nutritional Control of Lipogenesis

Lipogenesis rate is high in well-fed animals due to a higher carbohydrate intake.
Depressed by calorie restrictions, high-fat diets, and insulin deficiency like in diabetes mellitus.
An inverse relationship between hepatic lipogenesis and circulating free fatty acids.
Lipogenesis is elevated when glucose is replaced in the diet with sucrose due to the fructose bypassing the key regulatory point in glycolysis.
Regulating mechanisms are short-term (allosteric and covalent modifications of enzymes) or long term (gene expression).
Acetyl-CoA carboxylase is the most important regulatory enzyme for lipogenesis, activated by citrate.
Pyruvate dehydrogenase is also regulated by acyl-CoA, leading increased intramitochondrial ATP/ADP ratios and inactivation of the enzyme.
Insulin increases glucose transport into cells, enabling more pyruvate and glycerol-3-phosphate for fatty acid synthesis and activation of pyruvate dehydrogenase.

Essential Fatty Acid Deficiency and Eicosanoids

Deficiency symptoms occur when EFAs are missing from the diet, particularly in rats fed purified nonlipid diets.
Deficiency may be cured by including EFAs such as linoleic, alpha-linolenic, and arachidonic acids.
EFAs are concentrated in vegetable oils and present in animal carcasses (though in lower quantities).
They are part of the structure of phospholipids in the cell and mitochondrial membranes.
EFAs are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation.

Clinical Aspects

Symptoms of essential fatty acid deficiency in humans may include skin lesions and/or impaired lipid transport.
Abnormal essential fatty acid metabolism occurs in various diseases, often connected to dietary deficiencies.
Very-long-chain polyunsaturated fatty acids are elevated in some brain diseases such as Zellweger syndrome.
High P:S ratios of diests correlate with lower cholesterol levels and reduced risk for coronary heart disease.
Trans fatty acid intake has potential negative consequences on health affecting various disorders.
Specific aspects of prostaglandins, thromboxanes, leukotrienes, and lipoxins play key roles in the CNS, inflammation, immune response, reproductive processes, and the cardiovascular system.

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