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Biochemistry

The Effects of Enzyme Inhibitors

Enzymes can be inhibited

  • competitively, when the substrate and inhibitor compete for binding to the same active site or
  • noncompetitively, when the inhibitor binds somewhere else on the enzyme molecule reducing its efficiency.

The distinction can be determined by plotting enzyme activity with and without the inhibitor present.

Competitive Inhibition

In the presence of a competitive inhibitor, it takes a higher substrate concentration to achieve the same velocities that were reached in its absence. So while Vmax can still be reached if sufficient substrate is available, one-half Vmax requires a higher [S] than before and thus Km is larger.

Noncompetitive Inhibition

With noncompetitive inhibition, enzyme molecules that have been bound by the inhibitor are taken out

  • enzyme rate (velocity) is reduced for all values of [S], including
  • Vmax and one-half Vmax but
  • Km remains unchanged because the active site of those enzyme molecules that have not been inhibited is unchanged.

Thyroid Hormones

Thyroid hormones (T4 and T3) are tyrosine-based hormones produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland, are primarily responsible for regulation of metabolism. Iodine is necessary for the production of T3 (triiodothyronine) and T4 (thyroxine).

A deficiency of iodine leads to decreased production of T3 and T4, enlarges  the thyroid tissue and will cause the disease known as goitre.

Thyroid hormones are transported by Thyroid-Binding Globulin

Thyroxine binding globulin (TBG), a glycoprotein binds T4 and T3 and has the capacity to bind 20 μg/dL of plasma.

Diseases

1. Hyperthyroidism (an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.

2 Hypothyroidism (an example is Hashimoto’s thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.

Folate: Folic Acid, Folacin Folate, also known as folic acid or folacin, aids in protein metabolism, promoting red blood cell formation, and lowering the risk for neural tube birth defects. Folate may also play a role in controlling homocysteine levels, thus reducing the risk for coronary heart disease.

RDA for folate is 400 mcg/day for adult males and females. Pregnancy will increase the RDA for folate to 600 mcg/day.

Folate Deficiency

Folate deficiency affects cell growth and protein production, which can lead to overall impaired growth. Deficiency symptoms also include anemia and diarrhea.

A folate deficiency in women who are pregnant or of child bearing age may result in the delivery of a baby with neural tube defects such as spina bifida.

Keq, Kw and pH

As H2O is the medium of biological systems one must consider the role of this molecule in the dissociation of ions from biological molecules. Water is essentially a neutral molecule but will ionize to a small degree. This can be described by a simple equilibrium equation:

H2O <-------> H+ + OH-

This equilibrium can be calculated as for any reaction:

Keq = [H+][OH-]/[H2O]

Since the concentration of H2O is very high (55.5M) relative to that of the [H+] and [OH-], consideration of it is generally removed from the equation by multiplying both sides by 55.5 yielding a new term, Kw:

Kw = [H+][OH-]

This term is referred to as the ion product. In pure water, to which no acids or bases have been added:

Kw = 1 x 10-14 M2

As Kw is constant, if one considers the case of pure water to which no acids or bases have been added:

[H+] = [OH-] = 1 x 10-7 M

This term can be reduced to reflect the hydrogen ion concentration of any solution. This is termed the pH, where:

pH = -log[H+]

The Protein Buffer Systems

The protein buffers are very important in the plasma and the intracellular fluids but their concentration is very low in cerebrospinal fluid, lymph and interstitial fluids.

The proteins exist as anions serving as conjugate bases (Pr ) at the blood pH 7.4 and form conjugate acids (HPr) accepting H+ .  They have the capacity to buffer some H2CO3  in the blood.

Cori Cycle

The Cori Cycle operates during exercise, when aerobic metabolism in muscle cannot keep up with energy needs.

For a brief burst of ATP utilization, muscle cells utilize ~P stored as phosphocreatine. For more extended exercise, ATP is mainly provided by Glycolysis.

Lactate, produced from pyruvate, passes via the blood to the liver where it is converted to glucose. The glucose may travel back to the muscle to fuel Glycolysis.

The Cori Cycle costs 6 P in liver for every 2P made available in muscle. The net cost is 4 P Although costly in terms of "high energy" bonds, the Cori Cycle allows the organism to accommodate to large fluctuations in energy needs of skeletal muscle between rest and exercise.

COENZYMES

 Enzymes may be simple proteins, or complex enzymes.

A complex enzyme contains a non-protein part, called as prosthetic group (co-enzymes).

Coenzymes are heat stable low molecular weight organic compound. The combined form of protein and the co-enzyme are called as holo-enzyme. The heat labile or unstable part of the holo-enzyme is called as apo-enzyme. The apo-enzyme gives necessary three dimensional structures required for the enzymatic chemical reaction.

Co-enzymes are very essential for the biological activities of the enzyme.

Co-enzymes combine loosely with apo-enzyme and are released easily by dialysis. Most of the co-enzymes are derivatives of vitamin B complex

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