Growth hormone

Growth hormone (GH or HGH), also known as somatotropin or somatropin, is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans.

Growth hormone is a single-chain polypeptide that is synthesized, stored, and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

Regulation of growth hormone secretion

Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus. These cells release the peptides Growth hormone-releasing hormone (GHRH or somatocrinin) and Growth hormone-inhibiting hormone (GHIH or somatostatin) into the hypophyseal portal venous blood surrounding the pituitary.

GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion.

Regulation

Stimulators of growth hormone (GH) secretion include peptide hormones, ghrelin, sex hormones, hypoglycemia, deep sleep, niacin, fasting, and vigorous exercise.

Inhibitors of GH secretion include somatostatin, circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus), hyperglycemia, glucocorticoids, and dihydrotestosterone.

Clinical significance

The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH excess. The adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.

Biotin

 Biotin helps release energy from carbohydrates and aids in the metabolism of fats, proteins and carbohydrates from food.

RDA The Adequate Intake (AI) for Biotin is 30 mcg/day for adult males and females

Biotin Deficiency Biotin deficiency is uncommon under normal circumstances, but symptoms include fatigue, loss of appetite, nausea, vomiting, depression, muscle pains, heart abnormalities and anemia.

Anaerobic organisms lack a respiratory chain. They must reoxidize NADH produced in Glycolysis through some other reaction, because NAD⁺ is needed for the Glyceraldehyde-3-phosphate Dehydrogenase reaction (see above). Usually NADH is reoxidized as pyruvate is converted to a more reduced compound, that may be excreted.

The complete pathway, including Glycolysis and the re-oxidation of NADH, is called fermentation.

For example, Lactate Dehydrogenase catalyzes reduction of the keto group in pyruvate to a hydroxyl, yielding lactate, as NADH is oxidized to NAD⁺.

Skeletal muscles ferment glucose to lactate during exercise, when aerobic metabolism cannot keep up with energy needs. Lactate released to the blood may be taken up by other tissues, or by muscle after exercise, and converted via the reversible Lactate Dehydrogenase back to pyruvate

Fermentation Pathway, from glucose to lactate (omitting H⁺):

   glucose + 2 ADP + 2 P_i → 2 lactate + 2 ATP

Anaerobic catabolism of glucose yields only 2 “high energy” bonds of ATP.

Step 1.  Acyl-CoA Dehydrogenase catalyzes oxidation of the fatty acid moiety of acyl-CoA, to produce a double bond between carbon atoms 2 and 3.

There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C), long and very long (12-18 C) chain fatty acids. Very Long Chain Acyl-CoA Dehydrogenase is bound to the inner mitochondrial membrane. The others are soluble enzymes located in the mitochondrial matrix.

FAD is the prosthetic group that functions as electron acceptor for Acyl-CoA Dehydrogenase. 

A glutamate side-chain carboxyl extracts a proton from the a-carbon of the substrate, facilitating transfer of 2 e^- with H⁺ (a hydride) from the b position to FAD. The reduced FAD accepts a second H⁺, yielding FADH₂

The carbonyl oxygen of the thioester substrate is hydrogen bonded to the 2'-OH of the ribityl moiety of FAD, giving this part of FAD a role in positioning the substrate and increasing acidity of the substrate a-proton

The reactive glutamate and FAD are on opposite sides of the substrate at the active site. Thus the reaction is stereospecific, yielding a trans double bond in enoyl-CoA.

FADH₂ of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 electrons to an Electron Transfer Flavoprotein (ETF), which in turn passes the electrons to coenzyme Q of the respiratory chain.

Step 2. Enoyl-CoA Hydratase catalyzes stereospecific hydration of the trans double bond produced in the 1st step of the pathway, yielding L-hydroxyacyl-Coenzyme A

Step 3. Hydroxyacyl-CoA Dehydrogenase catalyzes oxidation of the  hydroxyl in the b position (C3) to a ketone. NAD⁺ is the electron acceptor.

Step 4. b-Ketothiolase (b-Ketoacyl-CoA Thiolase) catalyzes thiolytic cleavage.

A cysteine S attacks the b-keto C. Acetyl-CoA is released, leaving the fatty acyl moiety in thioester linkage to the cysteine thiol. The thiol of HSCoA displaces the cysteine thiol, yielding fatty acyl-CoA (2 C shorter).

A membrane-bound trifunctional protein complex with two subunit types expresses the enzyme activities for steps 2-4 of the b-oxidation pathway for long chain fatty acids. Equivalent enzymes for shorter chain fatty acids are soluble proteins of the mitochondrial matrix.

Summary of one round of the b-oxidation pathway:

fatty acyl-CoA + FAD + NAD⁺ + HS-CoA → 
            fatty acyl-CoA (2 C shorter) + FADH₂ + NADH + H⁺ + acetyl-CoA

The b-oxidation pathway is cyclic. The product, 2 carbons shorter, is the input to another round of the pathway. If, as is usually the case, the fatty acid contains an even number of C atoms, in the final reaction cycle butyryl-CoA is converted to 2 copies of acetyl-CoA

ATP production:

• FADH₂ of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 e^- via ETF to coenzyme Q of the respiratory chain. H⁺ ejection from the mitochondrial matrix that accompanies transfer of 2 e^- from CoQ to oxygen, leads via chemiosmotic coupling to production of approximately 1.5 ATP. (Approx. 4 H⁺ enter the mitochondrial matrix per ATP synthesized.)
• NADH is reoxidized by transfer of 2 e^- to the respiratory chain complex I. Transfer of 2 e^- from complex I to oxygen yields approximately 2.5 ATP.
• Acetyl-CoA can enter Krebs cycle, where the acetate is oxidized to CO₂, yielding additional NADH, FADH₂, and ATP. 
• Fatty acid oxidation is a major source of cellular ATP

b-Oxidation of very long chain fatty acids also occurs within peroxisomes

FAD is electron acceptor for peroxisomal Acyl-CoA Oxidase, which catalyzes the first oxidative step of the pathway. The resulting FADH₂ is reoxidized in the peroxisome producing hydrogen peroxide FADH₂ + O₂ à FAD + H₂O₂

The peroxisomal enzyme Catalase degrades H₂O₂ by the reaction:
2 H₂O₂ → 2 H₂O + O₂
These reactions produce no ATP

Once fatty acids are reduced in length within the peroxisomes they may shift to the mitochondria to be catabolized all the way to CO₂. Carnitine is also involved in transfer of fatty acids into and out of peroxisomes

CHOLESTEROL AND ITS IMPORTANCE

Cholesterol is an important lipid found in the cell membrane. It is a sterol, which means that cholesterol is a combination of a steroid and an alcohol .

It is an important component of cell membranes and is also the basis for the synthesis of other steroids, including the sex hormones estradiol and testosterone, as well as other steroids such as cortisone and vitamin D.

In the cell membrane, the steroid ring structure of cholesterol provides a rigid hydrophobic structure that helps boost the rigidity of the cell membrane.

Without cholesterol the cell membrane would be too fluid. In the human body, cholesterol is synthesized in the liver.

Cholesterol is insoluble in the blood, so when it is released into the blood stream it forms complexes with lipoproteins.

Cholesterol can bind to two types of lipoprotein, called high-density lipoprotein (HDL) and low-density lipoprotein (LDL).

A lipoprotein is a spherical molecule with water soluble proteins on the exterior. Therefore, when cholesterol is bound to a lipoprotein, it becomes blood soluble and can be transported throughout the body.

HDL cholesterol is transported back to the liver. If HDL levels are low, then the blood level of cholesterol will increase.

High levels of blood cholesterol are associated with plaque formation in the arteries, which can lead to heart disease and stroke.

VITAMIN C: ASCORBIC ACID, ASCORBATE

Vitamin C benefits the body by holding cells together through collagen synthesis; collagen is a connective tissue that holds muscles, bones, and other tissues together. Vitamin C also aids in wound healing, bone and tooth formation, strengthening blood vessel walls, improving immune system function, increasing absorption and utilization of iron, and acting as an antioxidant.

RDA The Recommended Dietary Allowance (RDA) for Vitamin C is 90 mg/day for adult males and 75 mg/day for adult females

Vitamin C Deficiency

Severe vitamin C deficiency result in the disease known as scurvy, causing a loss of collagen strength throughout the body. Loss of collagen results in loose teeth, bleeding and swollen gums, and improper wound healing.