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.

Regulation of PTH secretion

Secretion of parathyroid hormone is controlled chiefly by serum [Ca²⁺] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca²⁺] is low.

Hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.

Hypermagnesemia also results in inhibition of PTH secretion.

Stimulators of PTH includes decreased serum [Ca²⁺], mild decreases in serum [Mg²⁺], and an increase in serum phosphate.

Inhibitors include increased serum [Ca²⁺], severe decreases in serum [Mg²⁺], which also produces symptoms of hypoparathyroidism (such as hypocalcemia), and calcitriol.

Erythrocytes and the Pentose Phosphate Pathway

The predominant pathways of carbohydrate metabolism in the red blood cell (RBC) are glycolysis, the PPP and 2,3-bisphosphoglycerate (2,3-BPG) metabolism (refer to discussion of hemoglobin for review of the synthesis and role role of 2,3-BPG).

Glycolysis provides ATP for membrane ion pumps and NADH for re-oxidation of methemoglobin. The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione.

The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H₂O₂, that in turn results in a weakening of the cell wall and concomitant hemolysis.

Accumulation of H₂O₂ also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall.

Glutathione removes peroxides via the action of glutathione peroxidase.

The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH.

Any defect in the production of NADPH could, therefore, have profound effects on erythrocyte survival.

COPPER

The normal serum level of copper is 25 to 50 mg/dl.

Functions of copper

(a) Copper is necessary for iron absorption and incorporation of iron into hemoglobin.

(b) It is very essential for tyrosinase activity

(c) It is the co-factor for vitamin C requiring hydroxylation

(d) Copper increases the level of high density lipo protein and protects the heart.

Wilson’s disease

In case of Wilson’s disease ceruloplasmin level in blood is drastically reduced.

Wilson’s disease leads to

(i) Accumulation of copper in liver leads to hepatocellular degeneration and cirrhosis

(ii) Deposition of copper in brain basal ganglia leads to leticular degeneration

(iii) Copper deposits as green pigmented ring around cornea and the condition is called as Kayser-Kleischer ring

Over accumulation of copper can be treated by consumption of diet containg low copper and injection of D-penicillamine, which excretes copper through urine.

Menke’s kidney hair syndrome

 It is X-linked defect. In this condition copper is absorbed by GI tract, but cannot be transported to blood. The defect in transport of copper to blood is due to absence of an intracellular copper binding ATPase.

CLINICAL SIGNIFICANCE OF ENZYMES

The measurement of enzymes level in serum is applied in diagnostic application

Pancreatic Enzymes

Acute pancreatitis is an inflammatory process where auto digestion of gland was noticed with activation of the certain pancreatic enzymes. Enzymes which involves in pancreatic destruction includes α-amylase, lipase etc.,

1.  α-amylase (AMYs) are calcium dependent hydrolyase class  of metaloenzyme that catalyzes the hydrolysis of 1, 4- α-glycosidic linkages in polysaccharides. The normal values of amylase is in range of 28-100 U/L. Marked increase of 5 to 10 times the upper reference limit (URL) in AMYs activity indicates acute pancreatitis and severe glomerular impairment.

2.  Lipase is single chain glycoprotein. Bile salts and a cofactor called colipase are required for full catalytic activity of lipase. Colipase is secreted by pancreas. Increase in plasma lipase activity indicates acute pancreatitis and carcinoma of the pancreas.

Liver Enzymes

Markers of Hepatocellular Damage

1.  Aspartate transaminase (AST) Aspartate transaminase is present in high concentrations in cells of cardiac and skeletal muscle, liver, kidney and erythrocytes. Damage to any of these tissues may increase plasma AST levels.

The normal value of AST for male is <35 U/ L and for female it is <31 U/L.

2.  Alanine transaminase (ALT) Alanine transaminase is present at high concentrations in liver and to a lesser extent, in skeletal muscle, kidney and heart. Thus in case of liver damage increase in both AST and ALT were noticed. While in myocardial infarction AST is increased with little or no increase in ALT.

The normal value of ALT is <45 U/L and <34 U/L for male and female respectively

Markers of cholestasis

1.  Alkaline phosphatases

Alkaline phosphatases are a group of enzymes that hydrolyse organic phosphates at high pH. They are present in osteoblasts of bone, the cells of the hepatobiliary tract, intestinal wall, renal tubules and placenta.

Gamma-glutamyl-transferase (GGT) Gamma-glutamyl-transferase catalyzes the transfere of the γ–glutamyl group from peptides. The activity of GGT is higher in men than in women. In male the normal value of GGT activity is <55 U/L and for female it is <38 U/L.

2.  Glutamate dehydrogenase (GLD) Glutamate dehydrogenase is a mitochondrial enzyme found in liver, heart muscle and kidneys.

Muscle Enzymes

1.  Creatine Kinase Creatine kinase (CK) is most abundant in cells of brain, cardiac and skeletal.

2.  Lactate Dehydrogenase

Lactate dehydrogenase (LD) catalyses the reversible interconversion of lactate and pyruvate.

FAT-SOLUBLE VITAMINS

The fat-soluble vitamins, A, D, E, and K, are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess than water-soluble vitamins.

VITAMIN A: RETINOL

 Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division, gene expression, and regulation of the immune system.

The skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers.

One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene. The Recommended Dietary Allowance (RDA) for vitamin A is 900 mcg/ day for adult males and 700 mcg/ day for adult females.

Vitamin A Deficiency

Vitamin A deficiency is rare, but the disease that results is known as xerophthalmia.

Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth.

Vitamin A toxicity The Tolerable Upper Intake Level (UL) for adults is 3,000 mcg RAE.

VITAMIN D

Vitamin D plays a critical role in the body’s use of calcium and phosphorous. It works by increasing the amount of calcium absorbed from the small intestine, helping to form and maintain bones.

Vitamin D benefits the body by playing a role in immunity and controlling cell growth. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth.

RDA  From 12 months to age fifty, the RDA is set at 15 mcg.

20 mcg of cholecalciferol equals 800 International Units (IU), which is the recommendation for maintenance of healthy bone for adults over fifty.

Vitamin D Deficiency

Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults may result in osteomalacia (muscle and bone weakness), and osteoporosis (loss of bone mass).

Vitamin D toxicity

The Tolerable Upper Intake Level (UL) for vitamin D is set at 100 mcg for people 9 years of age and older. High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning.

VITAMIN E: TOCOPHEROL

Vitamin E benefits the body by acting as an antioxidant, and protecting vitamins A and C, red blood cells, and essential fatty acids from destruction.

RDA  One milligram of alpha-tocopherol equals to 1.5 International Units (IU). RDA guidelines state that males and females over the age of 14 should receive 15 mcg of alpha-tocopherol per day.

Vitamin E Deficiency Vitamin E deficiency is rare. Cases of vitamin E deficiency usually only occur in premature infants and in those unable to absorb fats.

VITAMIN K

Vitamin K is naturally produced by the bacteria in the intestines, and plays an essential role in normal blood clotting, promoting bone health, and helping to produce proteins for blood, bones, and kidneys.

RDA

Males and females age 14 - 18: 75 mcg/day; Males and females age 19 and older: 90 mcg/day

Vitamin K Deficiency

Hemorrhage can occur due to sufficient amounts of vitamin K.

Vitamin K deficiency may appear in infants or in people who take anticoagulants, such as Coumadin (warfarin), or antibiotic drugs.

Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week.