practice

Explanation

Explanation

The end product of the purine nucleotides catabolism in humans and other primates is uric acid (urate) which is excreted in urine and can also cause kidney stones (renal calculi). Allopurinol and febuxostat inhibits Xanthine oxidase (XO). Hypoxanthine and Xanthine which is more soluble is excreted in urine. Purine nucleotides (adenine and guanine).  AMP – Adenosine monophosphate; GMP – Guanosine monophosphate

Pyrimidine (thymine, Uracil, cytosine); catabolism of thymine and uracil gives urea, while catabolism of cytosine gives β-alanine.

Explanation

Explanation

Vitamin B6 is a cofactor in decarboxylation reactions.   

Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

         Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

Lactate, formed by the action of lactate dehydrogenase (converting pyruvate to lactate) is the final product of anaerobic glycolysis in eukaryotic cells. In organs or cells that are poorly vascularized and/or lack mitochondria, formation of lactate is the major fate of pyruvate as seen in lens, cornea of the eye, kidney medulla, testes, leukocytes and red blood cells.

Aerobic glycolysis progresses to citric acid cycle from pyruvate. The cycle occurs totally in the mitochondria.

Explanation

Vitamin B₆ (pyridoxine): converted to pyridoxal phosphate (PLP), a cofactor used in transamination (e.g. in ALT and AST), decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathione, heme, niacin (Vit. B₃), histamine and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine and GABA. Deficiency produces convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by isoniazid and oral contraceptives), sideroblastic anemia due to impaired hemoglobin synthesis and iron excess.

Explanation

Prokaryotic operons contain an operator – a segment of DNA that regulates the activity of the structural genes of the operon. If the operator is not bound by a repressor molecule, RNA polymerase passes over the operator and reaches the protein-coding genes which it transcribes to mRNA. If a repressor molecule is bound to the operator, the polymerase is blocked and does not produce mRNA. As long as the repressor is bound to the operator, no transcription and therefore no proteins are made. However, when an inducer molecule is present, it binds to the repressor, causing the repressor to change shape so that it no longer binds the operator. When this happens, the RNA polymerase can proceed with transcription.

Explanation

The findings are specific for obstruction of bile duct and bile acid deficiency.

Findings:

* malabsorption: bile salts do not enter the Small Intestine; no emulsification of fat.

*light coloured stool: due to lack of urobilin (which leads to lack of stercobilin).

*Jaundice (posthepatic, mechanic, obstructive): increased conjugated Bilirubin.

* Steatorrhea

Explanation

When adrenocorticotropic hormone (ACTH) is secreted by the anterior pituitary gland, several other hormones that have similar chemical structures are secreted simultaneously. The reason for this is that the gene that is transcribed to form the RNA molecule that causes ACTH synthesis initially causes the formation of a considerably larger protein, a preprohormone called proopiomelanocortin (POMC), which is the precursor of ACTH (corticotrophin) and several other peptides, including melanocyte-stimulating hormone (melanotropin), β-lipotropin, β-endorphin and a few others.

Explanation

Congenital deficiency of homogentisate oxidase (homogentisic acid oxidase) in the degradative pathway of tyrosine to Fumarate → pigment-forming homogentisic acid accumulates (homogentisuria) in tissues. Autosomal recessive. Usually benign. Urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Explanation

Phenylketones – phenylacetate, phenyllactate and phenylpyruvate. These compounds are not normally produced in significant amounts in the presence of functional phenylalanine hydroxylase, but are elevated in phenylketonuria. These metabolites give urine a characteristic musty (“mousey”) odour. The disease acquired its name from the presence of a phenylketone (now known to be phenylpyruvate) in the urine.

Phenylketonuria (PKU) is caused by a deficiency of phenylalanine hydroxylase. PKU is the most common clinically encountered inborn error of amino-acid metabolism. Biochemically, it is characterized by accumulation of phenylalanine and a deficiency of tyrosine. It may also be caused by deficiencies in tetrahydrobiopterin cofactor (BH₄) or in dihydropteridine (BH₂) reductase, which regenerates BH₄ from BH₂.

Explanation

Erythropoietic porphyria (Gunther’s disease): This disorder is due to a defect in the enzyme Uroporphyrinogen III cosynthase. It is characterized by:

* It is a rare congenital disorder caused by autosomal recessive mode of inheritance, mostly confined to erythropoietic tissues.

* The individuals excrete Uroporphyrinogen I and Coproporphyrinogen I which oxidize respectively to Uroporphyrin I and Coproporphyrin I (red pigments).

* The patients are photosensitive (itching and burning of skin when exposed to visible light) due to the abnormal porphyrins that accumulate. Porphyrins are accumulated in the teeth, bones and an increases amount are seen in the plasma, bone marrow, faeces, RBCs and urine.

* Increased hemolysis is also observed in the individuals affected by this disorder.

Explanation

Athletes that are exercising intensely for the short periods of time, such as in a sprint race, build up large amounts of lactate in their muscles as the result of anaerobic glycolysis. The “warming down” period of continual movement under aerobic conditions performed by athletes for approximately 15mins after a race increases circulation and removes lactate from the muscles. Aerobic glycolysis progresses to citric acid cycle from pyruvate. The cycle occurs totally in the mitochondria.

Lactate, formed by the action of lactate dehydrogenase (converting pyruvate to lactate) is the final product of anaerobic glycolysis in eukaryotic cells. In organs or cells that are poorly vascularized and/or lack mitochondria, formation of lactate is the major fate of pyruvate as seen in lens, cornea of the eye, kidney medulla, testes, leukocytes and red blood cells.

Explanation

Maple syrup urine disease results from blocked degradation of branched amino acids (isoleucine, leucine, valine) due to decreased activity or deficiency of α-ketoacid dehydrogenase. It causes increase α-ketoacids in the blood, especially those of leucine. It also causes severe CNS defects, intellectual disability and death. It is an autosomal recessive disease. Urine smells like maple syrup/burnt sugar. Treatment: restriction of isoleucine, leucine, valine in diet and thiamine supplementation.

Explanation

The major pathway for catabolism of saturated fatty acids is a mitochondrial pathway called β-oxidation. After a long-chain fatty acid (LCFA) enters a cell, it is converted in the cytosol to its Co-A derivative. Because β-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across inner mitochondrial membrane which is impermeable to Co-A. therefore, a specialized carrier transports the long chain acyl group from the cytosol into the mitochondrial matrix. This carrier is carnitine and this rate-limiting transport process is called the carnitine shuttle. Since carnitine helps the mitochondria utilize energy, it plays a critical role in reducing the occurrence and impact of obesity. In addition to helping the mitochondria burn fat as energy, carnitine is also vital for removing waste products from mitochondria. Obesity and aging contribute to low carnitine levels, which compromises mitochondrial performance and increases insulin resistance, promoting further obesity and carnitine reduction.

Explanation

     Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

          Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

Calcium (above 98%) and phosphorus (about 86%) are mainly fixed in bones and teeth, from where they can be mobilized in case of immediate organism needs. The role of calcium in the organism consists in the participation in bone and teeth construction, transmission of nervous stimulation, blood clotting, regulation of membranes permeability, muscle contraction etc. Therefore, a deficiency of Ca²⁺ → ↓density of teeth and ↑fragility.

Explanation

Substances absorbed into the bloodstream from the intestine pass through the liver, where toxins are normally removed. Many of these toxins (such as ammonia) are normal breakdown products of the digestion of protein.  Ammonia is produced by amino acid metabolism and intestinal urease-positive bacteria. In physiological conditions, it is mostly present as ammonium (NH₄⁺) in serum. The urea or ornithine cycle, which is fully expressed in the liver exclusively, serves to converts NH₄⁺ to urea prior to renal excretion and to maintain low serum concentrations. 

NH₃ + α-ketoglutarate → Glutamate

α-ketoglutarate is used up which leads to:

·        ↑glutamate → ↑GABA (inhibitory neurotransmitter)

·        Inhibition of citric acid cycle/tricarboxylic acid cycle; this causes impairment of ATP formation.

·        Inhibition of metabolism of amino acids (impairment of transamination reactions).

NH₃ + Glutamate → Glutamine

Glutamine is an amide of glutamic acid which provides a non-toxic storage and transport form of ammonia (NH₃). Ammonia increase synthesis of glutamine in brain. Accumulation of glutamine in brain results in elevation of osmotic pressure in nervous cells leading to brain edema.

                                    NH₃ + H⁺ → NH₄⁺

In blood ammonia (NH₃) is represented as ammonium ion (NH₄⁺). Accumulation of ammonium ion impairs transport of ions (Na⁺, K⁺) through cell membranes and failure of transmission of nerve impulse.

            Glutamine toxicity in brain is dependent on increased ammonia concentration. 

Explanation

Hippuric acid has been a major human metabolite for years. However, there is no well-known documented health benefit associated with it except for excretion of environmental-toxic exposures of aromatic compounds such as toluene or from dietary protein degradation and resynthesis by intestinal microflora metabolism of quinic acid via the shikimate pathway. Thus hippuric acid can appear in humans as an excretory product from natural or unnatural sources. It has been believed over the years that the major source of urinary hippuric acid levels in humans has come from environmental toxic solvent exposures.

Explanation

Vitamin K is essential for the formation of various clotting factors in the liver, namely clotting factor II, VII, IX and X; Protein C and S.

Factor II – Prothrombin

Factor VII – Stable factor

Factor IX – Christmas factor

Factor X – Stuart-Prower factor

These factors undergo vitamin K-dependent post-translational modification, whereby a number of their glutamic acid residues are carboxylated to form ɣ-carboxyglutamic acid residues. The ɣ-carboxyglutamyl residues bind calcium ions which are essential for interaction between the coagulation factors and platelet membranes. This oral anticoagulants block epoxide reductase and creation of active form of vitamin K resulting in disturbances in prothrombin and proconvertin synthesis in liver.

Deficiency of vitamin K → ↓clotting factors → prolongation of coagulation time → hemorrhages.

Explanation

Explanation

Parathyroid hormone: secreted by chief cells of parathyroid gland. Effects include:

↑bone resorption of Ca²⁺ and PO₄^3- → ↑their plasma levels

↑kidney reabsorption of Ca²⁺ in distal convoluted tubule → ↑ Ca²⁺ plasma level

↓reabsorption of PO₄^3- in proximal convoluted tubule → ↓ PO₄^3- plasma levels

↑Calcitriol (vit D₃) production by stimulating kidney 1α-hydroxylase in proximal convoluted tubule. It increases Ca²⁺ and PO₄^3- absorption in the intestine.

In general, parathyroid hormone ↑ Ca²⁺ plasma level but ↓ PO₄^3- plasma levels. Abnormal synthesis (↑synthesis) of parathyroid hormone can lead to hypercalcemia and hypophosphatemia.

Explanation

Vitamin B6 (pyridoxine): coenzyme forms – Pyridoxal phosphate (PALP)

                                                                         Pyridoxamine Phosphate (PAMP)

Components of pyridoxal enzymes used in transamination (e.g. ALT and AST); decarboxylation reactions, glycogen phosphorylase, transformation of tryptophan to Niacin (Vit B3), active transport of amino acids through the cell membrane, synthesis of cystathionine, heme, histamine and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine and GABA.

Explanation

Cholelithiasis is obstruction of bile duct by a stone.

Obturation (obstruction, to close) of bile duct – it can be:

* Intrahepatic – blockage of intrahepatic bile ducts

* Extrahepatic – blockage of common bile duct (ductus choledochus).

Findings:

* malabsorption: bile salts do not enter the Small Intestine; no emulsification of fat.

*light coloured stool: due to lack of urobilin (which leads to lack of stercobilin).

*Jaundice (posthepatic, mechanic, obstructive): increased conjugated Bilirubin.

* Steatorrhea

The findings are specific for obstruction of bile duct and bile acid deficiency.

Explanation

The end product of the purine nucleotides catabolism in humans and other primates is uric acid (urate) which is excreted in urine. Allopurinol and febuxostat inhibits Xanthine oxidase (XO). Hypoxanthine and Xanthine which is more soluble is excreted in urine. Purine nucleotides (adenine and guanine).  AMP – Adenosine monophosphate; GMP – Guanosine monophosphate

Pyrimidine (thymine, Uracil, cytosine); catabolism of thymine and uracil gives urea, while catabolism of cytosine gives β-alanine.

Explanation

Vitamin C (ascorbic acid): found in fruits and vegetables; an antioxidant; also facilitates iron absorption by reducing it to Fe²⁺ state. It is necessary for hydroxylation of proline and lysine in collagen synthesis; necessary for dopamine β-hydroxylase, which converts dopamine to norepinephrine. Deficiency leads to: scurvy – swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair; Weakened immune response.

Type III collagen is found in blood vessels; Type IV collagen is found in basement membrane. Deficiency in Vitamin C disrupts the second stage of collagen synthesis in fibroblasts (hydroxylation of collagen) which results in petechiae, bruising, hemarthrosis.

Explanation

Lactate, formed by the action of lactate dehydrogenase (converting pyruvate to lactate) is the final product of anaerobic glycolysis in eukaryotic cells. In organs or cells that are poorly vascularized and/or lack mitochondria, formation of lactate is the major fate of pyruvate as seen in lens, cornea of the eye, kidney medulla, testes, leukocytes and red blood cells.

Athletes that are exercising intensely for the short periods of time, such as in a sprint race, build up large amounts of lactate in their muscles as the result of anaerobic glycolysis. The “warming down” period of continual movement under aerobic conditions performed by athletes for approximately 15mins after a race increases circulation and removes lactate from the muscles.

Explanation

Collagen, most abundant protein in human body; organizes and strengthens extracellular matrix. Collagen contains Gly-X-Y (X and Y are proline or lysine). Glycine(Gly) makes 1/3 of collagen. Oxyproline (hydroxyproline) is a major collagen amino acid which enables it to be regarded as a marker that reflects the catabolism of collagen.

Explanation

A large number of components are required for translation (synthesis of a protein). These include all the amino acids that are found in the finished product, the mRNA to be translated, tRNA, functional ribosomes, energy sources and enzymes as well as protein factors needed for initiation, elongation and termination of the polypeptide chain. In eukaryotic cells, the ribosomes are either “free” in the cytosol or are in close association with the endoplasmic reticulum (which is then known as the “rough” endoplasmic reticulum or RER). The RER – associated ribosomes are responsible for synthesizing proteins that are to be exported from the cell as well as those that are destined to become integrated into plasma, endoplasmic reticulum or golgi membranes or incorporated into lysosomes.

Explanation

In the hepatocyte, the solubility of unconjugated bilirubin is increased (i.e. it is made soluble) by the addition of two molecules of glucuronic acid to produce conjugated bilirubin. This process is reffered to as conjugation. This reaction is catalyzed by Uridine diphosphate (UDP) glucuronyltransferase – UGT. Varying degrees of deficiency of this enzyme result in Crigler-Najjar I & II and Gilbert syndrome; with Crigler-Najjar I being the most severe deficiency.

Deficiency of UGT inhibits conjugation and therefore increase unconjugated bilirubin in serum (Jaundice).

Explanation

A large number of components are required for translation (synthesis of a protein). These include all the amino acids that are found in the finished product, the mRNA to be translated, tRNA, functional ribosomes, energy sources and enzymes as well as protein factors needed for initiation, elongation and termination of the polypeptide chain. In eukaryotic cells, the ribosomes are either “free” in the cytosol or are in close association with the endoplasmic reticulum (which is then known as the “rough” endoplasmic reticulum or RER). The RER – associated ribosomes are responsible for synthesizing proteins that are to be exported from the cell as well as those that are destined to become integrated into plasma, endoplasmic reticulum or golgi membranes or incorporated into lysosomes.

Explanation

The end product of the purine nucleotides catabolism in humans and other primates is uric acid (urate) which is excreted in urine. Allopurinol and febuxostat inhibits Xanthine oxidase (XO). Hypoxanthine and Xanthine which is more soluble is excreted in urine. Purine nucleotides (adenine and guanine).  AMP – Adenosine monophosphate; GMP – Guanosine monophosphate

The last two steps in uric acid biosynthesis is catalyzed by xanthine oxidase.  Deficiency of this enzyme can lead to reduction in the uric acid concentration.

Explanation

Serotonin, also called 5-hydroxytryptamine, is synthesized and stored at several sites in the body. It can be found in the intestinal mucosa, central nervous system and in platelets. Serotonin is synthesized from tryptophan, which is hydroxylated. The product, 5-hydroxytryptophan is decarboxylated to serotonin, which is also degraded by monoamine oxidase (MAO). Serotonin has multiple physiologic roles, including pain perception, affective disorders, and regulation of sleep, temperature and blood pressure.

3-hydroxyanthranilic acid is an intermediate in the metabolism of tryptophan.

Explanation

     The P450 system is impotant for the metabolism of many endogenous compounds (such as steroids, lipids etc) and for the biotransformation of exogenous substances (xenobiotics). Cytochrome P450, designated as CYP, is a superfamily of heme-containing isozymes that are located in most cells but are primarily found in the liver and GIT. Phase I reactions utilizing the P450 system (also called microsomal mixed function oxidases). The oxidation proceeds by the xenobiotic binding to the oxidized form of cytochrome P450 and then O₂ is introduced through a reductive step, coupled to NADPH: cytochrome P450 oxidoreductase.

Explanation

The Mucopolysaccharidoses are hereditary disorders that are clinically progressive. They are characterized by accumulation of glycosaminoglycans in various tissues, causing varied symptoms such as skeletal and extracellular matrix deformities and mental retardation. Mucopolysaccharidoses are caused by a deficiency of any one of the lysosomal hydrolases normally involved in the degradation of heparin sulfate and/or dermatan sulfate. This results in the presence of oligosaccharides in the urine because of incomplete lysosomal degradation of glycosaminoglycans.

Explanation

In urea or ornithine cycle, the first two reactions leading to the synthesis of urea occur in the mitochondria, whereas the remaining cycle enzymes are located in the cytosol. The first reaction is formation of carbomoyl phosphate and the second reaction is formation of citrulline. Ornithine and citrulline are basic amino acids that participate in the urea cycle. The release of the high energy phosphate of carbomoyl phosphate as inorganic phosphate drives the reaction in the forward direction. The reaction product – Citrulline is transported to the cytosol where it condenses with aspartate to form argininosucinate. Increased concentration of citrulline in urine and blood indicates a defect in ornithine or urea cycle.

Explanation

Genes are contained in a complex of DNA and proteins (mostly histones) called chromatin and its basic unit of structure is the nucleosome. Each nucleosome is composed of an octamer (8) of histone proteins and approximately 140 base pairs of DNA. Nucleosomes themselves are joined into clusters by binding of DNA existing between nucleosomes (linker DNA) with other histone proteins. Nucleosomes keep the DNA tightly coiled such that it cannot be transcribed.

Explanation

    Lactase (β-galactosidase) cleaves lactose (in milk) producing galactose and glucose. Hereditary deficiencies of lactase have been reported in infants and children with dissacharide intolerance. Treatment for this disorder is to reduce consumption of milk. This is seen when the milk is substituted by glucose solution.

Explanation

Lactate, formed by the action of lactate dehydrogenase (converting pyruvate to lactate) is the final product of anaerobic glycolysis in eukaryotic cells. In organs or cells that are poorly vascularized and/or lack mitochondria, formation of lactate is the major fate of pyruvate as seen in lens, cornea of the eye, kidney medulla, testes, leukocytes and red blood cells.

Aerobic glycolysis progresses to citric acid cycle from pyruvate. The cycle occurs totally in the mitochondria.

       Athletes that are exercising intensely for the short periods of time, such as in a sprint race, build up large amounts of lactate in their muscles as the result of anaerobic glycolysis. The “warming down” period of continual movement under aerobic conditions performed by athletes for approximately 15mins after a race increases circulation and removes lactate from the muscles.

Explanation

     Gluconeogenesis is making of glucose from non-carbohydrate sources i.e. fat and proteins. During a prolonged fast, hepatic glycogen stores are depleted and glucose is formed from precursors such as lactate, pyruvate, glycerol (derived from backbone of triacylglycerols) and α-ketoacids (derived from the catabolism of glucogenic amino acids). Amino acids derived from hydrolysis of tissue proteins (e.g. muscle proteins) are the major sources of glucose during a fast. α-ketoacids such as oxaloacetate and α-ketoglutarate are derived from the metabolism of glucogenic amino acids. Amino acids whose catabolism yields pyruvate or one of the intermediates of citric acid cycle (CAC) are termed glucogenic or glycogenic e.g. alanine, arginine, aspartate, histidine etc.

Explanation

The major pathway for catabolism of saturated fatty acids is a mitochondrial pathway called β-oxidation. After a long-chain fatty acid (LCFA) enters a cell, it is converted in the cytosol to its Co-A derivative. Because β-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across inner mitochondrial membrane which is impermeable to Co-A. therefore, a specialized carrier transports the long chain acyl group from the cytosol into the mitochondrial matrix. This carrier is carnitine and this rate-limiting transport process is called the carnitine shuttle. Since carnitine helps the mitochondria utilize energy, it plays a critical role in reducing the occurrence and impact of obesity. In addition to helping the mitochondria burn fat as energy, carnitine is also vital for removing waste products from mitochondria. Obesity and aging contribute to low carnitine levels, which compromises mitochondrial performance and increases insulin resistance, promoting further obesity and carnitine reduction.

Explanation

     The process of transcription of a typical gene can be divided into 3 phases: initiation, elongation and termination. The process of transcription begins with the binding of the RNA polymerase holoenzyme to a regionof the DNA known as the promoter. RNA polymerase is a multisubunit enzyme that recognizes a nucleotide sequence (the promoter region) at the beginning of a length of DNA that is to be transcribed. It makes a complementary RNA copy of the DNA template strand and then recognizes the end of the DNA sequence to be transcribed (the termination region).

Explanation

Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

         Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

     Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

         Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

     Thiamine (vitamin B₁): thiamine pyrophosphate (TPP) is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from ATP to thiamine. Biological role of TPP: it is a component of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes catalyzing the reactions of oxidative decarboxylation of pyruvate and α-ketoglutarate (kreb’s cycle) i.e. it promotes energy formation from carbohydrates and lipids. It’s also a component of transketolase (pentose phosphate pathway of glucose oxidation) essential for fats and nucleic acids synthesis.

Explanation

Crigler Najjar syndrome type II is a rare hereditary disorder and is due to a less severe defect in the bilirubin conjugation. It is believed that hepatic UDP-glucuronyltransferase that catalyzes the addition of second glucuronyl group is defective. It is treated with Phenobarbital ( a barbiturate), because it induces the action of UDP-glucuronyltransferase, thereby producing more conjugated (direct) bilirubin.

Explanation

     Human immunodeficiency virus (HIV): diploid genome (2 molecules of RNA). The 3 structural genes(i.e. proteins coded for by the genes) are:

·        env (gp 120 and gp 41): formed from cleavage of gp 160 to form envelope glycoproteins. gp 120 is for attachment to host CD4+ T cell. gp 41 is for fusion and entry.

·        Gag (p24): capsid protein

·        pol: reverse transcriptase, aspartate protease, integrase.

ELISA/Western blot (immunoblot) tests look for antibodies to the viral proteins listed above.

Reverse transcriptase synthesizes dsDNA (ds-double stranded) from genomic RNA (mRNA); dsDNA integrates into host genome. Virus binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection) or CXCR4 on I cells (late infection).

·        Homozygous CCR5 mutation – immunity

·        Heterozygous CCR5 mutation – slower course.

Explanation

     Thiamine (vitamin B₁): thiamine pyrophosphate (TPP) is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from ATP to thiamine. Biological role of TPP: it is a component of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes catalyzing the reactions of oxidative decarboxylation of pyruvate and α-ketoglutarate (kreb’s cycle) i.e. it promotes energy formation from carbohydrates and lipids. It’s also a component of transketolase (pentose phosphate pathway of glucose oxidation) essential for fats and nucleic acids synthesis.

Pyruvate to acetyl CoA + CO₂ reaction

            If pyruvate dehydrogenase cannot function properly due to vitamin B₁ deficiency, then pyruvate will be accumulated in blood because it can’t be broken down.

Explanation

     Cystinuria is a disorder of the proximal tubules reabsorption of filtered cystine and dibasic amino acids (lysine, ornithine, arginine). The inability to reabsorb cystine leads to accumulation and subsequent precipitation of stones of cystine in the urinary tract. It is an inherited disorder of amino acid transport. The disease expresses itself clinically by the precipitation of cystine to form kidney stones (calculi), which can block the urinary tract. Oral hydration is an important part of treatment for this disorder. Cystine is formed from two molecules of cysteine joined together.

Explanation

Urea is the major disposal form of amino groups derived from amino acids and account for about 90% of the nitrogen-containing components of urine. Formation of carbomoyl phosphate by carbomoyl phosphate synthetase I is driven by cleavage of two molecules of ATP. Ammonia is incorporated into carbamoyl phosphate. Ultimately, the nitrogen atom derived from this ammonia becomes one of the nitrogens of urea. NB: carbamoyl phosphate synthetase II participates in the biosynthesis of pyrimidines. However, when the function of carbomoyl phosphate synthetase I is compromised, blood ammonia levels rise and urea synthesis is disturbed.

Explanation

     Cabbage juice is one of the most healing nutrients for ulcer repair as it is a huge source of vitamin U (vitamin U is actually not a vitamin but an enzyme known as S-methylmethionine). Research shows that vitamin U, administered as raw cabbage juice, is effective in promoting the rapid healing of peptic ulcers. Potatoes on the other hand are rich sources of vitamins and minerals. Several studies, such as the one published in the June 2008 edition of the “Journal of vascular nursing”, have shown reduced levels of vitamin A in patients suffering from leg ulcers, indicating a connection between the two, probably because vitamin A helps to form and maintain healthy skin, mucous membrane and teeth. Vitamin A and the amino acid glutamine help to regenerate healthy epithelial cells.

Explanation

The end product of the purine nucleotides catabolism in humans and other primates is uric acid (urate) which is excreted in urine. Allopurinol and febuxostat inhibits Xanthine oxidase (XO). Hypoxanthine and Xanthine which is more soluble is excreted in urine. Purine nucleotides (adenine and guanine).  AMP – Adenosine monophosphate; GMP – Guanosine monophosphate

Pyrimidine (thymine, Uracil, cytosine); catabolism of thymine and uracil gives urea, while catabolism of cytosine gives β-alanine.

Explanation

Vit. B₃ (Niacin, PP): coenzyme forms NAD⁺, NADP⁺ is derived from tryptophan. Synthesis requires Vit. B₂ and B₆.

Vitamin B₃ (niacin) is very high in fish and meat products.

Explanation

     Isoenzyme is any of several forms of an enzyme that all catalyze the same reaction but may differ in reaction rate, inhibition by various substances, electrophoretic mobility or immunologic properties. Examples of important enzymes with isoenzymic forms are:

·        Lactate dehydrogenase: LDH₁, LDH₂, LDH₃, LDH₄, LDH₅, (5 isoenzymic forms).

·        Creatine kinase (CK): CK-MM; CK-MB; CK-BB (3 isoenzymic forms)

Explanation

Vitamin C (ascorbic acid): found in fruits and vegetables; an antioxidant; also facilitates iron absorption by reducing it to Fe²⁺ state. It is necessary for hydroxylation of proline and lysine in collagen synthesis; necessary for dopamine β-hydroxylase, which converts dopamine to norepinephrine. Deficiency leads to: scurvy – swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair; Weakened immune response.

Type III collagen is found in blood vessels; Type IV collagen is found in basement membrane. Deficiency in Vitamin C disrupts the second stage of collagen synthesis in fibroblasts (hydroxylation of collagen) which results in petechiae, bruising, hemarthrosis.

Explanation

Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

         Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

Osteolaterism results in conditions of deficiency or non-functional lysyl oxidase. Lysyl oxidase is involved in the cross-linking of elastin and collagen resulting in disorganized connective tissue formation. Lysyl oxidase is an extracellular copper enzyme that catalyzes formation of aldehydes from lysine residues in collagen and elastin precursors. This results in cross-linking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin.

Explanation

Ochronosis (Alkaptonuria): congenital deficiency of homogentisate oxidase (homogentisic acid oxidase) in the degradative pathway of tyrosine to Fumarate → pigment-forming homogentisic acid accumulates (homogentisuria) in tissues. Autosomal recessive. Usually benign. Urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Explanation

The mobilization of stored fat requires the hydrolytic release of fatty acids and glycerol from their triacylglycerol (TAG) form. This process is initiated by hormone-sensitive lipase, which removes a fatty acid from carbon 1 and/or carbon 3 of the TAG. This enzyme is activated when phosphorylated by cyclic AMP (cAMP)-dependent protein kinase. cAMP is produced in the adipocyte when one of several hormones (such as epinephrine or glucagon – stress hormones) binds to receptors on the cell membrane and activates adenylyl cyclase.

Explanation

Collagen, most abundant protein in human body; organizes and strengthens extracellular matrix. Collagen contains Gly-X-Y (X and Y are proline or lysine). Glycine(Gly) makes 1/3 of collagen. Oxyproline (hydroxyproline) is a major collagen amino acid which enables it to be regarded as a marker that reflects the catabolism of collagen.

Explanation

Explanation

Hyperammonemia can be acquired (e.g. liver disease) or hereditary (e.g. urea cycle enzyme deficiencies). Acquired hyperammonemia may be a result of an acute process e.g. viral hepatitis, ischemia or hepatotoxins. As a result, the detoxification of ammonia (i.e. its conversion to urea) is severely impaired, leading to elevated levels of circulating ammonia.

Explanation

In the liver and muscle, insulin increases glycogen synthesis. In the muscle and adipose tissue, insulin increases glucose uptake by increasing the number of glucose transporters (GLUT-2) in the cell membrane. Insulin is an anabolic hormone; it increases glucose uptake, glycogen synthesis, protein synthesis, fat synthesis; and decrease gluconeogenesis, glycogenolysis, lipolysis. Gluconeogenesis is the production of glucose from non-carbohydrate sources.

Glucagon is a functional antagonist of insulin.

Explanation

     Phenylketones – phenylacetate, phenyllactate and phenylpyruvate. These compounds are not normally produced in significant amounts in the presence of functional phenylalanine hydroxylase, but are elevated in phenylketonuria. These metabolites give urine a characteristic musty (“mousey”) odour. The disease acquired its name from the presence of a phenylketone (now known to be phenylpyruvate) in the urine.

Phenylketonuria (PKU) is caused by a deficiency of phenylalanine hydroxylase. PKU is the most common clinically encountered inborn error of amino-acid metabolism. Biochemically, it is characterized by accumulation of phenylalanine and a deficiency of tyrosine. It may also be caused by deficiencies in tetrahydrobiopterin cofactor (BH₄) or in dihydropteridine (BH₂) reductase, which regenerates BH₄ from BH₂.

Explanation

Vitamin C (ascorbic acid): found in fruits and vegetables; an antioxidant; also facilitates iron absorption by reducing it to Fe²⁺ state. It is necessary for hydroxylation of proline and lysine in collagen synthesis; necessary for dopamine β-hydroxylase, which converts dopamine to norepinephrine. Deficiency leads to: scurvy – swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair; Weakened immune response.

Type III collagen is found in blood vessels; Type IV collagen is found in basement membrane. Deficiency in Vitamin C disrupts the second stage of collagen synthesis in fibroblasts (hydroxylation of collagen) which results in petechiae, bruising, hemarthrosis.

Vitamin P (rutin) – permeability vitamin. They reduce permeability of blood vessels, especially capillaries. It prevents hyaluronic acid (the basic compound of the extracellular matrix) from degeneration by inhibition of the enzyme hyaluronidase. Ascorutin is a drug containing vitamin C and P; it is used to decrease the permeability of blood vessels.

Explanation

Hepatic steatosis can occur when humans are deprived of choline.

Choline + Phosphatidic acid → Phosphatidylcholine (lecithin, PC). In the liver PC can also be synthesized from phosphatidylserine (PS) and phosphatidylethanolamine (PE), when free choline levels are low, because it exports significant amounts of PC in bile and as a component of serum lipoproteins (needed for fat metabolism)

PS → PE →→→ PC. 3 methylation reactions between PE and PC. S-adenosylmethionine is the methyl group donor. If choline, phosphatidylcholine or methionine is deficient, there will be abnormal phospholipid synthesis, oxidative damage caused by mitochondrial dysfunction, lipoprotein secretion (remember, if VLDL cannot be secreted it will be accumulated & cause fatty liver degeneration as seen in hepatic steatosis). PC is also a major lipid component of lung surfactant.

Vitamin B₁₂ is a cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase. Both vitamin B₁₂ and B₆ are needed in fatty acid (FA) metabolism.

Explanation

     Glycogen phosphorylase is the rate-determining enzyme in Glycogenolysis (break down of glycogen). Glycogen phosphorylase cleaves glycogen to glucose 1-phosphate (first step in glycogenolysis). This pathway mobilizes stored glycogen in liver to replenish used glucose. It also breaks down glycogen in muscle to glucose, to produce energy during physical work. If this enzyme is deficient, then used glucose cannot be replaced leading to hypoglycemia.

In lysosomal glycosidase, there is still normal blood sugar levels (no hypoglycemia). α-amylase and ɣ-amylase is involved in digestion of polysaccharides. Glucose 6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in pentose phosphate pathway which catalyzes an irreversible oxidation of glucose 6-phosphate to 6-phosphogluconolactone.

Explanation

The pathway of protein synthesis translates the 3-letter alphabet of nucleotide sequences on mRNA into the twenty-letter alphabet of amino acids that constitute proteins. mRNA convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression. As in DNA, mRNA genetic information is in the sequence of nucleotides, which are arranged into codons consisting of 3 bases each. Each codon encodes for a specific amino acid, except the stop codons, which terminate protein synthesis. The mRNA is translated from its 5’-end to its 3’-end, producing a protein synthesized from its amino-terminal end to its carboxyl-terminal end.

Explanation

Lesch-Nyhan syndrome: defective purine salvage due to absent hypoxanthine-guanine phosphoribosyl transferase (HGPRT), which converts hypoxanthine to inosine monophosphate (IMP) and guanine to Guanosine monophosphate (GMP). Results in excess uric acid production and de novo purine synthesis. This syndrome is X-linked recessive. Findings: intellectual disability, self-mutilation, aggression, hyperuricemia, gout, dystonia. It can be treated with allopurinol and febuxostat.

Explanation

In mitochondria, pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate (in gluconeogenesis). This enzyme requires biotin and ATP. Oxaloacetate can replenish citric acid cycle (CAC) or be used in gluconeogenesis. So, a deficiency of pyruvate decarboxylase impairs both CAC and gluconeogenesis.

Explanation

Exposure of a cell to ultraviolet (UV) light can result in the covalent joining of two adjacent pyrimidines (usually thymine), producing a dimer. These thymine dimers prevent DNA polymerase from replicating the DNA strand beyond the site of dimer formation. First, a UV-specific endonuclease recognizes the dimer an cleaves the damaged strand on both the 5’-side and 3’-side of the dimer. Pyrimidine dimers can be formed in the skin cells of humans exposed to unfiltered sunlight. In the rare genetic disease Xeroderma pigmentosum, the cells cannot repair the damaged DNA because UV-specific endonuclease is defective, resulting in extensive accumulation of mutations and consequently, skin cancers.

Explanation

The major pathway for catabolism of saturated fatty acids is a mitochondrial pathway called β-oxidation. After a long-chain fatty acid (LCFA) enters a cell, it is converted in the cytosol to its Co-A derivative. Because β-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across inner mitochondrial membrane which is impermeable to Co-A. therefore, a specialized carrier transports the long chain acyl group from the cytosol into the mitochondrial matrix. This carrier is carnitine and this rate-limiting transport process is called the carnitine shuttle. Since carnitine helps the mitochondria utilize energy, it plays a critical role in reducing the occurrence and impact of obesity. In addition to helping the mitochondria burn fat as energy, carnitine is also vital for removing waste products from mitochondria. Obesity and aging contribute to low carnitine levels, which compromises mitochondrial performance and increases insulin resistance, promoting further obesity and carnitine reduction.

Explanation

Electrophoresis uses the principle of electric charge size and shape to separate substances. Proteins carry a positive or a negative electrical charge and they move in fluid when placed in an electrical field. The two major types of protein present in the serum are albumin and globulin proteins. Albumin is the major protein component of serum and represents the largest peak that lies closest to the positive electrode. Globulins comprise a much smaller fraction of the total serum protein but represent the primary focus of interpretation of serum protein electrophoresis. Five (5) globulin categories are expressed – α₁, α₂, (alpha 1 & 2), β₁, β₂ (beta 1 & 2) and ɣ (gamma). ɣ is the closest to the positive electrode.

Explanation

In the hepatocyte, the solubility of unconjugated bilirubin is increased (i.e. it is made soluble) by the addition of two molecules of glucuronic acid to produce conjugated bilirubin. This process is reffered to as conjugation. This reaction is catalyzed by Uridine diphosphate (UDP) glucuronyltransferase – UGT. Varying degrees of deficiency of this enzyme result in Crigler-Najjar I & II and Gilbert syndrome; with Crigler-Najjar I being the most severe deficiency.

Deficiency of UGT inhibits conjugation and therefore increase unconjugated bilirubin in serum (Jaundice).

Explanation

Norepinephrine (noradrenaline), epinephrine (adrenaline) and dopamine are catecholamines produced in chromaffin cells of adrenal medulla from tyrosine. The catecholamines are inactivated by oxidative deamination catalyzed by monoamine oxidase (MAO) and by O-methylation carried out by Catechol-O-methyltransferase. The metabolic products of these reactions are excreted in the urine as vanillymandelic acid from epinephrine and norepinephrine; and homovanillic acid from dopamine.

Explanation

Vitamin C (ascorbic acid): found in fruits and vegetables; an antioxidant; also facilitates iron absorption by reducing it to Fe²⁺ state. It is necessary for hydroxylation of proline and lysine in collagen synthesis; necessary for dopamine β-hydroxylase, which converts dopamine to norepinephrine. Deficiency leads to: scurvy – swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair; Weakened immune response.

Type III collagen is found in blood vessels; Type IV collagen is found in basement membrane. Deficiency in Vitamin C disrupts the second stage of collagen synthesis in fibroblasts (hydroxylation of collagen) which results in petechiae, bruising, hemarthrosis.

Vitamin B₂ (riboflavin) deficiency – growth retardation, glossitis, conjunctivitis

Vitamin B₁ (thiamine) deficiency – Beri-Beri (polyneuritis)

Vitamin A (retinol) deficiency – Night blindness

Vitamin B₉ (folic acid) deficiency – macrocytic megaloblastic anemia

Explanation

Certain amino acids undergo decarboxylation that means the removal of their α-carboxyl group resulting in liberation of CO₂ and formation of biogenic amines. Biogenic amines are physiologically active substances such as hormones, neurotransmitters etc. decarboxylation of amino acids:

·        Tryptophan → Niacin → NAD⁺/NADP⁺

         Tryptophan → Serotonin →Melatonin

·        Histidine → Histamine

·        Glutamine → GABA

         Glutamine → Glutathione

Explanation

Substances absorbed into the bloodstream from the intestine pass through the liver, where toxins are normally removed. Many of these toxins (such as ammonia) are normal breakdown products of the digestion of protein. In hepatic encephalopathy (hepatic coma), toxins are not removed because liver function is impaired. Ammonia is produced by amino acid metabolism and intestinal urease-positive bacteria. In physiological conditions, it is mostly present as ammonium (NH₄⁺) in serum. The urea or ornithine cycle, which is fully expressed in the liver exclusively, serves to converts NH₄⁺ to urea prior to renal excretion and to maintain low serum concentrations. In hepatic coma, when the liver cannot remove toxins and urea cycle is not functional, all this occurs:

NH₃ + α-ketoglutarate → Glutamate

α-ketoglutarate is used up which leads to:

·        ↑glutamate → ↑GABA (inhibitory neurotransmitter)

·        Inhibition of citric acid cycle/tricarboxylic acid cycle; this causes impairment of ATP formation.

·        Inhibition of metabolism of amino acids (impairment of transamination reactions).

NH₃ + Glutamate → Glutamine

Glutamine is an amide of glutamic acid which provides a non-toxic storage and transport form of ammonia (NH₃). Ammonia increase synthesis of glutamine in brain. Accumulation of glutamine in brain results in elevation of osmotic pressure in nervous cells leading to brain edema.

                                    NH₃ + H⁺ → NH₄⁺

In blood ammonia (NH₃) is represented as ammonium ion (NH₄⁺). Accumulation of ammonium ion impairs transport of ions (Na⁺, K⁺) through cell membranes and failure of transmission of nerve impulse.

            Urea cycle takes place exclusively in the liver, so in hepatic coma, urea level is low. Glutamine toxicity in brain is dependent on increased ammonia concentration.

Bilirubin toxicity will most likely be related to increase hemolysis, which is not the case in this question. Histamine is a biogenic amine produced from the amino acid histidine.

Explanation

Vitamin B6 (pyridoxine): coenzyme forms – Pyridoxal phosphate (PALP)

                                                                         Pyridoxamine Phosphate (PAMP)

Components of pyridoxal enzymes used in transamination (e.g. ALT and AST); decarboxylation reactions, glycogen phosphorylase, transformation of tryptophan to Niacin (Vit B3), active transport of amino acids through the cell membrane, synthesis of cystathionine, heme, histamine and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine and GABA.

Explanation

The following steps occur in glycogen synthesis: glucose activation; initiation of glycogen synthesis; chain elongation; introduction of branch points. Glucose activation consists of the formation of UDP-glucose from glucose-6-phosphate, which is converted to glucose 1-phosphate by the enzyme phosphoglucomutase. Glucose 1-phosphate is then activated to UDP-glucose by glucose 1-phosphate uridylyltransferase; this reaction uses uridine triphosphate (UTP). UDP-glucose is the substrate in both the initiation step and the repetitive chain elongation steps. The enzyme responsible for the initiation and extension of the linear polymer is glycogen synthase.

Explanation

Explanation

Explanation

Emphysema: permanent enlargement of all or part of the respiratory unit. Causes include smoking cigarette (most common cause) and α₁-antitrypsin (AAT) deficiency. α₁-antitrypsin is a protease inhibitor; also referred to as α₁-proteinase inhibitor because it inhibits a wide variety of proteases (including trypsin as the name implies).

Explanation

Isoniazid is the hydrazide of isonicotinic acid and is a pyridine. Pyridine occurs in many important compounds including  azines and the Vitamins Niacin(B3) and Pyridoxine(B6). Therefore, isoniazid can be interfered with Vit.B3,B6 and even B1 metabolism by competing with them.

Isoniazid is a first line antituberculosis drug that inhibits the synthesis of mycolic acid. Vit B6 is needed for the transformation of tryptophan to Vit.B3.

Explanation

Polymerase chain reaction: molecular biology laboratory procedure used to amplify a desired fragment of DNA. Useful as a diagnostic tool. ELISA detect presence of either a specific antigen or a specific antibody in a patient’s blood sample.

Explanation

Nucleolar organizer is a chromosomal region around which the nucleolus forms. In humans, nucleolar organizer contain genes for rRNA (ribosomal RNA) clustered on the short arms of chromosomes 13, 14, 15, 21, and 22.

Explanation

Hepatic steatosis can occur when humans are deprived of choline.

Choline + Phosphatidic acid → Phosphatidylcholine (lecithin, PC). In the liver PC can also be synthesized from phosphatidylserine (PS) and phosphatidylethanolamine (PE), when free choline levels are low, because it exports significant amounts of PC in bile and as a component of serum lipoproteins (needed for fat metabolism)

PS → PE →→→ PC. 3 methylation reactions between PE and PC. S-adenosylmethionine is the methyl group donor. If choline, phosphatidylcholine or methionine is deficient, there will be abnormal phospholipid synthesis, oxidative damage caused by mitochondrial dysfunction, lipoprotein secretion (remember, if VLDL cannot be secreted it will be accumulated & cause fatty liver degeneration as seen in hepatic steatosis). PC is also a major lipid component of lung surfactant.

Explanation

GAD- Glutamate decarboxylase

GABA-T – GABA transaminase

SSADH- succinate semialdehyde dehydrogenase

Explanation

Sphingolipids are commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Certain complex glycosphingolipids (cerebrosides) are found predominantly in the brain and peripheral nervous tissue, with high concentrations in the myelin sheath. Gangliosides (most complex glycosphingolipids) are found primarily in the ganglion cells of the CNS, particularly at the nerve endings. Sphingolipidoses or disorders of sphingolipid metabolism, have particular impact on neural tissue e.g. Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay sachs disease. All of the diseases are autosomal recessive except Fabry disease which is X-linked and all can be fatal in early life.

Explanation

Glycogen storage diseases: 12 types, all resulting in abnormal glycogen metabolism and an accumulation of glycogen within cells. Type I (Von Gierke disease): findings – severe fasting hypoglycemia, ↑↑glycogen in liver, ↑blood lactate, ↑triglycerides, ↑uric acid and hepatomegaly. Deficient enzyme is glucose-6-phosphatase. It is autosomal recessive.

Deficiency of amyloid-1,6-glycosidase (Type III-Cori’s disease); deficiency of glycogen phosphorylase (Type V-McArdle’s; Type VI-Hers’)

Explanation

Congenital deficiency of homogentisate oxidase (homogentisic acid oxidase) in the degradative pathway of tyrosine to Fumarate → pigment-forming homogentisic acid accumulates (homogentisuria) in tissues. Autosomal recessive. Usually benign. Urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Phenylalanine → Tyrosine →→→ Homogentisic acid → Maleylacetoacetic acid

Explanation

Erythropoietic porphyria (Gunther’s disease): This disorder is due to a defect in the enzyme Uroporphyrinogen III cosynthase. It is characterized by:

* It is a rare congenital disorder caused by autosomal recessive mode of inheritance, mostly confined to erythropoietic tissues.

* The individuals excrete Uroporphyrinogen I and Coproporphyrinogen I which oxidize respectively to Uroporphyrin I and Coproporphyrin I (red pigments).

* The patients are photosensitive (itching and burning of skin when exposed to visible light) due to the abnormal porphyrins that accumulate. Porphyrins are accumulated in the teeth, bones and an increases amount are seen in the plasma, bone marrow, faeces, RBCs and urine.

* Increased hemolysis is also observed in the individuals affected by this disorder.

Explanation

α₂-macroglobulin and α₁-antitrypsin are protease inhibitors which can inhibit the pancreatic proteases and prevent further tissue protein breakdown. Immunoglobulin, Cryoglobulin – antibody; Ceruloplasmin – Copper; Transferrin – Iron; Haptoglobulin – hemoglobin; Interferon – released by cells in response to pathogens.

Explanation

Explanation

This is classic ornithine transcarbamylase deficiency. Most common urea cycle disorder. X-linked recessive. Interferes with the body’s ability to eliminate NH₃. Excess Carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway). Findings: ↑Orotic acid in blood and urine, symptoms of hyperammonemia. No megaloblastic anemia as seen in orotic aciduria – that’s why it is called secondary orotiic aciduria as used in the question.

Carbamoyl phosphate + Ornithine → Citrulline (urea cycle).

Carbamoyl phosphate is involved in 2 metabolic pathways: de novo pyrimidine synthesis and urea cycle. So, if the enzyme is deficient in urea cycle, all Carbamoyl phosphate will be channeled to de novo pyrimidine synthesis producing excess orotic acid.

Explanation

In the liver, fatty acids and amino acids are metabolized to acetoacetate and β-hydroxybutyrate (to be used in muscle and brain). In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. This cause a buildup of acetyl-CoA, which shunts glucose and free fatty acids (FFA) toward the production of ketone bodies. Breath smells like acetone (fruity odor). Urine test for ketones does not detect β-hydroxybutyrate.

Explanation

Ochronosis (Alkaptonuria): congenital deficiency of homogentisate oxidase (homogentisic acid oxidase) in the degradative pathway of tyrosine to Fumarate → pigment-forming homogentisic acid accumulates (homogentisuria) in tissues. Autosomal recessive. Usually benign. Urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Explanation

Vitamin B₂ (riboflavin): component of flavoproteins FAD and FMN, used as a cofactor in redox reactions (both aerobic and anaerobic dehydrogenases and oxidases). Flavine mononucleotide – FMN

                  Flavine adenine dinucleotide – FAD

[NAD – Vitamin B₃ (niacin, PP- pellagra preventing)].

Explanation

Collagen, most abundant protein in human body; organizes and strengthens extracellular matrix. Collagen contains Gly-X-Y (X and Y are proline or lysine). Glycine(Gly) makes 1/3 of collagen. Oxyproline (hydroxyproline) is a major collagen amino acid which enables it to be regarded as a marker that reflects the catabolism of collagen.

Paget disease of bone (osteitis deformans): localized disorder of bone remodeling caused by increase in both osteoclastic and osteoblastic activity.

Explanation

Electron transport chain: NADH electrons from glycolysis enter mitochondria via the malate-aspartate or glycerol-3-phosphate shuttle. FADH₂ electrons are transferred to complex II (at a lower energy level than NADH).

Inhibitors: complex I – Rotenone; complex III – Antimycin A; complex IV – cyanide, CO; complex V – Oligomycin. Cytochromes are electron carriers in the respiratory chain. They are arranged according to the values of their redox potentials in the following order: Cyt b; Cyt C₁; Cyt C; Cyt a; Cyt aa₃ . Cytochrome aa₃ or cytochrome oxidase is a terminal enzyme that transfers electrons directly to O₂.

Explanation

Pyruvate dehydrogenase complex: Mitochondrial enzyme complex linking glycolysis and citric acid cycle. The complex contains 3 enzymes that require 5 cofactors: Vit B₁, B_2, B_3, B_5, lipoic acid. Pyruvate → Acetyl-CoA.

The complex is similar to the α-ketoglutarate dehydrogenase complex (same cofactors, similar substrate and action), which converts α-ketoglutarate → Succinyl-CoA (CAC or TCA cycle). Arsenic inhibits lipoic acid. Findings: vomiting, rice-water stools, garlic breath.

Explanation

This is a classic description of gout. The end product of the purine nucleotides catabolism in humans and other primates is uric acid (urate) which is excreted in urine. Allopurinol and febuxostat inhibits Xanthine oxidase (XO). Hypoxanthine and Xanthine which is more soluble is excreted in urine. Purine nucleotides (adenine and guanine).  AMP – Adenosine monophosphate; GMP – Guanosine monophosphate

Pyrimidine (thymine, Uracil, cytosine); catabolism of thymine and uracil gives urea, while catabolism of cytosine gives β-alanine.

Explanation

Peroxidase is a large family of enzymes and its optimal substrate is hydrogen peroxide e.g glutathione peroxide.

Catalase is found in organisms exposed to oxygen. It decomposes hydrogen peroxide to water and oxygen. H₂O₂ → H₂O + O₂

·        Hydroxylase: adds hydroxyl group (-OH) onto a substrate.

·        Oxygenase: oxidizer

·        Oxidase: oxidation-reduction reactions.

Explanation

Pancreatic juice contains enzymes that can digest all food substances. α – amylase: carbohydrates; Lipase: fat; Proteases: protein. All others do not have all the enzymes needed to digest all 3 major food substances.

Explanation

Ethanol metabolism ↑NADH/NAD⁺ ratio in liver, causing:

·        Pyruvate → Lactate (lactic acidosis).

·        Pyruvate → Lactate ; Oxaloacetate → malate ; both reations increase NADH/NAD⁺ ratio.

Prevents gluconeogenesis which results in fasting hypoglycemia.