biochemistry points (from uworld and fa)

BIOCHEMISTRY POINTS (FROM

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1. DNA binding domain/protein include ………………transcriptional factors ( MYC, CREB) , steroid

receptors ( cholesterol, progesterone, aldosterone ) , thyroid hormone receptor, fat soluble vitamin

receptors and DNA transcription and translation proteins

2. In sickle cell anemia, sickling is promoted by……………………. Low blood volume, increase acidity,

low oxygen level, increase 2,3BPG (normally 2,3BPG bind to HB and decreases the HB and o2 affinity,

facilitating o2 release at tissue level. So in 2,3 BPG depletion, the affinity of HB for o2 increase, leading

to left shift of thee dissociation curve. Thus o2 uptake by HB increase and sickling decreases )

3. Thiamine requiring enzymes …………………………. PDH, Alpha-ketogultarate dehydrogenase (TCA

cycle), Transketolase (HMP Shunt) and branched chain keto-acid dehydrogenase. In chronic

alcoholics, alcohol dehydrogenase and aldehyde dehydrogenase consume NAD and lead to increase

NADH/NAD ratio. This inhibits all pathways requiring NAD. Also alcoholics are deficient in Thiamine.

if they give you the diagram of any pathway and ask you which step will be inhibited , just look the

pathway and check thiamine dependent enzyme .This is because in alcoholics thiamine is deficient so

thiamine dependant enzyme won’t work

4. RAS gene ……………………is active only when bound to GTP and inactive when bound to GDP

5. P50 ……………..refers to partial pressure of o2 at which HB is 50% saturated. HB with high o2 affinity

have decreased P50 that is represented by left shift of o2 disassociation curve. This reduced the

ability to release o2 to tissues, leading to hypoxia which stimulated EPO. This lead to compensatory

erythrocytosis


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6. Marfan syndrome ……………….is due to defect in fibrillin 1, an extracellular glycoprotein that form

sheath around elastin. It is abundant in zonular fibers of lens, periosteum and aortic media. Aortic root

dilation with rupture is the most common cause of death

7. DNA polymerase 1 …………………...during bacterial DNA replication, DNA polymerase 1 functions to

remove RNA primers via its 5-3 exonuclease activity and replace them with DNA via 5-3 polymerase

activity. DNA polymerase 1 is the only bacterial DNA polymerase that has 5-3 exonuclease activity.

8. Initial HB form by fetus in utero is …………………called Gower Hb ( two zeta and two epsilon chain ),

produced largely by embryonic yolk sac. Within few weeks fetal liver start synthesizing HBF (two

alpha and two gamma chains), which is the major HB during the last month of gestation and during

first few weeks of post natal life, which is then replace by adult HBA. In homozygote B-thalasemia (

thaalsemia major ), patients are asymptomatic at birth due to the presence of gamma chain and HBF

9. Steroid producing cells contain …………………..a well developed smooth ER

10. RER ……………...plays an important role in synthesis and modification of targeted proteins, including

secretable polypeptide hormones. Some of the syndromes due to overproduction of these polypeptide

hormones by RER include ( SIADH, insulinomas, zollinger elson syndrome and putitary adenoma)

11. Cores disease…………………a disbranching enzyme deficiency which involves both liver and muscle .

classical finding is abnormal glycogen with very short outer chains .

12. Hyper ammonia ………………. normally astrocytes regulate neuronal transmission by taking up

glutamate present in the synapse, preventing excessive neuronal excitation. Then via the action of

glutamate synthase the glutamate undergoes reaction with ammonia to form glutamine. Glutamine is


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then released by astrocytes and taken up neurons where it is converted back to glutamate to be used

as neurotransmitter (GLUTAMATE-GLUTAMINE CYCLE). When excess ammonia is present, it cross

BBB and cause increased production of glutamine and cause its accumulation in astrocytes . Thus,

decrease the amount of glutamine available for conversion to glutamate , resulting in disruption of

excitatory neurotransmitter

13. Mitochondrial DNA ………………most common non-nuclear DNA found in eukaryotic cells and is

maternally derived. It encodes for about 14 protein which are involved in oxidative-phosphorylation,

and some also encode for ribosomal and transfer RNA, needed for mitochondrial protein synthesis.

Mitochondria can be easily identified in electron microscope via its double membrane and wavy cristae.

14. In phenylketonuria patient ………………….tyrosine is the essential AA because phenylalaine

hydoxylase deficiency in these patients block conversion of phenylalanine to tyrosine. Also high

phenyalanine inhibit the tyrosinase enzymes which is responsible for production of melanin so that is

why these patient has fair skin, eyes, and also hypopigmentation of cetecholaminergic brain nuclei

(substantia nigra, locus ceruleus and dorsal vagal neuclei)

15. Mapple syrup urine disease ………………. deficiency of branched chain alpha ketoacid

dehydrogenase result in blocked degradation of branced amino acid (isoleucine and valine to

propanyl coA and leucine to actyl co-A is blocked). Branched chain alpha ketoacid dehydrogenase

(also PDH and alpha ketogultarate dehydrogenase) require 5 cofactor: Thiamine, lipoid acid ,

coenzyme A, FADH2 and NADH . URINE in this disease smell like syryp/burnt/caramelizing sugar.


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Some patients with MSUD response to thiamine supplement. Total restriction on isoleucine ,leucine

and valine

16. Gluconeogenesis …………………...Acetyl co A stimulate the first step in gluconeogeneis by

stimulating the enzyme pyruvate carboxylase.

17. snRNA ……………it is synthesized by RNA polymerase 2 in nucleus and complex with specific

protein to form snRNP. snRNP is an essential component of splicesome whose function is to remove

intron and convert primary transcript (pre mRNA ) to mature RNA . PATIENT with SLE has

autoantibodies against snRNP called anti smith antibody

18. Niemann-pick disease……………deficiency of sphingomyelinase which cause accumulation of

sphingomeylin. Clinical findings are neurodegenration and hepatospleomegaly, foam cell and cherry

red spot in macula. (In tay sach disease also neurodegeneration and cheery red spot occur but

hepatosplenomegaly is absent)

19. Mitochondaria …………..necessary for 1st and final 3 steps of heme synthesis. If erythrocyte loose

mitochondria, they lose the ability to generate heme and therefore HB

20. Haldane effect (LUNG) …………………-deoxygenated blood enters alveolar capillaries………. rise in

pO2 increases binding of O2 to hemoglobin (left shift) and causes release of H+ and CO2 from

hemoglobin………………HCO3- shifts back into erythrocytes in exchange for chloride, carbonic

anhydrase converts H+ and HCO3- back into CO2 + H2O …………. CO2 is then excreted through lungs

21. Bohr effect (PERIPHERAL TISSUE) ………………...increase in PCO2 enhances release of O2 from

hemoglobin (right shift). Tissue releases CO2 - majority is converted by erythrocyte carbonic


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anhydrase to HCO3- + H+………………HCO3- shifted out of erythrocytes for Cl- in plasma, H+ remains in

erythrocytes……………….H+ buffered by histidine residues on Hb and in process helps stabilize the

deoxygenated form of Hb and decreases affinity for O2

22. Galactokinase deficiency ……………. result in build of up of galactose, which is converted to

galactitol by aldose reductase enzyme. Galactitiol accumulates in lens of the eye giving rise to

childhood cataract

23. Homocystinuria ………….is caused by deficiency of cystathionine deficiency. Affected

individuals has marfanoid habitus, ectopic lentis and developmental delay. Morbidity is due to

thromboembolism. Majority of the patient responses to vit b6 supplements. ALSO, due to enzyme

deficiency cysteine can’t be formed, cysteine supplement should be added to these patient diet.

24. Folate deficiency ………………normally folate derivatives are crucial for synthesis of nucleic acid,

particularly thymine but also purines. In presence of folate active form (THF) which is formed by

dihydrofolate reducatse from dihydrofolate , the thymidylate synthase converts dUMP to dTMP (

DNA synthesis ). In folate deficiency, synthesis of nucleic acid won’t happen,particulary the

formation of dTMP. This lead to defective DNA synthesis that cause increase apoptosis of homeopathic

stem cells and megaloblastic anemia. Thymidine supplementation bypass this enzyme and can

reduce eryhtroid cell apoptosis

25. Zellweger syndrome ……………AR condition. Disorder of peroxisome biogenesis due to mutated

PEX gene. Peroxisome won’t be able to do B-oxidation of LCFA. Thus LCFA accumulate in neuronal cell


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membrane leading to neurologic deficits like hypotonic, seizures and developmental delay. Also

craniofacial abnormalities and hepatomegaly can occur

26. G6PD deficiency………………cause hemolytic anemia and jaundice secondary to oxidative stress

due to lack of NADPH, which is required by glutathione reductase to convert oxidized glutathione to

reduced glutathione. Glutathione reductase deficiency will have the same clinical presentation like

G6PD. This is because its absence results in ability to utilize NADPH to reduce glutathione

27. Essential fructosuria ………….AR condition due to defect in fructokinase. Fructose similar to

glucose and galactose is a reducing sugar and can be detected by CU reduction test, which

nonspecifically detect the presence of reducing sugar. A urine dipstick however uses glucose oxidase

to detect the presence of urinary glucose and will not test positive in presence of fructose or

galactose. Also in this disorder the hexokinase become the primary pathway that convert fructose

to F-6-PO4

28. RT-PCR……………..detects and quantifies mRNA levels in a sample. Uses reverse transcriptase to

create complementary DNA template that is amplified via standard PCR procedure. RT-PCR can be

used to diagnose CML by identifying mRNA transcript containing both BCR and ABL exons in affected

cells

29. Dihydrobiopetrin reductase deficiency……………...This enzyme is used for conversion of BH2 to

BH4, which is then used as cofactor by phenylalanine and tyrosine hydroxylase. In phenylketonuria

patients although tyrosine supplementation can lead to normal catecholamine production as tyrosine


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hydroxylase is working fine but since BH4 is deficient, the enzyme won’t work properly, leading to

downstream deficiency of epinephrine, norepinephrine, dopamine and serotonin

30. PDH complex deficiency …………. Patients are unable to convert pyruvate to acetyl co A and

instead it is converted to lactic acid leading to lactic acidosis. In these patient, ketogenic AA like

leucine and lysine can provide energy in the form of acetyl co A (which can form ketone bodies)

without increasing lactate production. Glycogenic AA should not be given to these patients as their

metabolism produce pyruvate or TCA cycle intermediates, which can be converted to glucose via

gluconeogenesis

31. Ornithine transcarbamylase deficiency …………..this enzyme cause conversion of carbamoyl

phosphate+ ornithine to citrulline, which is one of the step in urea cycle . Deficiency leads to

accumulation of cabamoyl phosphate which lead to pyrimidine synthesis. As an intermediate

product in this pathway, the carbomyl phosphate is converted to orotic acid which accumulates,

leading to orotic acid in urine. Patient also has hyperammonemia which cannot be seen in classical

orotic aciduria caused by deficiency of uridine monophosphate synthase

32. Southwestern blot……………identifies DNA binding proteins such as transcription factors (c-Jun

and c-Fos), nuclease and hsitone.

33. Ubiquitin …………….is a protein that undergoes ATP dependent attachment to other protein,

labeling them for degradation by proteasome in to small peptides. Impairment of ubiquitin-

proteasome system can contribute to the development of neurodegenerative disorder, including

Parkinson’s and Alzheimer’s disease


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34. Leptin ………………protein hormone produced by adipocytes in proportion to the quantity of fat

stored. It acts on the arcuate nucleus of hypothalamus to inhibit production of neuropeptide Y

(decreasing appetite) and stimulate production of alpha-MSH (increasing satiety). Individuals who

have Mutation in genes encoding leptin receptors result in ineffective leptin signaling. As a result it

leads to hyperphagia and profund obesity. As leptin production will be normal in these individuals,

leptin levels are elevated due to increased lipocyte mass. However, those who has mutation in leptic

production also become hyperphagic and obese but their leptin level will be low.

35. JAK-STAT pathways ……………. used by GH, cytokines (interferons) and hematopoietic growth

factors (erythropoietin, G-CSF)

36. Integrins ………………. adhesion of cells to ECM involves integrin mediated binding to fibronectin,

collagen and laminin.

37. Hormone sensitive lipase…………………...degrades TG stored in adipocytes to FFA and glycerol.

During fasting , the glycerol can be used as a carbon source for gluconeogenesis and the FFA can be

used for ketone body formation

38. Fibrates (fenofibrate, gemfibrozil) ……………PPAR-gamma, leading to up regulation of

lipoprotein lipase. This lead to increased oxidation of FA. However, this drug also inhibits cholesterol

7-alpha hydroxylase, which catalyze the rate limiting step in bile acid synthesis. The reduced bile acid

production leads to decreased cholesterol solubility in bile and favor the formation of cholesterol

gallstones (yellow to pale gray and hard)


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39. Pigment stone…………….are composed of calcium salt of unconjugated bilirubin that are soft and

dark brown in color. They typically arise secondary to bacterial infection (E. coli), helimenthic

infection ( Ascaris, clonorchis sinensis), which cause the release of beta-glucuronidase by inujured

heptocytes and bacteria. This enzyme hydrolyzes bilirubin glucuronides to unconjugated bilirubin.

40. Myoglobin …………………...the p50 of HB (tetrameric structure) is 26mmhg, while the p50 of

myoglobin (monomeric structure) is 1mmhg, which indicates that myoglobin has higher affinity for

o2 then Hb. It also show that instead of sigmoid shape curve of HBA , the myoglobin represent the

hyperbolic curve due to not experiencing heme-heme interactions bcz of momoeric/single heme group

41. Pyridoxine (vit b6) ………………….is necessary for transamination and decarboxylation of AA

for gluconeogenesis and for other biochemical processes. Transamination reaction typically occur

between AA and ketoacids. The aminio group is transferred from AA to keto group, and the alpha

ketoacid therefore become AA. Eg:…..glutamate(AA) react with oxaloaccetate( alpha-ketoacid) to

form aspartate ( resulting AA) and alpha-ketoglutarate( the resulting keto acid ).

42. Substrate for gluconeogenesis ……………in insulin deficiency the hormone sensitive lipase

becomes active and cause break sown of TG to glycerol and FFA. Glycerol in liver is converted by

glycerol kinase to glycerol 3-po4. Glycerol 3-po4 is then converted to DHAP by glycerol 3-po4-

dehydrogenase which can be used to produce glucose via gluconeogenesis

43. Alanine…………major AA responsible for transferring nitrogen to liver for disposal. During the

catabolism of protein, alanine in produced which transfer its amino group to alpha-ketogultarate


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forming glutamate. Glutamate is processed in the liver to form urea, the primary disposal of nitrogen

in humans.

44. Hartnup disease………….AR disorder due to inactivating mutation in neutral AA transporter

(tryptophan) in proximal renal tubular cells and on enterocytes, leading to aminoaciduria and

decrease absorption from gut. Thus decrease tryptophan lead to less niacin. Patient comes with

pallegra like symoptoms. Diagnosis can be confirmed by detection of excessive neutral AA in urine.

Treatment with niacin and protein diet.

45. RMP …………………..high K efflux and some Na influx are responsible for the value of RMP, which is

typically around -70mv

46. Alkaptonuira ………………congenital deficiency of homegentisate oxidase in the degradative

pathway of tyrosine to fumarate, which means that homegentisic acid can’t be converted to fumarate.

This will cause accumulation of homegentisic acid that binds with collagen, leading to ochronosis

(bluish-black connective tissue, ear cartilage and sclera and urine turend black on prolong exposure

to air.

47. Urea cycle disorders…………………ornithine transport into mitochondria is necessary for proper

working of urea cycle, which is the major pathway for removal of nitrogen generated by excess break

down of AA. Urea cycle defect causing accumulation of ammonia, leading to neurological changes.

Treatment is dietry restriction on proteins or medication (phenylacetate) can also work.


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48. FISH…………………can identify specific chromosomal translocation, duplication or deletion using

a ss complementary DNA segment that is tagged with radio tracer. FISH is rapid, highly sensitive and

specific and can be used on tissue with low mitotic rates.

49. Lesch-Nyhan syndrome……………defective purine salvage due to absent HGPRT enzyme, leading

to increased degradation of hypoxantine and guanine to uric acid. This increases the demand of DE

novo purine synthesis, which should be accomplished by increasing PRPP aminotransferase activity that

cause conversion of PRPP to 5-phosphoribosymamine which can be then converted to IMP, AMP &

GMP. Patient presents with intellectual diability , self-mutilation , aggression , hyperurecemia ,

dystonia and macrocytosis

50. LDH deficiency and exercise…………..during glycolysis, glyceraldehyde 3-po4 is converted to 1.3

biophospho glycertae. This enzyme reduces NAD to NADH. NAD is present in limited amount in most

cells and it must be regenerated in order to continue glycolysis. In anaerobic condition (exercise),

pyruvate generated via glycolysis is converted to lactate via LDH, generating NAD, which can be used

for glycolysis. In patient with LDH deficiency, glycolysis is inhibited in exercising muscle as muscle

cell won’t be able to generate NAD.

51. Fabrys disease……………. deficiency of alpha-galactosidase A, lead to accumulation of ceramide

trihexoside . Present with triad of peripheral neuropathy, angiokeratoma and hypohidrosis.

Complications include……. progressive renal failure, LVH and TIA/STROKE

52. Maturity onset diabeties of young (MODY)………Glucose enter pancreatic B cell via GLUT-2

transporter and it is metabolized to G-6-PO4 via glucokinase enzyme. It then enters the glycolysis


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and generate ATP. Increase ATP cause closure of ATP sensitive K channels. Depolarization of beta

cells triggers opening of voltage gated Ca channels and thus influx of Ca cause insulin release.

Glucokinase serve as glucose sensor of beta cells in controlling insulin release. Mutation in

glucokinase results in condition in which higher glucose is required for secretion of insulin, leading

to maturity onset diabetes in young.

53. Riboflavin …………is the precursor of coenzyme FMN/FAD. FAD participates in TCA and ETC by

acting as an electron acceptors of succinate dehydrogenase, which convert succinate to fumarate.

54. Niacin……………is precursor of NAD/NADP, two important co factors for many dehydrogenase (

isocitrate dehydrogenase ) and reductase enzymes.

55. Heme oxygease………………. convert heme to bilivirdin, a pigment that cause the greenish color to

develop in bruises several days after injury.

56. G6PD……………enzymes responsible for the major source NADPH in HMP pathway. The NADPH

generated can be used for reducing glutathione and biosynthesis of cholesterol, FA and steroids.

57. Elastin …………….is rich in non-hydroxylated proline, lysine and glycine residue VS the

hydroxylated residue of collagen. Synthesis pathway is same like collagen

58. ARGINASE DEFICIENCY………………….. is a urea cycle enzyme that produces urea and ornithine

from arginine?.Deficiency lead to progressive spastic diplegia, growth delay, and abnormal

movements, Treatment includes an Arg-free, low protein diet

59. Acute intermittent porphyria ……………………autosomal dominant condition that cause

neurologic symptoms ( tingling, difficulty concentrating ) and nonspecific abdominal pain. Attacks are


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due to accumulation of porphobilinogen and aminolevulunic acid due to PBG deaminase deficiency

combined with ALA synthase induction (typically due to certain medications, alcohol use, or a

low-calorie diet). Management with glucose or hemin, that inhibits ( down regulate ) ALA synthase

( rate limiting step in heme synthesis ) activity

60. Acidosis ……………….stimulate renal ammoniagenesis , a process by which renal tubular epithelial

cells metabolize glutamine to glutamate, generating ammonium that is excreted in urine and HC03

that is absorbed in blood. This process is responsible for vast majority of renal acid excretion in

chronic acidotic state.

61. Porphyria cutanea tarda…….deficiency of uroporphyrinogen decarboxylase enzyme is the heme

synthesis pathway, lead to accumulation of uroporphyrin. Present with blistering cutaneous

photosensitivity and hyperpigmentation. It is aggravated by alcohol consumption. Treatment is

phlebotomy, sun avoidance and anti-malarial ( hydroxychloroquine)

62. 2,3BPG…………….it is produced from 1,3BPG by the enzyme phosphoglycerate mutase. This

reaction by pass ATP generating step in glycolysis, causing no net gain in ATP

63. Fructose ……………. dietary fructose is phosphorylated in the liver to F-1-PO4 and is rapidly

metabolized because it by passes the PFK-1, a rate limiting step in glycolysis. Other sugars like

galactose, glucose and mannose enter glycolysis prior to PFK-1 and as result are metabolized slowly

64. FA oxidation…………in well feed state,the abundance of ATP in hepatocytes inhibit isocitrate

dehydrogenase, leading to accumulation of citrate in the mitochondaria. Citrate is then transferred to

cytosol via citrate shuttle and cleaved by ATP-citrate lyase to form acetyl coA. Also high citrate level


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cause upregulation of acetyl coA carboxylase which cause conversion of acetyl coA to malonyl coA (FA

synthesis). B-oxidation of FA occur in mitochondria and as FA are impermeable due to negative

charge so they use carnitne shuttle. Malaonyl coA inhibit carnitineacyl transferase ,prventing the

transfer of acyl group to mitochondaria .This inhibit the further breakdown of newly synthesized FA

65. Isonazoid…………..inhibit the enzyme pyridoxine phosphokinase ,which normally convert

pyridoxine to its active from pyridoxil 5-po4. Pyridoxine is a cofactor for gamma aminolevulunic

acid synthase, the enzyme that catalyze the rate limiting step in heme synthesis. Deficieny of

pyridoxine can lead to sideroblastic anemia (ringed sideroblast that can be seen on Prussian blue stain

BM aspirate.

66. Phenylethanolamine-N-methytransferase………………. responsible for conversion of NE to

epinephrine

67. Ketone bodies…………………..during prolong fasting ketone bodies are produced in liver and can be

used as an energy source in the mitochondria `of peripheral tissues. Muscle , renal cortex and brain

use ketone body but erythrocyte can’t use it because of lack of mitochondria,

68. Mitochondria……………B-oxidation of FA, TCA cycle, and carboxylation of pyruvate(

gluconeogenesis) occur in mitochondria

69. Cytosol…………..FA synthesis , glycolysis and HMP shunt occur in cytosol

70. mcArdle disease…………………deficiency of myophosphyrylase, which lead to decrease break

down of glycogen during exercise, resulting in poor exercise tolerance, muscle cramps and

rhabdomyolysis


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71. Free ribosomes…………remain floating in the cytosol throughout protein synthesis. They are

responsible for translating protein found within cytosol, nucleosol, peroxisome matrix and nuclear

enbounded mitochondrial protein

72. Attached ribosomes………….binds to RER after translation begins. They are responsible for

synthesis of secretory proteins, the integral membrane protein of nucleus and cell membrane and

protein with ER, golgi network and lysosomes.

73. Primase………….it is a DNA dependent RNA polymerase that incorporate short RNA primers in to

replicating DNA

74. Protein targeting……………is the process by which protein with different intra and extracellular

fates reach their destination. Protein destined for lysosome require phosphorylation of specific

mannose residue to ensure proper transit through the Golgi apparatus.

75. Biotin……………….is required as cofactor for pyruvate carboxylase ( cause conversion of puruvate

to OAA………gluconeogenesis), Acetyl coA carboxylase ( cause conversion of Acetyl coA to Malonyl

coA……..FA synthesis), propionyl coA carboxylase ( cause conversion of propionyl coA to methy

malonyl coA………fatty acid oxidation)

76. Zinc finger motifs …………………composed of chains of AA bound together around zinc atom via

linkages with cystidine and Histidine residues. They recognize specific DNA sequences and are used

by many transcription factors to bind DNA and alter activity of target genes. Intracellular receptors

that bind steroids, thyroid hormone, and fat soluble-vitamins act directly as transcription factors and

contain zinc finger binding domains


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77. Primary carnitine deficiency…………...impairs FA transport as acyl-carnitine (carnitine shuttle)

from cytoplasm to mitochondria. The mitochondria therefore can’t do B-oxidation of LCFA to acetyl

coA, the carbon substrate for TCA. Thus cardiac and skeletal muscle cannot generate ATP from FA,

leading to muscle weakness, cardiomyopathy and the liver is unable to synthesize ketone bodies(

manifest as hypoketotic hypoglycemia

78. Amino acid change in HbS………………….Val to Glutamic acid at 6th AA of beta global chain,

promotes hydrophobic interaction among Hb molecules and results in HBS polymerization and

erythrocyte sickling

79. Amino acid change in HbC…………….glutamate to lysine. Because lysine is + charged there is no

hydrophobic interaction between HB molecules and no polymerization/sickling. However, these

positive charge of lysine cause HbC to have decreased mobility on electrophoresis.

80. G-protein coupled receptors………………bind glycoprotein hormone (TSH, LH, FSH) contain 3

major domains. Extracellular domain………responsible for ligand binding, Transmembrane domain,

and an intracellular domain coupled with heterotrimeric G protein. The transmembrane domain

is composed of alpha helices with hydrophobic AA residue(ALANINE, VALINE,

LEUCINE,PHENYLALANINE, TRYPHTOPHAN, PROLINE, GLYCINE) , which help to anchor the protein to

the phospholipid bilayer of cell membrane.

81. Glycogen degradation……………glycogen stored in liver is used to provide energy or glucose during

the period of fasting whereas glycogen stored In muscle provide energy during muscle contraction.


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In liver, glycogen phosphorylase is activated via binding of epinephrine and glucagon to Gs-coupled

receptors, which increase cAMP concentration and cause phosphorylation of glycogen phosphorylase.

As skeletal muscle lack glucagon receptors, still to some extent can be phosphorylated in response to

epinephrine mediated raise in cAMP concentration. However, intracellular Ca is more powerful

activator of muscle PK. Ca is released from sarcoplasmic reticulum following neuromuscular

stimulation

82. Propionic acedemia…………………. deficiency of propionyl-CoA carboxylase which lead to

elevated level of propionyl-CoA. As a result, excess propionic acid builds up in the blood , leading to

sever metabolic acidosis, leading to ketosis and hypoglycemia. As (Valine, Odd-chain FA,

Methionine, Isoleuucine, Threonine……….VOMIT) metabolize to propionyl-C0A, they should be

avoided in diet

83. Methymalonic acid academia……………is an organic academia due to deficiency of

methymalonyl-coA-mutase enzyme, which lead to build up of methymalonic and propionic acid,

leading to metabolic acidosis. Hypoglycemia result from overall increase in metabolic rate which cause

the formation of ketone bodies to compensate, leading to excess ketone bodies formation. Finally

organic acids buildup and inhibit urea cycle,leading to inc ammonia level. Diagnosis is confirmed by

increase urinary methylmalonic acid and propionic acids.

84. Familial erythrocytosis ………………….due to B-glolbin mutation resulting in reduced binding of

2,3BPG. 2,3BPG binds strongly to deoxy-Hb in a pocket form between the 2 Beta chains. The Hb

2,3BPG binding pockets contain positively charged AA (histidine, lysine) that attract the negatively


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charged PO4 group in 2,3BPG. This binding reduces the O2 affinity of HB allowing more O2 to diffuse

in to tissues. Mutation that decrease positive charge of the binding sites cause HB A to resemble HBF,

which binds o2 with a higher affinity due to its inability to interact with 2,3BPG.

85. Gluconeogenesis ……………..during gluconeogeenesisis, OAA is converted to phosphoenol

puruvate by enzyme PEP carboxylase which requires GTP as co factor. This cofactor comes from TCA

cycle where succinyl coA is converted to Succinate by succinyl-coA synthetase ,generating GTP

86. Stress hyperglycemia………………. transiently elevated blood glucose level in the context of fever

illness( sepsis, burn , hemorrhage) in patients without existing DM. Cortisol and epinipheren release

in stress leading to glycogenolysis and gluconeogenesis

87. The speed of HB movement during gel electrophoresis is …………HBA>HBS>HBC

88. OROTIC ACIDURIA …………..is due to defect in uridine 5, mono-po4 synthase enzyme so that

orotic acid cannot be converted to UMP. Patient present with large amount of orotic acid in urine

along with megaloblastic anemia due to defect in DNA syntheses, without defect in replication, leading

to large red cells. Treat these patients with URIDINE to bypass the step bcz uridine can be converted

to UMP via nucleoside kinases. Done confuse this with ornithine transcarbamylase deficiency in

which along with high orotic acid an increase ammonia level will be present

biochemistry points (from uworld and fa)

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