Biochem - S Flashcards
What type of bonds stabilize 1° protein structures
Peptide Bonds
What type of bonds stabilize 2° protein structures (alpha helix vs. Beta sheets)
Hydrogen Bonds
What type of bonds stabilize 3° protein structures (4)
Ionic /Hydrophobic /Hydrogen /Disulfide Bonds
Tertiary = overall shape after compact folding of secondary structure
Describe Disulfide Bonds
Strong Covalent bonds between 2 cysteine residues within the same polypeptide chain –> prevents denaturation
After 12-18 hours of fasting, ____ becomes the main source for blood glucose. Recall the reaction that ends with Glucose vs. energy.
Gluconeogenesis;
Pyruvate —(pyruvate carboxylase)–> Oxaloacetate —(PEP carboxykinase) —> PEP
ActetylCoA upregulates pyruvate carboxylase
What are [Transmembrane Domains] made of and what is their function?
[Alpha helices made with Hydrophobic Amino Acids]; anchors Integral proteins to phospholipid bilayer
[Methylmalonic Acidemia] MOD
Organic acidemia due to deficiency of methylmalonyl-CoA mutase
[Methylmalonic Acidemia] Labs (3)
- HyperAmmonemia
- Ketotic hypOglycemia
- INC Urine Proprionic Acid - metabolic acidosis
[Familial Dysbetalipoproteinemia Type 3] Mode of inheritance
auto recessive
[Familial Dysbetalipoproteinemia Type 3] MOD
Defects in [ApoE3 and E4]–> DEC clearance of chylomicrons & VLDL remnants
[Familial Dysbetalipoproteinemia Type 3] Clinical Presentation (3)
- Xanthomas
- Atherosclerosis
- INC Cholesterol & Triglyceride
Which Vitamin deficiency is [Egg White Avidin] associated with and how does this present (3)?
Having No Bio makes me MAD!
[Biotin B7]; [Myalgia(lactic acidosis)] + Anorexia + Dermatitis
(Egg White Avidin Avidly Binds [Biotin B7])
1 gram protein = ___ calories
[1 gram protein] = [4 calories]
1 gram fat = ___ calories
[1 gram protein] = [9 calories]
Spliceosomes require ____ to Function. What is their function and what are they made by?
snRNPs (small nc. ribonucleaic acid - made by RNA Pol 2 in nucleus)
Remove introns containing [GU at 5’] and [AG at 3’] from pre-mRNA –> Forms [Mature mRNA Exons]
snRNPs are targeted by SLE Smith Ab
How is Ca+ associated with Glycogen Degradation in Skeletal m.
Sarcoplasmic Retic. releases Ca+ –> Activates [Phosphorylase kinase] –> Stimulates Glycogen phosphorylase —> Glycogenolysis
Where does Vitamin __ hydroxylation of proline and lysine of collagen occur?
Vitamin C; Rough ER
Vitamin C deficiency –> Scurvy
Xeroderma Pigmentosum defect
defect in DNA excisional repair; exacerbated with UVB radiation
Xeroderma Pigmentosum Clinical Presenatation at:
A: 1 yo (4)
B: Later in life
Dry Pigmented Skin
- 1 yo: Scaling + Erythema + [Lentigo on face] + Hyperpigmentation
- Later in life: Skin Atrophy + Telangiectasia + CA
Xeroderma Pigmentosum Mode of inheritance
auto recessive
What 2 mechanisms regulate the Lac Operon
- Repressor binding to operator locus = negative regulation
- cAMP-CAP binding upstream of promoter = positive regulation
What happens when mutations impair binding of repressor to the operator locus?
Constitutive Expression of Lac Operon
Describe Alternative Splicing
Exons of a gene are reconnected during post-tx processing – > different mRNA –> different proteins
Is Alternative Splicing a normal function of Eukaryotes? Why or why not?
Yes; INC biodiversity of proteins
What is HgbC caused by and how does it manifest?
Missense mutation resulting in Glutamate being replaced by Lysine (less negative charge) in beta globin chain –> milder form of sickle cell
[Spinal Muscular Atrophy] MOD
SMN1 mutation –> impaired assembly of snRNPs in LMN –> Flaccid paralysis
Transamination occurs between ____ and ____. Which molecule serves as a cofactor for transamination and decarboxylation
Transamination occurs between [amino acids] and [a-keto acid]. [Pyridoxine B6] = transamination cofactor
What is the the Wobble Hypothesis
First 2 nucleotide positions on mRNA codon require traditional base pairing, but the [third wobble nucleotide] may undergo nontraditional base pairing –> more than 1 codon can code for an AA
How does [Pyruvate Kinase] deficiency cause Hemolytic anemia and Splenomegaly
Failure of Glycolysis –> insufficient ATP to maintain RBC structure –> [splenic red pulp hyperplasia] to remove these deformed RBC
[Tetrahydrobiopterin BH4] is a cofactor for the synthesis of what compounds? (3)
Tyrosine
Dopapmine
Serotonin
What Dz occurs from [Tetrahydrobiopterin BH4] deficiency? MOD
(PKU) Phenylketonuria; Dihydropteridine Reductase becomes deficient w/out cofactor –> Inability to convert Phenylalanine –> Tyrosine
Phenylketonuria tx (2)
- low phenylalanine diet
- BH4 supplementation
Which DNA Polymerase has exonuclease activity and what is the exonuclease function (2)
[DNA Pol 1 and 3] has [3 —> 5 exonuclease activity] + [5–>3 Polymerase] activity
Exonuclease removes RNA primer and repairs DNA sequences
What type of relationship does TNFa have with Insulin receptors?
TNFa Phosphorylates [serine & threonine AA of insulin receptors and their subtrates] –> Insulin Resistance
Catecholamines/Glucocorticoids/Glucagon also do this
HyperHomocysteinemia is due to mutations in ____ (3)
6 / 9 / 12
[Pyridoxine B6] vs. [Folate B9] vs. [B12]
HyperHomocysteinemia Manifestations (3). INC risk for what?
- Marfanoid Habitus
- Ectopia Lentis
- Developmental Delay
INC RISK FOR THROMBOEMBOLISM
Describes Homocysteine metabolism
[Pyruvate Dehydrogenase Deficiency] causes ____ and ____ clinically. MOD
Lactic Acidosis ; Neuro defects
Inability to convert Pyruvate –> AcetylCoA –> shunting of Pyruvate to Lactic Acid during oxidative phosphorylation
[Pyruvate Dehydrogenase Deficiency] Tx
[Exclusive Ketogenic Amino Acids (Lysine vs. Leucine)]
since these will provide AcetylCoA w/out INC lactate
Describe the path for Pyruvate –> Energy
Describe the path for Pyruvate –> Glucose
AcetylCoA upregulates [Pyruvate Carboxylase]
Glycolysis, Fatty Acid Synthesis and Pentose phosphate all occur in what part of the cell?
Cytosol
B-oxidation, TCA and Pyruvate Decarboxylation all occur in what part of the cell?
Mitochondria
What is Transketolase
[Pentose Phosphate pathway] enzyme that uses [Thiamine VitB1] to shuttle 2-carbon fragment between sugar molecules & to convert [Fructose6phosphate] w/the help of TransAldolase
[Aldolase B Deficiency] MOD.
Hereditary Fructose intolerancE
- THIS CAN BE LIFE THREATENING*
- Surcose –> Fructose & Glucose*
[Fructokinase Deficiency] MOD
Fructose from diet is absorbed & secreted into urine due to impairment of Fructose —(Fructokinase)—> Fructose1P
*Detected via Positive Copper Reduction Test*
What is the function of [AcylCoA Dehydrogenase] and how is it related to fasting?
Catalyzes first step in B-oxidation of Fatty acids and ironically, the most commonly deficient.
Without it –> hypOglycemia with fasting
NAD+ is required to convert _____ into ____ during glycolysis. What occurs under ANaerobic conditions?
NAD+ converts [Glyceradehyde3Phosphate] –> [1-3 Bisphosphoglycerate] during glycolysis
ANAerobic conditions: NADH transfers electrons to pyruvate –> Lactate and More NAD+
[Acute Intermittent Porphyria] tx (2)
Glucose vs. Hemin (Both inhibit ALA synthase activity)
Identify
How does [Short non-coding RNA sequences] such as ___ and ___ work?
microRNA & [small interfering RNA] both induce posttx gene silencing by base-pairing with complementary sequences on target mRNA molecules
Where is [Hormone sensitive Lipase] found and what is its function
Adipose; Breaks down Stored TAG –> Fatty Acids & Glycerol during starvation. Needed for Hepatic Gluconeogenesis & ketone body formation
Galactose is converted to Galactitol by _____ and can cause ___ eye damage if in excess –> _____.
This ultimately occurs from a _____ deficiency which should convert Galactose —> ____. How does Lactose play a role in this?
Galactose is converted to Galactitol by Aldose Reductase and can cause Osmotic eye damage if in excess—> Cataracts. This ultimately is from Galactokinase deficiency which should convert Galactose –> Galactose1P.
Lactose is converted –> Galactose by [BGalactoSidase]
[RiboFlavin B2] is a precursor for ___ and ___. Which of these participates in the TCA cycle?
FMN and FAD.
FAD acts as electron acceptor for [Succinate Dehydrogenase Complex 2] in ETC and converts succinate –> Fumarate in TCA
Explain how the [Phospholipase C] 2nd messenger system causes Ca+ release and smooth m. contraction?
Why is [Total T3 levels] normal in early hypOthyroidism?
T3 is converted from T4 in peripheral tissues and so only T4 (made from thyroid) may be initially low
What are [P Bodies]
Cytoplasmic important molecules for mRNA translation and degradation
When is the RAS oncogene normally active?
ONLY when bound to GTP
Proteins destined for Lysosomes require ______ to ensure proper transit through ______
Proteins destined for Lysosomes require [phosphorylation of mannose residues] to ensure proper transit through Golgi
[Ehlers Danlos] MOD
Heritable Abnormal Collagen formation from [Procollagen Peptidase deficiency (impaired cleavage of N-terminal propeptides)] –>abnormal collagen
____ is the most common NON-nuclear DNA in Eukaryotic cells. It codes for what 3 major things?
Mitchondria DNA
- [Oxidative metabolic pathway] proteins
- rRNA - for mitochondrial proteins
- tRNA - for mitochondrial proteins
Which parameter of O2 does not change with Methemoglobinemia?
O2 Partial Pressure (free floating)
Dissolved O2 in plasma is unrelated to HgB function
Why is Dysphagia a problem in Demented Elderly?
It’s a RF for Aspiration PNA –> Requires Hospitlization
Hyperammonemia is common in cirrhotic pts, from inability to metabolize _____ . How does this affect CNS?
[Nitrogenous Waste]; Crosses BBB –> Excess Glutamine accumulation within astrocytes–> DEC Glutamine needed for Glutamate neuroexcitatory actions
What’s the most abundant amino acid in collagen? How does it play a role in Collagen shape?
Glycine; Triple helical conformation of collagen is from reptitive amino acid sequence within each alpha chain. Glycine occupies every 3rd position on that chain (Gly - X - Y)
How does 2,3 BPG facilitate O2 release
Forms ionic bonds with beta-subunits of DeOxygenated HgBA and facilitates O2 release –> peripheral tissue
How is 2,3 BPG related to Fetal HgB
When 2,3 BPG is mutated –> [HgB A] starts to resemble [HgB F] since its O2 affinity will be much HIGHER
Which enzyme partially compensates for [Fructokinase deficiency: fructosuria]
Hexokinase converts excess dietary fructose –> [fructose6Phosphate] but this isn’t sufficient
Which Dz are snRNPs attacked in
SLE (by Smith Ab)
Alkaptonuria MOD
Not having [Homogentisic acid Dioxygenase] blocks Tyrosine metabolism –> accumulation of homogentisic acid
Alkaptonuria Clinical Presentation (3)
- Black Urine when exposed to air
- Blue connective tissue (sclerae & ear)
- Arthropathy
Alkaptonuria Mode of Inheritance
auto recessive
Which hormones utilize [Protein Kinase A] GPCR second messenger? (3)
TSH
Glucagon
PTH
[Marfan Syndrome MOD].
Where is this protein found normally (3)
[Fibrillin1 defect (an extracellular scaffold for elastin)]
- Lens
- Periosteum
- Aortic Media –> Aortic Root Dilation –> Dissection
What does Polycistronic mean with Bacterial mRNA
1 mRNA codes for several proteins at same time
Regulated by single promoter/operator and regulatory elements
Why does Fructose have a more rapid rate of metabolism than Glucose?
Dietary fructose –(Liver phosphorylated)–> F1P –> rapidly metabolized because it bypasses PFK1
PFK1 = major rate-limiting enzyme in glycoslysis
[Niemann Pick] MOD
Sphingomyelinase Deficiency –> accumulation of Sphingomyelin
[Niemann Pick] Clinical Presentation (3)
- Cherry Red Macular Spot
- Neuro Regression
- Hepatosplenomegaly (differentiates from Tay-Sachs)
Tay-Sachs Clinical Presentation (2)
- Cherry Red Macular Spot
- Neuro Regression
Tay-Sachs MOD
[B-Hexosaminidase A Deficiency] –> GM2 accumulation in neurons
How is [Malonyl-CoA] significant in Fatty acid synthesis
[Malonyl-CoA] inhibits [mitochondrial carinitine acyltransferase] –> inhibits Beta-oxidation
Malonyl-CoA is formed from acetyl-CoA
Name the genetic predisposition to Gout
[PRPP synthetase activating mutations] –> INC Risk for Gout due to abnormal purine regulation
Neutrophils are indicated in Gout pathology
How does Insulin stimulate glycogen synthesis once it activates Tyrosine Kinase signaling
Tyrosine Kinase activates Protein Phosphatase –> Dephosphorylates Glycogen Synthase –> Glycogenesis
How do Kidneys excrete Acid in Chronic acidemic states
Tubular epithelium metabolize Glutamine –> GlutamATe, generating NH4+ –> excreted in urine while HCO3 is ReAbsorbed
What is Southwestern blotting used to detect (3)
DNA-binding proteins (transcription factors vs. nucleases vs. histones)
[Alpha Glucosidase Acid Maltase] deficiency presents _____ with lysosomal ___ accumulation. Clinical manifestations (3)?
early infancy with lysosomal glycogen(PAS+) accumulation;
“Big Heart, Big Tongue, No Muscle”
- Cardiomegaly
- Macroglossia
- Muscular hypOtonia
What is the rate-limiting enzyme in the [Pentose Phosphate Pathway] and what does it produce
[Glucose - 6 - Phosphate Dehydrogenase] = Major source of Cellular NADPH
If deficient, will resemble [Glutathione Reductase deficiency] = [Hemolytic anemia from oxidative stress]
NADPH function (2)
Reduces Glutathione (preventing oxidative damage) and [Biosynthesis of Cholesterol/Fatty Acids/Steroids]
[Glutathione Reductase deficiency] may cause similar pathology
How is Cortisol related to Epi and NorEpi
Cortisol INC conversion of [Epi and NorEpi] in adrenal Medulla by INC expression of [phenylethanolamine methyltransferase]
What is Glucokinase and what Dz develops from its mutation?
[Pancreatic beta cell: Glucose Sensor] that controls rate of glucose entry into TCA cycle; [Maturity onset Diabetes of the young]
[McArdle Glycogen Storage Dz 5] MOD
Myophosphorylase Deficiency–> DEC Muscle Glycogenolysis
[McArdle Glycogen Storage Dz 5] presentation (3)
Myoglobinuria with Exercise
Why does HgB-S cause worst sx than HgB-C
HgBS has a valine substituted for glutamic acid @ 6th position of B-globin chain –> Hydrophobic interactions between different HgBs–> RBC Sickling
Explain the biochemistry for why INC [Fructose 2,6 Bisphosphate] Aids in the treatment of DM
Lead (poisoning) directly inhibits __ and ____
Lead (poisoning) directly inhibits [ALA Dehydratase] and Ferrochelatase
Intracellular Receptors that contain [Zinc finger binding domains] interact with which hormones? (3)
- Steroids
- Thyroid Hormone
- ADEK Vitamins
[Cori Debranching Glycogen Storage Dz 3] presentation (3)
- Short stature
- hypOglycemia
- Muscle weakness & hypOtonia
[Cori Debranching Glycogen Storage Dz 3] MOD
Debranching enzyme deficiency –> accumulation of glycogen with abnormal short outer chains (inability to degrade at alpha1-6 branch points)
Base excision repair corrects __base DNA. Describe the process starting with removing defective base (4)
Single;
- Glycosylases remove defective base
- Sugar-phosphate site is cleaved and removed by endonuclease & lyase
- DNA Pol replaces missing nucleotide
- Ligase seals remaining nick
PKU-Phenylketonuria Clinical Manifestation (4)
- Musty Odor
- Seizures (look for upward eye deviation)
- Eczema
- Retard
Orotic Aciduria MOD
Defective [5-UMP synthase]–> INC Urinary Orotic Acid –> DEC pyrimidine synthesis. Improved with Uridine supplement
What are Amatoxins and what do they inhibit
Toxin from Poisonous Mushrooms that inhibit [RNA Pol 2] –> NO mRNA synthesis
Which enzyme is impaired in Galactosemia and what do you expect to see in the urine?
GALT; [Reducing Substance Unmetabolized Sugar]
[Ehlers Danlos] Clinical Presentation (3)
Hypermobile Joints
Hyperelastic Skin
Easy Bruising & Hemarhtrosis
Glycerol, made from ____ in Fat can be used by ____ in the ____ to make Glucose
Glycerol, made from Triglycerides in Fat, can be used by Glycerol Kinase in the Liver& Kidney to make Glucose
This is often the case in DKA pts
Ab to Citrullinated proteins are highly associated with what Dz
Rheumatoid Arthritis
[Beta Glucuronidase] is implicated in what condition
Pigment Gallstones
It’s released from injured liver cells and bacteria bilirubin glucuronides –> unconjugated bilirubin
What is the recognition sequence for tRNA at its __ end
3 end recognition sequence = CCA
Homocystinuria is most commonly caused by what
Defect in Cystathionine Synthase –> inability to convert Homocysteine to Cysteine. The Homocysteine then accumulates –> Elevated Methionine
Homocysteine is Thrombotic!
Carinitine Deficiency MOD
Defective Fatty acid transport from cytoplasm into mitochondria –> prevents Beta-oxidation during fasting (No Acetoacetate)
All 3 [Prokaryotic DNA Pol] have the abiliy to do what?
ALL can remove mismatched nucleotides via [3–>5 exonuclease activity]
Only DNA Pol 1 has [5–>3 exonuclease activity]
Which intracellular pathway does GH use
JAK-STAT
Cytokines also use this pathway
____ converts glucose –>Sorbitol, which is then —> Fructose by _____. Where is this pathway most common? (2)
Aldose Reductase converts glucose –>Sorbitol, which is then –> Fructose by Sorbitol Dehydrogenase.
Lens & [Seminal Vesicles]
HgB molecules are structurally similar to ____. What does this mean?
myoglobin; if separated into alpha & beta monomers, the O2 disassociation curve would resembles myoglobins
[Mccune Albright] MOD
G Protein activating mutation
What is Heteroplasmy
Presence of both normal and mutated
mtDNA –> in variable expression in
mitochondrial dz
How does Carnitine deficiency affect the body?
Carnitine deficiency impairs fatty acid transport from cytplasm –>mitochondria –> Inhibits B-oxidation (formation of Acetoacetate) –> [Myocyte injury from lack of TCA ATP] + [DEC Hepatic ketone production]
Carnitine is a [Mitochondrial acyltransferase]
Which compound inhibits Carnitine
Malonyl-CoA
Arginase is a ____ cycle enzyme that makes __(2)___ from arginine. What’s clinical manifestation of Arginase deficiency? (2)
Arginase is an Urea cycle enzyme that makes [Urea & Ornithine] from arginine.
Deficiency = Progressive Spastic Diplegia + growth delay
[Biotin B7] is a cofactor for what type of enzymes? (3)
Any CARBOXYLATION enzymes!
- Pyruvate –> Oxaloacetate
- AcetylCoA —> MalonylCoA
- PropionylCoA –> MethylMalonylCoA
Function of Primase
RNA polymerase that incorporates short RNA primers into replicating DNA
Where are [Very Long chain fatty acids] & [Fatty acids with branch points at odd # carbons] oxidized?
Peroxisomes
Function of Lactate Dehydrogenase
Pyruvate –> Lactate ; ANEROBIC
_____ is the AA that transfers nitrogen to Liver for disposal. How is Nitrogen eliminated? (2)
Alanine;
- Amino groups are transfered to a-ketoglutarate –> Glutamate –> [Forms Urea in Liver] –> Urinated out
- Free Amonia also urinated out
Alanine must transfer Amino group before conversion to Glucose
In which parts of the TCA cycle do you get ___(x)___ and how many ATP do they give
A: NADH
B: GTP
C: FADH2
Can I Keep Selling Sex For Money, Officer?
A: NADH = 2.5 ATP each = (I-Keep) (Keep-Selling) (Money-Officer)
B: GTP = 1 ATP = (Selling - Sex) - used in Gluconeogenesis by PEP Carboxykinase to convert Oxaloacetate–>PEP
C: FADH2 = 1.5 ATP each = (Sex - For)
