Proteins & Amino Acids Comprehensive Practice

A collection of practice flashcards covering general amino acid concepts, levels of protein structure, specific protein pathologies, and the physiological regulation of hemoglobin and myoglobin based on the lecture transcripts.

What is the origin of the word "protein" and its general importance in the body?

Proteins are derived from "proteos" (meaning "of primary importance") and are the most abundant organic molecules in the body, versatile in their interactions with other biomolecules.

Which amino acid is the only one that is achiral, and why?

Glycine is the only achiral amino acid because its side chain (R group) is a simple hydrogen atom, meaning it does not have four different groups attached to the alpha carbon.

Contrast the biological occurrence of $L$-Configuration and $D$-Configuration amino acids.

Levorotatory ($L$-Configuration) amino acids are found in almost all human proteins and biological reactions, while Dextrorotatory ($D$-Configuration) isomers are found in bacterial cell walls and certain antibiotics.

What is the "21st amino acid," and what specific substitution does it contain?

The 21st amino acid is Selenocysteine, where selenium replaces the sulfur atom found in cysteine; it is found in redox-involved enzymes like peroxidases.

How does the toxin tetanospasmin from $Clostridium\,tetani$ cause spastic paralysis?

The toxin cleaves SNARE proteins, which prevents the release of inhibitory neurotransmitters Glycine and GABA from Renshaw cells in the spinal cord.

Explain the role of Alanine in the Glucose-Alanine Cycle.

Alanine acts as the major carrier of ammonia and pyruvate carbon skeletons from skeletal muscles to the liver.

Which branched-chain amino acid (BCAA) is exclusively ketogenic?

Leucine is exclusively ketogenic.

What biochemical deficiency causes Maple Syrup Urine Disease (MSUD), and what are its symptoms?

MSUD is caused by a deficiency in Branched-chain $\alpha$-keto acid dehydrogenase (BCKD), leading to BCAA accumulation, sweet-smelling urine, fluctuating muscle tone, and seizures/cerebral edema due to leucine buildup.

Why is Proline technically referred to as an "imino acid" rather than a true amino acid?

Proline contains a secondary amine within its cyclic side chain structure rather than a primary amino group ($-NH_2$).

What is the primary methyl-group donor derived from Methionine?

$S$-Adenosylmethionine (SAM) is the primary methyl-group donor and carrier for biomolecule methylation.

Elevated levels of which amino acid metabolite are linked to cardiovascular disease, atherosclerosis, and thrombosis?

Elevated Homocysteine levels.

State the metabolic outcome of the deficiency in phenylalanine hydroxylase.

It causes Phenylketonuria (PKU), resulting in phenylalanine accumulation and a characteristic musty or mousy body odor.

What are the three major derivatives of Tryptophan?

Serotonin (5-hydroxytryptamine), Melatonin, and Niacin ($Vitamin\,B_3$).

Identify the primary cellular locations for O-linked and N-linked glycosylation.

O-linked glycosylation occurs in the Golgi apparatus, while N-linked glycosylation occurs in the Rough Endoplasmic Reticulum (RER).

What covalent bond, formed by the oxidation of two cysteine residues, stabilizes protein structure?

A Disulfide Bond, which turns two Cysteine residues into a Cystine molecule.

Distinguish the functions of Glutamate and GABA as neurotransmitters.

Glutamate is the major excitatory neurotransmitter of the CNS, whereas GABA (Gamma-Aminobutyric Acid) is the major inhibitory neurotransmitter of the brain.

Which basic amino acid acts as an effective $pH$ buffer in proteins like hemoglobin, and why?

Histidine, because its side chain $pKa$ is near physiologic $pH$.

List the two amino acids that are exclusively ketogenic.

Leucine and Lysine (the two "L" amino acids).

Which two amino acids do not undergo a transamination step during catabolism?

Lysine and Threonine.

Why is a peptide bond considered to have "partial double-bond character"?

Due to resonance between the carbonyl carbon and the amide nitrogen, which makes the bond rigid, planar, and resistant to rotation.

What is the "Isoelectric Point" ($pI$) of an amino acid?

The specific $pH$ at which the amino acid has no net electrical charge and exists predominantly as a zwitterion.

How does lowering the $pH$ affect an amino acid's charge and migration during electrophoresis?

In an acidic (low $pH$) environment, amino acids become protonated, gaining a net positive charge and migrating toward the cathode.

In conjugated proteins, what is the non-protein component called?

The prosthetic group (e.g., heme, lipid, or carbohydrate).

What is the fundamental difference between protein denaturation and protein misfolding?

Denaturation is the unfolding of secondary, tertiary, and quaternary structures without breaking peptide bonds (primary structure intact); misfolding involves proteins adopting incorrect three-dimensional conformations (like amyloid fibrils) that can lead to disease.

Describe the specific molecular mutation responsible for Sickle Cell Anemia.

A point mutation in the $\beta$-globin chain where polar Glutamate is replaced by nonpolar Valine at the 6th position, creating a hydrophobic patch on the hemoglobin surface.

What determines the secondary structure of a protein?

Regular local folding of the polypeptide backbone stabilized by hydrogen bonds between carbonyl oxygens and amide hydrogens.

Which two amino acids are known as "helix breakers" that disrupt $\alpha$-helices?

Proline (due to its rigid cyclic structure) and Glycine (due to its high flexibility).

Contrast the orientation of hydrogen bonds in $\alpha$-helices versus $\beta$-sheets.

In $\alpha$-helices, hydrogen bonds run parallel to the helical axis; in $\beta$-sheets, they are oriented perpendicular to the polypeptide backbone.

What are the four primary forces that stabilize the tertiary structure of a protein?

Hydrophobic interactions (the major driving force), hydrogen bonds, ionic bonds (salt bridges), and disulfide bonds.

What is the function of Hsp70 and chaperonins in the cell?

Hsp70 binds hydrophobic regions to prevent aggregation of unfolded proteins; chaperonins provide an isolated chamber/environment for proteins to fold correctly.

In Alzheimer's disease, what is the composition of amyloid plaques and neurofibrillary tangles?

Amyloid plaques are composed of extracellular amyloid beta ($A\beta$) peptides ($\beta$-pleated sheets); neurofibrillary tangles are composed of intracellular hyperphosphorylated tau protein.

What conformational change occurs in prion diseases like Creutzfeldt-Jakob disease?

Normal cellular prion protein ($PrP^C$), which is rich in $\alpha$-helices, undergoes a change into the pathogenic form ($PrP^{Sc}$), which is rich in $\beta$-sheets and resistant to proteolysis.

Differentiate between myoglobin and hemoglobin regarding oxygen storage and transport.

Myoglobin is a monomer that stores oxygen in muscle; Hemoglobin is a tetramer that transports oxygen from the lungs to tissues and displays cooperative binding.

What does a "sigmoidal" oxygen dissociation curve indicate for Hemoglobin?

It indicates cooperative binding, where the binding of one oxygen molecule increases the affinity of the remaining heme groups for oxygen.

Briefly describe the T (Tense) and R (Relaxed) states of hemoglobin.

The T (Tense) state is the deoxy form with low oxygen affinity stabilized by ionic bonds; the R (Relaxed) state is the oxygenated form with high oxygen affinity and increased flexibility.

How does $2,3$-Bisphosphoglycerate ($2,3-BPG$) regulate hemoglobin oxygen affinity?

$2,3-BPG$ binds to deoxyhemoglobin, stabilizing the T state and decreasing oxygen affinity to facilitate oxygen unloading in tissues.

Why does Fetal Hemoglobin ($HbF$) have a higher oxygen affinity than Adult Hemoglobin ($HbA$)?

$HbF$ consists of two alpha and two gamma chains; its gamma chains do not bind $2,3-BPG$ as strongly as the beta chains of $HbA$, leading to higher affinity.

Explain the Bohr Effect.

A decrease in $pH$ (increased acidity) or an increase in $pCO_2$ reduces hemoglobin's affinity for oxygen, promoting oxygen unloading in metabolically active tissues.

How does carbon monoxide ($CO$) poisoning affect hemoglobin function?

Carbon monoxide binds with 220 times greater affinity than oxygen, shifting the dissociation curve to the left and trapping oxygen on the hemoglobin molecule, preventing delivery to tissues.

Distinguish the functions of the Fab and Fc regions of an immunoglobulin.

The Fab region contains the antigen-binding site and variable regions; the Fc region contains only heavy chains/constant regions and determines the isotype while binding to complement and macrophages.

Describe the function of the enzyme Protein Disulfide Isomerase (PDI).

PDI catalyzes the formation, breaking, and rearrangement of disulfide bonds to help a protein reach its correct native conformation during folding.

What is the role of Vitamin C in collagen synthesis?

Vitamin C is a required cofactor for prolyl hydroxylase and lysyl hydroxylase, which hydroxylate proline and lysine residues to stabilize the collagen triple helix.

What is the clinical significance of Hemoglobin A1c (HbA1c)?

Its levels reflect the nonenzymatic glycation of N-terminal valines on beta-globin chains over the 120-day lifespan of red blood cells, serving as a marker for long-term plasma glucose exposure.