Human Metabolism – Protein Structure, Function & Metabolic Regulation

A comprehensive set of Q&A flashcards covering protein structure, amino-acid chemistry, enzyme kinetics, metabolic regulation, nutrient catabolism and anabolism, lipid/cholesterol biology, and clinical correlations relevant to human metabolism.

What defines a polypeptide?

A linear hetero-polymer of amino acids linked by peptide bonds formed through dehydration synthesis.

How does a protein differ from a single polypeptide?

A protein may consist of one or more polypeptide chains folded into a specific 3-D structure and often associated with prosthetic groups.

What is a protein subunit?

An individual polypeptide chain that associates (covalently or non-covalently) with other chains to form a multi-subunit protein complex.

Give an example of a prosthetic group and its role.

Heme in hemoglobin; it binds O₂ and is essential for oxygen transport.

Name three key factors that determine a protein’s function.

Its amino-acid sequence (chemical structure), three-dimensional conformation, and molecular recognition properties.

What is the primary transport function of hemoglobin?

Carrying O₂ from lungs to tissues and returning CO₂ to the lungs.

Which proteins provide major structural support in connective tissue?

Collagen and elastin.

How many standard amino acids are incorporated into proteins?

Twenty.

Which two functional groups are found on every α-amino acid?

A primary amine (–NH₃⁺) and a carboxyl group (–COO⁻).

Why is glycine achiral?

Its α-carbon carries two identical hydrogen atoms, so it lacks four different substituents.

What are enantiomers and which form predominates in proteins?

Non-superimposable mirror images (L and D); almost all natural proteins use the L-form.

How do dextrorotatory (D) and levorotatory (L) enantiomers differ?

D rotates plane-polarized light clockwise; L rotates it counter-clockwise.

Name the two acidic side-chain amino acids.

Aspartic acid (Asp) and glutamic acid (Glu).

List three basic side-chain amino acids.

Lysine (Lys), arginine (Arg), histidine (His).

What is meant by ‘hydrophobic effect’ in protein folding?

Non-polar side chains bury inside the protein away from water, driving folding and stability.

Define a peptide bond.

An amide linkage between the α-carboxyl of one amino acid and the α-amine of the next.

What distinguishes the N-terminus from the C-terminus of a peptide?

N-terminus has a free amino group; C-terminus has a free carboxyl group.

Why is the peptide bond rigid?

Resonance gives it partial double-bond character, restricting rotation.

Name the four hierarchical levels of protein structure.

Primary, secondary, tertiary, and quaternary structures.

What pattern of hydrogen bonding forms an α-helix?

Backbone C=O of residue i hydrogen-bonds to N–H of residue i+4.

List two types of bonds stabilizing tertiary structure.

Hydrogen/ionic bonds and covalent disulfide bonds.

Give an example of a protein with quaternary structure.

Hemoglobin, composed of four subunits.

What four general folding classes describe protein architecture?

All-α, all-β, α+β (separate), and α/β (alternating).

Which classic fold is seen in myoglobin?

The globin fold (all-α).

What is a TIM barrel?

A common α/β fold of eight parallel β-strands surrounded by eight α-helices (e.g., triose phosphate isomerase).

What are essential amino acids?

Amino acids humans cannot synthesize and must obtain from the diet.

Give three examples of essential amino acids.

Leucine, lysine, and tryptophan.

Which enzyme initiates protein digestion in the stomach?

Pepsin.

What is deamination and why is it important?

Removal of an amino group from an amino acid to form a carbon skeleton for energy metabolism.

Define glucogenic amino acids.

Amino acids whose carbon skeletons can be converted into glucose via gluconeogenesis.

Define ketogenic amino acids.

Amino acids degraded to acetyl-CoA or acetoacetate, precursors of ketone bodies or lipids.

What is the purpose of the urea cycle?

To convert toxic ammonia into urea for safe excretion.

Name a disorder caused by urea-cycle enzyme deficiency.

Hyperammonemia (e.g., ornithine transcarbamylase deficiency).

What does the ubiquitin–proteasome system do?

Tags damaged or unneeded proteins with ubiquitin and degrades them in the proteasome.

What is a signal peptide?

An N-terminal 13–35-residue sequence that directs ribosome–nascent chains to the rough ER.

Where are secretory proteins synthesized?

On ribosomes bound to the rough endoplasmic reticulum (RER).

Which carbohydrate tag targets proteins to lysosomes?

Mannose-6-phosphate.

What C-terminal retention signal keeps soluble ER proteins resident?

KDEL (Lys-Asp-Glu-Leu).

Define metabolism.

The sum of all chemical reactions sustaining life in cells.

Differentiate catabolism and anabolism.

Catabolism breaks molecules down to release energy; anabolism builds complex molecules using energy.

What are amphibolic pathways?

Pathways that function in both catabolism and anabolism (e.g., TCA cycle).

What does Vmax represent in enzyme kinetics?

The maximal reaction rate when the enzyme is saturated with substrate.

What is Km?

Substrate concentration at which reaction velocity is half of Vmax; indicates substrate affinity.

How does a competitive inhibitor affect Km and Vmax?

Increases Km (lower affinity) but leaves Vmax unchanged.

What is the effect of an uncompetitive inhibitor on Vmax?

It decreases Vmax (and proportionally lowers Km).

What cellular role does AMPK serve?

It senses low energy (high AMP) and activates catabolic pathways to generate ATP.

How does high ATP act on phosphofructokinase (PFK)?

ATP allosterically inhibits PFK, slowing glycolysis when energy is abundant.

Define feedback inhibition.

Down-regulation of a pathway by its end product binding to an upstream enzyme.

What is an isozyme?

Different molecular forms of an enzyme that catalyze the same reaction but differ in kinetics/regulation.

Contrast hexokinase and glucokinase.

Hexokinase (muscle) has low Km and is inhibited by G-6-P; glucokinase (liver) has high Km and is not inhibited by product.

What BMI is classified as overweight?

BMI ≥ 25 kg m⁻².

State one serious complication of chronic hyperglycaemia.

Protein glycation leading to vascular damage (e.g., diabetic retinopathy).

Name three glucose polymers and their biological roles.

Starch (plant energy), glycogen (animal energy), cellulose (plant structural fiber).

What type of glycosidic bond links glucose units in cellulose?

β(1→4) linkages.

What is a reducing sugar?

A carbohydrate with a free anomeric carbon capable of reducing mild oxidizing agents.

Define lipotoxicity.

Damage to tissues caused by accumulation of excess lipids, contributing to insulin resistance and organ dysfunction.

Identify the rigid four-ring lipid that modulates membrane fluidity.

Cholesterol.

What are lipoproteins?

Particles of lipid and protein that transport hydrophobic lipids in blood.

Which lipoprotein is called “good cholesterol” and why?

HDL, because it transports cholesterol from tissues back to the liver for excretion.

What does VLDL mainly transport?

Endogenous (hepatic) triacylglycerol to peripheral tissues.

Summarize β-oxidation.

Mitochondrial cyclic cleavage of fatty acyl-CoA two carbons at a time to yield acetyl-CoA, NADH, and FADH₂.

Which shuttle transports long-chain fatty acyl groups into mitochondria?

Carnitine palmitoyltransferase (CPT) system.

Approximate total ATP yield from complete oxidation of one glucose molecule?

About 30–34 ATP (≈33).

Roughly how many ATP are generated from one palmitate (C₁₆) molecule?

≈113 ATP.

What is proton motive force (PMF)?

Electrochemical gradient of protons across the inner mitochondrial membrane that drives ATP synthesis.

What is the function of UCP1 in brown fat?

Creates proton leak to generate heat (non-shivering thermogenesis) instead of ATP.

Name a historical chemical uncoupler once used for weight loss.

2,4-Dinitrophenol (DNP).

What is the Cori cycle?

Conversion of muscle lactate to glucose in the liver, then return of glucose to muscle.

Which enzyme is deficient in Von Gierke disease?

Glucose-6-phosphatase.

Which hormone stimulates glycogenesis after a high-carbohydrate meal?

Insulin.

Main metabolic action of glucagon?

Stimulates glycogenolysis and gluconeogenesis to raise blood glucose during fasting.

Which enzyme in cholesterol synthesis is inhibited by statins?

HMG-CoA reductase.

Name the three physiological ketone bodies.

Acetoacetate, β-hydroxybutyrate, and acetone.

Which antidiabetic drug lowers hepatic gluconeogenesis?

Metformin (a biguanide).

What pathway converts excess glucose into fatty acids?

Lipogenesis (fatty-acid synthesis) in liver/adipose tissue.

Which metabolite is the committed precursor for fatty-acid synthesis?

Malonyl-CoA.

Define hypercholesterolemia.

Elevated LDL-cholesterol levels in blood, increasing atherosclerosis risk.

What metabolic imbalance triggers diabetic ketoacidosis?

Excessive ketone production when insulin is absent or ineffective.

What is substrate-level phosphorylation?

Direct formation of ATP (or GTP) by transfer of a phosphate group from a high-energy substrate, independent of the ETC.

What does the P/O ratio express?

ATP molecules synthesized per oxygen atom reduced during oxidative phosphorylation.

Define proton leak in mitochondria.

Return of protons to the matrix without ATP synthesis, lowering coupling efficiency.

What is the primary role of brown adipose tissue in adults?

Heat generation through UCP1-mediated uncoupling, contributing to thermoregulation and energy expenditure.

Why is the Cori cycle important during intense exercise?

It clears lactate from muscles and supplies glucose back, preventing acidosis and sustaining ATP production.

Which enzyme illustrates product inhibition by its own product glucose-6-phosphate?

Hexokinase.

How do sulfonylurea drugs stimulate insulin release?

They close KATP channels in pancreatic β cells, depolarizing membranes and triggering insulin exocytosis.

What is the purpose of metabolic control analysis (MCA)?

Quantifies how individual enzymes control overall flux and metabolite levels in a pathway.

What is the role of the branching enzyme in glycogen synthesis?

Introduces α(1→6) branches, increasing solubility and sites for rapid glucose release.

Name two mitochondrial shuttles that move cytosolic NADH electrons inside.

Malate–aspartate shuttle and glycerol-3-phosphate shuttle.