hemoglobin, myoglobin, and metabolism !

What is myoglobin's main function?

Oxygen storage in muscle.

What is hemoglobins main function?

Oxygen transport in blood.

myoglobin's structure? how does it impact the curve shape? cooperativity?

A monomer containing one heme group and one oxygen-binding site.

hyperbolic curve and no cooperativity bc only one O binding site

hemoglobin’s structure? how does it impact the curve shape? cooperativity?

An α₂β₂ tetramer containing four heme groups.

S curve bc has 4 O bonding sites, positive cooperativity

heme

A porphyrin ring containing Fe²⁺ that reversibly binds oxygen.

Connect the heme iron, His F8 and salt bridges to the T→R transition O2 BINDING

O₂ binds Fe²⁺ → Fe²⁺ pulls His F8 → F helix shifts → T-state salt bridges break → R state favored → remaining O₂ molecules bind more easily → sigmoidal curve and Hill coefficient > 1.

T state of hemoglobin?

Tense, lower oxygen affinity.

What is the R state of hemoglobin?

Relaxed, higher oxygen affinity.

What stabilizes hemoglobin's T state?

Salt bridges, hydrogen bonds, and interactions with allosteric effectors such as 2,3-BPG.

Hill coefficient?

A measure of cooperativity in ligand binding.

Hill coefficient of 1, >1, <1?

1= No cooperativity.

>1 positive cooperativity

<1. Negative

What is the Bohr effect?

Decreasing pH decreases hemoglobin's oxygen affinity, promoting oxygen unloading.

What happens to oxygen affinity when pH decreases?

Affinity decreases; the binding curve shifts right.

What happens to oxygen affinity when pH increases?

Affinity increases; the binding curve shifts left.

How does increased CO₂ affect hemoglobin?

It lowers oxygen affinity through H⁺ generation and direct carbaminohemoglobin formation.

What happens to hemoglobin in metabolically active tissues?

Increased CO₂ and H⁺ favor T state and promote oxygen unloading.

What does a right shift in the O₂-binding curve mean?

Lower oxygen affinity and easier oxygen unloading.

What does a left shift mean?

Higher oxygen affinity and tighter oxygen binding.

What is 2,3-BPG?

A negatively charged allosteric effector that decreases hemoglobin oxygen affinity.

binds in The positively charged central cavity between hemoglobin's β subunits.

What is adult hemoglobin HbA composed of?

Two α chains and two β chains (α₂β₂).

What is fetal hemoglobin HbF composed of?

Two α chains and two γ chains (α₂γ₂).

Why does fetal hemoglobin have higher oxygen affinity?

Its γ chains bind 2,3-BPG less strongly, reducing T-state stabilization.

γ-chain Ser143 replaces β-chain His143.

Why is fetal hemoglobin's higher affinity important?

It facilitates oxygen transfer from maternal to fetal blood across the placenta.

What mutation causes sickle-cell hemoglobin (HbS)? why?

Glutamate at β-chain position 6 is replaced by valine (Glu6→Val).

Glutamate is negatively charged and hydrophilic; valine is nonpolar and hydrophobic.

Why does sickling occur more readily at low oxygen?

The deoxygenated conformation permits the intermolecular interactions that drive HbS polymerization.

Why does HbS polymerize?

Val6 creates a hydrophobic patch that interacts with a pocket on neighboring deoxygenated HbS molecules.

It causes red blood cell destruction and blood vessel obstruction, leading to anemia and tissue injury.

What is metabolism?

The complete set of chemical reactions occurring in living organisms.

What is catabolism?

Breakdown of complex molecules into simpler molecules, generally releasing energy.

What is anabolism?

Synthesis of complex molecules from simpler precursors, requiring energy.

How do catabolism and anabolism differ energetically?

Catabolism generally releases energy; anabolism generally consumes energy.

What are the three stages of catabolism?

Macromolecule breakdown, formation of common intermediates, and oxidation with ATP production.

What happens during stage 1 of catabolism?

Macromolecule breakdown-Proteins, carbohydrates, and lipids are broken into smaller building blocks.

What happens during stage 2 of catabolism?

formation of common intermediates- Building blocks are converted into common intermediates such as acetyl-CoA.

What happens during stage 3 of catabolism?

oxidation with ATP production- Intermediates are oxidized and their energy is captured through electron carriers and ATP production.

What is glucose homeostasis?

Maintenance of blood glucose within a healthy physiological range.

What is insulin?

A hormone released by pancreatic β-cells that promotes nutrient uptake and storage.

released when blood glucose rises

What is glucagon?

A hormone released by pancreatic α-cells that promotes glucose production and fuel mobilization.

released when blood glucose falls

What does insulin stimulate?

Glycogenesis, glycolysis in relevant tissues, lipogenesis, and protein synthesis.

What does glucagon stimulate?

Liver glycogenolysis, gluconeogenesis, and fasting-related fuel mobilization.

insulin/glucagon ratio

compares how much insulin signaling there is relative to glucagon signaling.

HIGH insulin/glucagon ratio

glycogen synthesis.

FED STATE and STORAGE.

LOW insulin/glucagon ratio

Promotes glycogen breakdown and glucose production by the liver.

FASTING and MOBILIZATION.

GLUT transporters

low facilitated diffusion of glucose down its concentration gradient.

What does insulin do to GLUT4?

Promotes its movement to the plasma membrane, increasing glucose uptake.

glucagon signaling pathway

Glucagon binds to a G-protein-coupled receptor (GPCR).

That activates a G protein, which stimulates adenylyl cyclase.

Adenylyl cyclase converts ATP into cAMP.

cAMP activates protein kinase A (PKA).

insulin signaling pathways

Insulin binds receptor → GLUT4 moves to membrane → more glucose enters muscle/fat cells → blood glucose decreases.

Why is the insulin/glucagon ratio more important than either hormone alone?

even if insulin is present, if glucagon's influence is relatively greater, the body can still be in a fasting metabolic state.

Glucose cannot easily pass through the hydrophobic lipid bilayer on its own, why? what does it do instead

it is polar

Instead, it uses GLUT transporters, which allow facilitated diffusion of glucose down its concentration gradient.

GLUT1

Red blood cells, blood-brain barrier

Basal glucose uptake

GLUT 2

Liver, intestine, kidney, pancreatic β cells (especially in rodents)

High-capacity, bidirectional transport; glucose sensing in some species

GLUT3

Neurons

High affinity for glucose

GLUT4 !!!!

Skeletal muscle, cardiac muscle, adipose tissue

Insulin-responsive glucose uptake

Why doesn't the liver need insulin to take up glucose?

The liver uses GLUT2, which is not dependent on insulin for membrane insertion.

So glucose can enter and leave liver cells through GLUT2 according to its concentration gradient.

However, insulin still regulates what the liver does with glucose once it enters.

Reciprocal regulation of opposing pathways

when one metabolic pathway is activated, the opposing pathway is inhibited.

Because running both pathways at high rates simultaneously would waste energy.

(Glycogenesis (make glycogen)) and (Glycogenolysis (break down glycogen))

give an example of reciprocal regulation

When glucagon binds its receptor in the liver:

Glucagon → cAMP → PKA

PKA activates phosphorylase kinase, which activates glycogen phosphorylase (glycogen breakdown)

PKA phosphorylates and inhibits glycogen synthase

The liver also regulates what pathways reciprocally?

Glycolysis (break down glucose)

Gluconeogenesis (make glucose)

What is standard reduction potential (E°′)

ells you how strongly a molecule tends to accept electrons under biochemical standard conditions

More negative E°′

more willing to give away electrons (when in the reduced form).

More positive E°′

more willing to accept electrons (when in the oxidized form).

direction of electron flow

from most neg —> most positive

positive ΔE° (spontaneous or not?)

spontaneous

negative ΔE° (spontaneous or not?)

non spontaneous

water-soluble B vitamins

B1- Thiamine, B2- RIboflavin, B3-Niacin, B5- Panothenic acid, B6- Pyridoxine family, B7- biotin, B9-Folate, B12- Cobalamin

B1 - Thiamine. the coenzyme it becomes, and the type of reaction it supports.

TPP (thiamine pyrophosphate)

Decarboxylation of α-keto acids; two-carbon transfers

B2 — Riboflavin. the coenzyme it becomes, and the type of reaction it supports.

FAD, FMN

Oxidation–reduction (electron transfer)

B3 — Niacin. the coenzyme it becomes, and the type of reaction it supports.

NAD⁺, NADP⁺

Oxidation–reduction (electron transfer)

B5 — Pantothenic acid. the coenzyme it becomes, and the type of reaction it supports.

Coenzyme A (CoA)

Acyl-group transfer

B6 — Pyridoxine family. the coenzyme it becomes, and the type of reaction it supports.

PLP (pyridoxal phosphate)

Amino acid reactions, especially transamination and decarboxylation

B7 — Biotin. the coenzyme it becomes, and the type of reaction it supports.

Biotin (enzyme-bound)

Carboxylation (adding CO₂)

B9 — Folate. the coenzyme it becomes, and the type of reaction it supports.

THF (tetrahydrofolate)

One-carbon group transfer

B12 — Cobalamin. the coenzyme it becomes, and the type of reaction it supports.

Methylcobalamin, adenosylcobalamin

Methyl transfer and molecular rearrangements

ATP

drives endergonic reactions (energy-requiring cellular activities are powered by ATP hydrolysis)

NADH and FADH₂

electron carriers for catabolism (delivering e- to the ETC – with O₂ being the final e- acceptor, becoming reduced to H₂O)

NADPH

electron carrier from catabolic reactions to anabolic reactions (provides reducing power for biosynthesis: fatty acid synthesis, cholesterol synthesis, amino acid synthesis, nucleotide synthesis)

Glycolysis

Breaks down glucose into pyruvate to make ATP.

Gluconeogenesis

Makes NEW glucose from non-carbohydrate sources.

Glycogenesis

Converts glucose into glycogen for STORAGE.

Glycogenolysis

Breaks down stored glycogen to release glucose units.