• KM is unchanged - the enzyme's affinity for substrate is not affected
• Vmax is reduced - the inhibitor reduces the total number of functional enzyme molecules, so even at saturating substrate concentrations, maximum velocity cannot reach the uninhibited Vmax

• B2 (Riboflavin) and B1 (Thiamine) are water-soluble B vitamins - they are not stored and excess is excreted in urine.
• C (Ascorbic acid) is water-soluble - not stored in significant amounts.
• H (Biotin, vitamin B7) is water-soluble - not stored.
• P (Rutin/Bioflavonoids) is water-soluble - not stored.

• Elfin facies
• Supravalvular aortic stenosis
• Mild-to-moderate intellectual disability
• Hypercalcemia (due to increased sensitivity to vitamin D)
• Friendly/overly social personality ("cocktail party personality")

• Prolyl hydroxylase - hydroxylates proline residues → hydroxyproline
• Lysyl hydroxylase - hydroxylates lysine residues → hydroxylysine

• b) Blood clotting - This is the role of Vitamin K, not C
• c) Aid iron absorption - Vitamin C does enhance non-heme iron absorption (by reducing Fe³⁺ to Fe²⁺), but this is a secondary/indirect function, not the primary one
• d) Bone mineralization - This is primarily the role of Vitamin D and K, not C (though collagen synthesis by Vit C does support bone matrix)

• Occurs in mitochondria
• 2 ATP consumed (one per pyruvate × 2)
• Biotin is the cofactor

• 2 GTP consumed (one per OAA × 2)
• CO₂ is released

• 2 ATP consumed (one per molecule × 2)
• This step requires ATP to form 1,3-BPG from 3-PG

• 2 NADH consumed (one per molecule × 2)
• Reduces 1,3-BPG back up the pathway

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH + 4 H₂O → Glucose + 4 ADP + 2 GDP + 2 NAD⁺ + 6 Pᵢ

• α-D-glucose: -OH at C-1 is axial (below the ring plane)
• β-D-glucose: -OH at C-1 is equatorial (above the ring plane)

Stereoisomers (broad)
├── Enantiomers (mirror images, all chiral centers differ)
└── Diastereomers
    ├── Epimers (differ at one carbon, not anomeric)
    └── Anomers (differ only at anomeric carbon = C-1)

• It occurs by acid-catalyzed dehydration of the carbon skeleton
• Does not require a free anomeric -OH
• Even glycosides (where the anomeric -OH is blocked) can form furfural
• It is a property of the ring structure/carbon chain, not the carbonyl reactivity

• In the liver: PKA phosphorylation activates the phosphatase domain and inhibits the kinase domain → less F-2,6-BP → favors gluconeogenesis (fasting state, glucagon signaling)
• In the heart: PKA phosphorylation activates the kinase domain → more F-2,6-BP → favors glycolysis

Glucagon → cAMP ↑ → PKA activated → PFK-2 phosphorylated → kinase domain inhibited + phosphatase domain activated → F-2,6-BP ↓ → PFK-1 inhibited → glycolysis ↓, gluconeogenesis ↑

High glucose (fed state):
F-6-P → F-2,6-BP  [PFK-2 kinase domain active]
F-2,6-BP → activates PFK-1 → glycolysis ↑

Fasting/Glucagon state:
PKA phosphorylates PFK-2 (liver) → phosphatase domain active
F-2,6-BP → F-6-P → PFK-1 less active → gluconeogenesis ↑

• b) Phosphohexose isomerase - freely reversible, not regulatory
• c) G3P dehydrogenase - important but not the rate-limiting step
• d) Enolase - inhibited by fluoride (used in lab) but not the rate-limiting enzyme physiologically

• Step 1 - Pyruvate Carboxylase (mitochondria):
  • Pyruvate + CO₂ + ATP → Oxaloacetate + ADP + Pi
  • Uses ATP only
• Step 2 - PEPCK (cytosol):
  • Oxaloacetate + GTP → Phosphoenolpyruvate + CO₂ + GDP
  • Uses GTP only

Pyruvate
   ↓  [Pyruvate Carboxylase] + ATP + CO₂  (MITOCHONDRIA)
Oxaloacetate
   ↓  shuttle as Malate/Aspartate
Oxaloacetate (CYTOSOL)
   ↓  [PEPCK] + GTP → CO₂ released
Phosphoenolpyruvate (PEP)

NADH → Complex I → CoQ ←── Complex II (FADH₂)
                    ↓
               Complex III (Cytochrome b → Cytochrome c₁)
                    ↓
               Cytochrome C (mobile carrier)
                    ↓
               Complex IV (Cytochrome a → a₃)
                    ↓
                   O₂ → H₂O

Acetyl-CoA → (Fatty Acid Synthase complex)
              requires NADPH at two steps:
              1. β-ketoacyl-ACP reductase
              2. Enoyl-ACP reductase
              
Each 2-carbon elongation requires 2 NADPH
Synthesis of palmitate (16C) requires 14 NADPH

• HMP shunt is most active in tissues with high lipid synthesis: liver, adipose tissue, adrenal cortex, mammary gland, RBCs
• In RBCs, NADPH is used to regenerate reduced glutathione (GSH) to protect against oxidative damage

"Lactating mammary glands, Adrenal cortex, Liver, Testes, Erythrocytes" = all sites of active NADPH use for lipid/steroid synthesis or antioxidant defense.

• Insulin can no longer inhibit glucagon release
• Alpha cells continue secreting glucagon even in the presence of high insulin levels
• Result: paradoxical hyperglucagonemia despite hyperinsulinemia

Insulin resistance (peripheral tissues)
         ↓
Compensatory hyperinsulinemia (beta cells work harder)
         ↓
Alpha cells also resistant to insulin
         ↓
Glucagon suppression fails → Hyperglucagonemia
         ↓
Glucagon stimulates hepatic glucose output
         ↓
Worsens hyperglycemia

• Hyperglucagonemia in T2DM contributes significantly to fasting hyperglycemia by driving hepatic glucose production (glycogenolysis + gluconeogenesis)
• This is why GLP-1 receptor agonists (e.g., semaglutide, liraglutide) are effective in T2DM - they suppress inappropriate glucagon secretion alongside stimulating insulin release
• Alpha cell insulin resistance is now recognized as a key pathophysiological component of T2DM, not just a secondary phenomenon

• Organic load (BOD - Biochemical Oxygen Demand)
• Temperature
• Microbial population density
• Oxygen availability
• Type of organic substrate

• Low organic load → oxidation completed closer to 8 hours
• High organic load → oxidation may extend to 16 hours
• The standard BOD₅ test (5-day BOD) measures oxygen demand over 5 days at 20°C, but actual biological oxidation in treatment plants is engineered to occur within hours through controlled conditions

NADH → Complex I → CoQ → Complex III → Cyt C → Complex IV → O₂
       (2.5 ATP)

FADH₂ → Complex II → CoQ → Complex III → Cyt C → Complex IV → O₂
         (1.5 ATP)

• Each NADH yields ~2.5 ATP
• Each FADH₂ yields ~1.5 ATP
• Total from one glucose: ~30-32 ATP

NADPH (HMP shunt) = biosynthesis and antioxidant defense NADH (glycolysis, PDH, TCA) = oxidative phosphorylation and ATP production

• Increasing intestinal glucose absorption
• Enhancing glycogenolysis (breakdown of glycogen)
• Increasing sensitivity to other hyperglycemic hormones (permissive effect)

"GECAT" - all cause hyperglycemia:
G - Glucagon         → glycogenolysis + gluconeogenesis
E - Epinephrine      → glycogenolysis + gluconeogenesis  
C - Cortisol         → gluconeogenesis (dominant effect)
A - Adrenal androgens (minor)
T - Thyroxine        → absorption + glycogenolysis ONLY

Glutamine + CO₂ + ATP
         ↓  [CPS II] ← Rate-limiting in mammals
    Carbamoyl phosphate
         ↓  [Aspartate transcarbamoylase] ← Rate-limiting in bacteria
    Carbamoyl aspartate
         ↓  [Dihydroorotase]
    Dihydroorotate
         ↓  [Dihydroorotate dehydrogenase] (only mitochondrial step)
    Orotate
         ↓  [Orotate phosphoribosyl transferase] ← option d
    OMP (Orotidine monophosphate)
         ↓  [Orotidylate decarboxylase] ← option a
    UMP → UDP → UTP → CTP

Stop codon enters A site
         ↓
Release factor binds A site (mimics tRNA structure)
         ↓
RF stimulates peptidyl transferase to act as hydrolase
         ↓
Water attacks peptidyl-tRNA bond (instead of aminoacyl-tRNA)
         ↓
Polypeptide chain released
         ↓
RF-3/eRF-3 (GTPase) facilitates RF dissociation
         ↓
Ribosome dissociates into subunits (recycling)

5'----[TTGACA]----17bp----[TATAAT]----~10bp----[+1 start]----3'
        -35 box              -10 box         Transcription
       (consensus)          (consensus)        begins here

"Prokaryotes use Consensus; Eukaryotes use TATA"