BIOCHEM final exam

3

enzyme definition

• intracellular

• plasma membrane

• complex enzyme = holoenyme with PROTEIN: APOENZYME and non portien component: COFACTOR

• prosthetic group:

• A type of cofactor (can be organic or metal) that is tightly or covalently bound to the enzyme.

• Unlike coenzymes, it does not dissociate easily.

• Example:

  • FAD in succinate dehydrogenase

Co enzyme = small organic molecule that is loosely bound to enzyme during reaction eg NAD or biotin

COFACTOR: non protein compound or metal ion that is required for an enzyme’s role as a catalyst

for exmaple:

mention cofactors for PDH complex

• for heme: porphoyrins (swap) (heme is tightly bound so its a prosthetic group)
  -quinones: upiquinone

• and a bunch of metal ions: zn,mg,cu

ENYZME CLASSIFICATIONS:

	Name	Simple Role
1	Oxidoreductases	Catalyze redox reactions (electron transfer)
2	Transferases	Transfer functional groups between molecules
3	Hydrolases	Break bonds using water (hydrolysis)
4	Lyases	Add or remove groups to form double bonds
5	Isomerases	Rearrange atoms within a molecule (isomerization)
6	Ligases	Join two molecules using energy (e.g., ATP)

ACTIVE SITE:
- complimentary

• binds to substrate via covalent. bonds

• active site formed during folding of tertiary and quaternary structure

• in cmplex enzymes cofactors are also part of it

• amino acid residues are found

ENZYME SPECIFICITY:

REACTION SPECIFICITY:
- enzymes catalYSE CERTAIN REACTIONS, DETERMINED BY THEIR PROTEIN CONTENT

substrate specificuty:
- fisger’s lock and key” associate correspondence between active site and substrate

koshland’s induced fit: activve site and substrate dont fit compeelt,y binding leads to conformational changes in bidning sit re

1

✅ Key Features:

• Tetrameric protein: LDH consists of four subunits.

• Two types of subunits:

  • H (Heart) type

  • M (Muscle) type

• and then state 5 LDH isoenzymes

heme: 4 subunits, 2a, 2b polypeptide chains

2 -

A chromosome is made of DNA tightly wrapped around histone proteins, forming nucleosomes.

• A nucleosome is DNA wrapped around a histone octamer (8 histone proteins).

• These nucleosomes coil and fold to form a chromatin fiber (about 30 nm thick).

• The chromatin fiber further loops and condenses to form the highly compact chromosome structure visible during cell division.

mRNA = carries genetic info from dna to rna for protein synth

• tRNA → brinds AA to ribosome during translaation

• rRNA → structure and fucntional unit of ribosomes

• miRNA = regulates gene expression

enzyme:

• as enzyme inc, velocity increaess, until substrate is lmiiting factor

• as substrate increases, so does rate (hyperbolic curve) until vMax is reached (Max velocity) → because enzyme is saturated

• same for ph, temp

5

🔹 1. Gene Expression (Enzyme Synthesis ↑ or ↓)

• The cell controls how much enzyme is made by regulating the expression of the gene that encodes the enzyme.

• If more enzyme is needed:

  • Transcription of the gene is increased → more mRNA → more enzyme produced.

• If less enzyme is needed:

  • Transcription is decreased → less mRNA → less enzyme made.

• Example:

  • In fasting, the gene for gluconeogenic enzymes is upregulated in the liver.

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🔹 2. Protein Degradation (Enzyme Breakdown ↑ or ↓)

• Enzymes can be actively degraded by the cell when they are no longer needed.

• This is done through:

  • Proteasomes (for cytosolic proteins).

  • Lysosomes (for membrane/secreted proteins).

• By increasing or decreasing the rate of enzyme degradation, the cell adjusts how much enzyme is available.

• Example:

  • Misfolded or damaged enzymes are rapidly degraded.

6 -

enzymes in diagnosis = used to find conc of x y z, (urine, plasma, gastric juice) and compare to normal value

8

vit D:

🦴 Vitamin D and Bone Remineralization

• Vitamin D (specifically calcitriol, the active form) increases calcium and phosphate absorption from the intestine.

• These minerals are essential for forming hydroxyapatite, the crystal that strengthens bone.

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🧬 Role of Osteoblasts

• Osteoblasts are bone-forming cells that:

  • Lay down new bone matrix (mainly collagen).

  • Promote mineralization by depositing calcium and phosphate into this matrix.

• Vitamin D stimulates osteoblasts to:

  • Express proteins like osteocalcin and alkaline phosphatase, which support mineral deposition.

9

maroergic bonds:
- ENOL PHOSPHATE = IN PEP

PHOSPHESTER = in creatine hosphate

• phosphoANHYDRIDE between 2nd and 3rd phosphate in ATP

ATP’S ENERGY IS REVERSIBLE!!!!!!!

atp hydrolised to adp + pi, energy can be used for x y z

BECAUSE adp to atp =

oxidative phsopyrlation (in mitoondria)

and substrate level phosphorylation (gluyolis)

COUPLING:

ATP → ADP + Pi (ΔG ≈ –30.5 kJ/mol)

This is coupled with various endergonic reactions, such as:

🧬 Example: Glucose phosphorylation
Glucose + Pi → Glucose-6-phosphate (ΔG > 0)
Coupled with:
ATP → ADP + Pi
→ Net reaction:
Glucose + ATP → Glucose-6-phosphate + ADP (ΔG < 0)

• Biological oxidation refers to the transfer of electrons (or hydrogen) from one molecule to another during metabolic reactions.

• It’s essential for energy production, especially in the form of ATP via the electron transport chain (ETC).

• Oxidation is always paired with reduction: one molecule loses electrons (oxidized), another gains them (reduced).

oxidoreductase: CATALYSE REDOX REACTIONS WHERE ELCTRONS, IN THE FORMOF H IS TRANSFERRED

📚 Subclasses of Oxidoreductases:

1. Dehydrogenases

   • Remove hydrogen atoms from substrates.

   • Often use NAD⁺/NADP⁺ or FAD as coenzymes.

   • Example: Lactate dehydrogenase

2. Oxidases

   • Transfer electrons to oxygen (O₂).

   • Example: Cytochrome oxidase (ETC complex IV)

🔋 Key Redox Systems & Their Roles

1. NAD⁺ / NADH

   • Catabolic reactions (e.g. glycolysis, TCA).

   • NAD⁺ → NADH carries electrons to ETC → ATP.

2. NADP⁺ / NADPH

   • Anabolic reactions (e.g. fatty acid synthesis).

   • NADPH used in biosynthesis & antioxidant defense.

3. FMN / FMNH₂

   • Part of ETC Complex I.

   • Accepts electrons from NADH.

4. FAD / FADH₂

   • In TCA cycle, β-oxidation, and ETC Complex II.

   • Electron carrier bound to enzymes.

5. Ubiquinone / Ubiquinol (CoQ)

   • Lipid-soluble ETC carrier.

   • Transfers electrons from Complex I/II → III.

6. Cytochromes (heme proteins)

   • In ETC Complex III & IV.

   • Transfer electrons via Fe³⁺ ↔ Fe²⁺.

7. Lipoate

   • Coenzyme in PDH & α-KGDH complexes.

   • Transfers acyl groups & electrons.

8. Ascorbate (Vitamin C)

   • Antioxidant, donates electrons.

   • Regenerates other antioxidants (e.g., vitamin E).

11 -

OXIDATIVE PHOSPH:

• Oxidative Phosphorylation

  • Occurs in mitochondria.

  • Electrons from NADH/FADH₂ pass through the electron transport chain (ETC).

  • Proton gradient drives ATP synthase → forms ATP.

  • O₂ is the final electron acceptor.

• Substrate-Level Phosphorylation

  • Occurs in glycolysis and TCA cycle.

  • ATP formed directly from high-energy intermediates.

  • Does not require oxygen or ETC.

15 -

citrate cycle - connection w carbs: CARBS BREAK DOWN TO FORM GLUCOSE, which forms pyruvate via glycolysis, which goes into the citrate cucle

DRAW CITRATE CYCLE AGAIN +

ENERGY BALANCE - 12 ATP (3 X 3NADH, 1 X FADH2, 1 ATP AT SUBSTRATE LEVEL)

REGULATION - ATP AND NADH INHIBIT!!!!! ADP AND NAD ACTIVATE

12

• flashcards suffice

13 -

thermogenesis = heat production in thermoregulation of warm blooded animals

regulated by:

CENTRAL/PERIPHERAL THERMORECEPTORS - detect blood temp changes

• hypothalmus - acts as a thermostat

ways of thermogenesis

ways that heat can be lost:

radiation, convection, condction, evaporation, lsotr htrough urine and feces

sympathetic reponse to cold:

• shivering

ALSO, due to cold exposure:

TRH, TSH, T3 IS RELEASED, increases adrenergic recprtor sensitivy

THERMOGENIN ROLE:
MEMBRANE PROTEIN IN BAT, bypasses ATP synthase, absorbs protons so can be converted to heat not stored as energy

• Plays a key role in non-shivering thermogenesis, especially in newborns and hibernating mammals.

brown adipocutes:

• polygonal, small structure with LIPID VACUOLE AND MANY MITCONDRIA WITH LOTS OF CRISTAE → with integral protein thermogenin.

OXIDASE:

• o2 = electron acceptor, but not incorporated as substrate eg cytochrome oxidase

PERIOXDASE:
- happen in peroxisomes, contain catalase and oxidase, used for BETA OX OF VERY LONG CHAIN FA

MICROSOMAL:

• occirs in ER, has cytochrome p450, requires NADPH

SHORT ELECTRON TRANSPORT;

• The endoplasmic reticulum (ER) contains electron transport chains involved mainly in detoxification and biosynthesis, unlike the long ETC in mitochondria for ATP production.

• These ER chains use cytochrome P450 enzymes,

14

metabolism:

anabolism

catabolism

pyruvate = 1 glucose, 2 pyruvate-

• anabolic synth of FA AND AA

• transferred to mitoondria for krebs

• in asbence of o2 forms lactate → can regenerate flucose

acteyl coa:

• product of beta ox of fatty acids, trasnproted by citrate shuttle to cytosol for fatty acid synth

• also used for krebs

• AVTICAES purivate dehydrogenase kinase

PHASES OF AEROBIC METABOLISM:

• DEG OF BIOPOLYMERS to monomores

• all momers are converted to acetyl coa

• - acteyl coa into krebs cycle to produce CO2 and H+

• H used for resp chain → (ETC)

citriate cycle: connection

GNERATING ENERGY THROUGH OXIDATION OF ACETYL COA

• TAKES PLACE IN MITOCONDRIA FOR EUKAROYTES, CYTOLPLAMS FOR PROKATYOTES.

• PRODUCES NADH AND AMINO ACIDS

REGULATION OF CITRATE CYCLE:

ALLOSTERIC INHIBITOR: ADP, NADH, ACGIVATOR = ADP.NAD

CONNECTION W LIPID METABOLSIM:
acetyl coa trasnfered via citrate shuttle to CYTOSOL FOR FATTY ACID SYNTH

CARB:
GLYCOLYSIS, PYRUVATE TO ACETYL COA

16

SALIVARY A AMYLASE:

• 1 4 GLYCOSIDIC BOND BROKEN

• POLYSACC TO DISACC

• ACINAR CELLS SECRETE PANCREATIC AMYLASE, BREAK DOWN DISACC TO MONO SACC

• GLUCOSE ABSORPTION IN ALL THE BODY PARTS DONT FORGET:

• IN LIVER: SITE OF GLYCOLISS + GNG, HAS GLYCOGEN STORES. ACTIVE PPP FOR SUPPLYING NADPH

• ERYTHROCYTES - NO ORGANELLES SO ANAEROBIC GLYCOLYSIS

• IN MUSCLES, can degrade carbs aeobically and anaerobically

• BRAIN ENTERS BRAIN VIA GLUC 1 + 3 → no PPP or GNG

• kindeys = GNG HAPPENS

lactase deficiency = lack of enzyme activity in kids

adults: change in control of gene expression

17 - glycolysis

• do scheme again

• anaerobic + aerobic

✅ Aerobic Glycolysis

• Occurs in the cytoplasm, not mitochondria.

• Glucose → Pyruvate (via glycolysis)

• Pyruvate enters mitochondria → converted to Acetyl-CoA

• Acetyl-CoA enters the citric acid cycle (TCA/Krebs cycle) → produces CO₂, NADH, and FADH₂

• These go to the electron transport chain, which produces H₂O and lots of ATP

👉 Yes, aerobic metabolism produces much more ATP (~30–32 ATP per glucose)

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✅ Anaerobic Glycolysis

• Happens in low oxygen conditions (e.g., active muscles)

• Glucose → Pyruvate → Lactic acid

• Occurs entirely in the cytoplasm

• Produces only 2 ATP per glucose

• SHUTTLES: MALATE ASP/GLYCEROL 3 PHOSPH AGAIN

PYRUVATE DEHYDROGENASE REACTION -

Regulated by phosphorylation:

• PDH kinase phosphorylates (inactivates) PDH

• PDH phosphatase dephosphorylates (activates) PDH

PDH CONVERTS PYRUVATE TO ACETYL COA

tissue specificity:

hexokinase - ALL CELLS

glycolysis happens in - skeletal muscle and blood cells

18 - GNG

• scheme again

• tissue specificity: FIRST ENZYME: PEP CARBOXYLASE = IN MITOCONDIRA, LAST ENZYME: GLUCOSE 6 POHSPHATSE IS IN ER, rest are cytoplasmic

regulation: insulin, glucagon + what hormones increase or decrease it

tissue localisation: TISSUE = 80, kidnye = 20

19 - ppp

• scheme

GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY: LEADS TO IMPRAIRMENT OF NADPH PRODUCTION, therefore h202 is not detoxified, so hemolytic damage happens

• lipid peroxidation happens: erythrocyte membrane breaks down and hemolytic anemia occurs

20 -

FRUCTOSE = HEXOSE SUGAR, MONOSACCARIDE

ABSORPTION:

ACTIVATION BY PHOSPHORYLATION BY

• hekokinase, glucokinase, fructokinase, galactokinase

• furthered by glyc, glyc, aldolase, galactose metabolism

L + M

L + K

L

L

fructosuria = DEFICIENCY OF FRUCTOKINASE THEREFORE INCREASED FRUCTOSE IN BLOOD AND URINE

FRUCTOSE INTOLERANCE:

• due to aldolase b AFFECTING KINDEY

• DEPOSITION OF FRUCTOSE 1 PHOSPHATE IN LIVER, INHIBITS FRUCTOKINASE - CAN CAUSE SLIGHT INCREASE IN BLOOD SUGAR

GALACTOSEMIA 1

Galactosemia Type I (Classic Galactosemia)

• Enzyme deficiency: Galactose-1-phosphate uridyltransferase (GALT)

• Accumulated substance: Galactose-1-phosphate

• Symptoms (after milk ingestion):

  • Vomiting

• GALACOSEMIA 2:
  Galactosemia Type II

  • Enzyme deficiency: Galactokinase (GALK)

  • Accumulated substance: Galactose
    (gets converted to galactitol, especially in the lens)

  • Main symptom: Cataracts

GALACTOSE TRANSPORT: Galactose is absorbed across the apical membrane of enterocytes via sodium-dependent cotransport (SGLT-1), and then transported across the basolateral membrane into the bloodstream via GLUT2.

21 - glycogen metabolsim

STRUCTURE:
- POLYMER OF GLUCOSE

• A-14, 1-6 GLYCOSIDIC BONDS

• BRANCHED OR UNBRANCHED

• sphere shape

degradation:

glyc phosph - breaks 1-4 bond

glucose 1 phosphate is released

glygoen remodelled

gluc 1 phoph to gluc 6 phohsp for further metabolsim

REG ENZYMES: AS YOU EXPECT glucogen synthase, phpsphorylase

INCLUDE INSULIN AND GLUCAON

STORAGE DISEASE:

von gierke - hypoglycemia

ANDERSONS - liver dysfunction

MC,CARDLES - muscle cramps

MUSCLE defic of PFK - inab to excersie

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• just like evrything abt glucose

• hypoglycemia:
  - fasting, skipping meals, excess insulin, alcohol intake/adrenal insufficiency

hyperglycemia: type ½ diabetes mellitus

lipids:

• Sphingosine + fatty acid = Ceramide (the core of all sphingolipids)

• Ceramide + head group = Sphingolipid (e.g., sphingomyelin, cerebrosides, gangliosides)

lipoprotein = non polar lipid core with APOLIPOPROTEIN ON SURFACE

VLDL/LDL/HDL/IDL/CHYLOMICRON

GLYCEROL METABOLISM: FIRST ENZYME???

(ADIPOSE TRYGLYCERIDE LIPASE)

24 - TAG

• schemes (DHAP and glycerol)

• fate of fatty acids

• regulation: insulin/glycagon

insulin:

increased Pyruvate dehydrog - > inc acetyl coa - > citrate shuttle: INC SUBSTRATE FOR FATTY ACID SYNTH

glucagon:

• lipolysis: acetyl coa carboxylase inactive

25 -

• fa to acyl coa

• carnitine shuttle

• even synth (acyl coa to acetyl coa + acyl coa)

odd:

propinoyl + POLYUNSATURATED FAT

-r egulation = cpt high = starving and vice versa

energy balance (Mol atp_

and number of atp produced per cycle

7 BETA OX. 7 NAD/FAD AND 8 ACTEYL COA. actetyl coa = 10, nad = 3, fad = 2

REGULATION: INSULIN REDUCES CPT1 REMEMBER

ALLOSTERIC INHIBITO: MALONYL COA FFA SYNTHASE

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• REGULATION:

• Insulin:It promotes fat storage (lipogenesis) and inhibits lipolysis, so fewer free fatty acids are released from adipose tissue.
  → Result: Less substrate (acetyl-CoA) available for ketone body production in the liver.

• → Correction: HMG-CoA synthase is the key step insulin inhibits to reduce ketone production.

• Glucagon: Glucagon promotes ketogenesis by stimulating the release of fatty acids from adipose tissue and increasing causing their BETA OX TO FORM ACETYL COA.Glucagon also activates the enzyme HMG-CoA synthase, which is crucial for ketone body production.

• Ketosis: A metabolic state where the body uses fat instead of carbohydrates for energy, producing ketone bodies. Occurs during prolonged fasting, low-carb diets, or uncontrolled diabetes.

• Ketonuria: Presence of ketone bodies in the urine. It's a sign the body is in ketosis and can be detected using urine dipsticks.

• Ketoacidosis: A serious complication (most common in uncontrolled Type 1 diabetes) where excessive ketones make the blood acidic. It can be life-threatening and requires urgent treatment.

Ask ChatGPT

27 - my bday so fatty

MAAA (CALLING MA WHATS FOR DINNER = MALONYL COA + ACYL COA)

Adipose

Stores FAs as TAGs; releases FAs during fasting.

Muscle

Oxidizes FAs for energy (esp. during fasting).

• Stearate (C18:0) → Oleate (C18:1, Δ⁹) via Δ⁹-desaturase

fatty acid bio ox = IN MITOCOHONDRIA

fatty acid sunth = IN CYTOPLASM

Elongated → using elongase enzymes (adds 2C units)

• Desaturated → using desaturase enzymes to insert cis double bonds at specific positions (like Δ⁹, Δ⁶, Δ⁵)

INSULIN AND GLUCAGON REGULATE

28 - PHOSPHOLIPIDS

DE NOVO SYNTH: STARTS WITH DHAP ALMOST IDENTAICAL TILL DAG 3P

P1 = GLYC AND FA IN 1ST PLACE

G AND FA IN 2ND PLACE

C = GLYCEROL AND PHOSPHORIC ACID

ALCOHOL AND PHOSPHORIC ACID

Sphingolipidoses

LYSOSOME STORAGE DISORDER, DEFECTS IN ENZYMES,CUSES ACUCULATION

eg niemman pick → built up o sphynigomyelin, bc of def of sph = myelinase. CHERRY RED SPOT AND FOAM CELLS

29 =

nsaid = ncs = N and c

NSAID = CYCLO OX (COX 1 AND 2)= INHIBITED. THEREFORE JUST PROSTAGLANDINS DECREASE

said = lipox

inhibits phospholipase 2, reduces prostaglandins and leukortienes

BLOOD PRESSURE REGULATION:

Prostacyclin (PGI₂) → vasodilation, inhibits platelets

• Thromboxane A₂ (TXA₂) → vasoconstriction, promotes platelets

MAIN REGULATION:

• PLIPASE 2 = key ENZYME FOR BOTH, BUT COX IS MAIN ENZYME FOR COX, LOX IS MAIN ENZYME FOR LOX (they convert arachidonic acid into each of the enzyme)

ADRENALINE ACTIVTOR FOR PLIPASE A2

CORITOSTEROIDS = INHIBITOR FOR PLIPASE 2

but inhibitor for COX = nsaid

Feature	SAIDs (Steroids)	NSAIDs
Inhibit	Phospholipase A2	COX-1 and COX-2
Effect	↓ Prostaglandins & leukotrienes	↓ Prostaglandins
Examples	Cortisol, Prednisone	Ibuprofen, Aspirin, Naproxen
Action Level	Upstream (broad anti-inflammatory)	Downstream (specific to prostaglandins)

30 - cholesterol

HMG COA REDUCTASE!!!!! IS REG ENZYME

reverse compettive inhibition through statins

long term an short term inhibitors:

• include cholesterol moving stuff

REVERSIBLE COVALENT MODIFICATION = ACTIVE IN DEPHOSPH FORM

reversible competitive inhibition = statsin

include transport;!!!!!!!

31 - chol derivatives

• FORGOT:

• LOCALISATION OF EACH

• bile acids = primary in liver, seconary in intestine

• 7a hydroxylase = main enzyme

• function: INHIBIT CHOL SYNTH VIA INHIB O HMG COA REDUCTASAE

• inhib: bile acids

• activators: cholesterol

steoird hormone:

• 4 fused rings, cyclophenthanjsfgsd nucelus

• REGULATION: DESMOLASE P450

vit d3:

• skin, liver, kidney

• substrate = 7dehydrocholesterol

32

transaminase =transamination is when an amine group is transferred from an amino acid to a keto acid forming a new keto acid and new amino acid

oxidative deamination: It is the removal of an amino (–NH₂) group from an amino acid, usually glutamate,

• The amino group is replaced with a keto group, forming α-ketoglutarate.

• The released ammonia (NH₃) enters the urea cycle for excretion.

• Catalyzed by glutamate dehydrogenase

• Occurs mainly in the liver mitochondria

decarboxylation: removal of carboxyl group, released as co2

biogenic amines: hisitidine, forms histamine → allergic

TRANSDEAMINAITON:

• Transamination

  • Amino group from an amino acid is transferred to α-ketoglutarate, forming glutamate

  • Catalyzed by aminotransferases

• Oxidative Deamination

  • Glutamate is then deaminated by glutamate dehydrogenase

  • Produces ammonia (NH₃) and α-ketoglutarate (which can be reused

33 -

REDUCTIVE AMINATION OF AKG:
AKG + NH2 + NADPH → GLUTAMATE

emzyme = glutamate dehyrogenase

adds ammonia to a keto acid forming amino acid

important for amino acid biosynth

GLUTAMINE SYNTH:

glutamate + nh2 + atp =. glutamate

glutamine synthetase

glutamine =non toxic ammonica carrier, carries it to kidneys to be extreted

AMMONIOGENESIS IN KIDNEYS:

GLUTAMINE in prox tubules is borken down to give nh3

binds w h+ in urine, forms ammonia HWIHCH IS EXCRETED

MAINTAINS ACID BASE BALANCE

urea cycle:

1. Ammonia + CO₂ → Carbamoyl phosphate

2. Citrulline → Argininosuccinate → Arginine → Urea + Ornithine

   REGULATION: CP1 = RATE LIMITING, NAG activates

deficinecy:

CP1, REDICED C PHOSPH SNTHETASE 1, LEADS TO HYPERAMMONIA TYP1 , AND VOMITING, CEREBREAL EDEMA

• GLUCOSE ALANINE: exetes nitrogen from muscles, presents c skeleton of muscles to liver for glucose prof

35

ONE CARBON RESIDUES ARE:

eg co2 for carboxylation

or formyl for purine ring forming

• used for synthesis of serine and methionine

• synthesis of TMP from dUMP - further in DNA synth

• synthesis of pruine nucleotides - further in DNA and DNA synthesis

SAM:

• PHOSPHLIPD METABOLISM

• dna/rna methylation

• neurotransmitter sunthsesis

FOLIC ACID:

ACTIVE FORM, amino acid metab, carries one carbon unit, METHYLATES VIT 12

• PURINE AND THYMIDINE SYNTHESIS

VIT B12:

ACCEPTS VIT B12

• remethylates homocysteine forming METHINONINE

• convert methyl malonul coa to succinyl coa

36 -

creatnie phosphate:

ARGININE, GLYCINE, SAM

• L- ARGININE = precursor for polyaminesL spremidine and spermine = for ribosome formataion

• cationic compound used to bind RNA AND DNA

phospholipids:

1. Ethanolamine & Choline (from serine):

• Serine → Ethanolamine (via decarboxylation)

• Ethanolamine → Choline (after methylation by SAM)

SPINGOLOPIDS:
SERINE + PALTMIOYL COA = soinhgosine

spingospine + FA = ceramide etc (head fgroup_

MELATONIN:

• OBTAINED BY METHYLATION OF SEROTIN (also serotinin = PLATELET AGGREGATION + SMOOTH MUSCLE CONTRCT)

glutamate: OX DEAM:

• removal of amine group, replaced with keto group, ammonia recycled into urea cycle

• glutathione:

• antioxidant, detoxifies xenobiotics, donor of H+ in reductive reactions, transport amino acids

creatine phosphate:

made by

• Arginine

• Glycine

• S-adenosylmethionine (SAM)

using creatine kinasae.

• role = energy reserve in muscles

citruline: (used for) nitrogen metabolism, especially in the urea cycle

• arginine + NO synthase is required

• NO is byproduct of the reaction + seconary messenger

• leads to vasodilation of BV

• a gas that diffuses through the membranes and reaches the smooth muscle

42 -

✅ Connection Between Lipid and Carbohydrate Metabolism – Corrected Explanation

1. β-Oxidation of Fatty Acids

   • Fatty acids are broken down via β-oxidation in the mitochondria.

   • This produces acetyl-CoA, NADH, and FADH₂.

   • Acetyl-CoA enters the Krebs cycle, generating ATP.

   • The ATP and NADH produced support gluconeogenesis (even though acetyl-CoA itself can’t become glucose).

2. Acetyl-CoA does not contribute carbon to gluconeogenesis

   • Instead, it activates pyruvate carboxylase, promoting gluconeogenesis from pyruvate, lactate, glycerol, or amino acids.

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3. Excess Carbohydrate → Lipid Synthesis

   • Glucose → pyruvate (via glycolysis)

   • Pyruvate → acetyl-CoA (via pyruvate dehydrogenase in mitochondria)

   • Acetyl-CoA can’t cross the mitochondrial membrane directly, so:

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4. Citrate Shuttle (not "saturated shuttle")

   • Acetyl-CoA combines with oxaloacetate → citrate

   • Citrate is transported to the cytosol

   • In the cytosol, ATP-citrate lyase converts citrate → acetyl-CoA + oxaloacetate

   • Now, cytosolic acetyl-CoA is used for fatty acid synthesis

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beta ox of fatty acids: D,H,D,T ( AH, THE KILLER) (fadh2, h20, nadh2, thiolase)
(My kangaroo has three arms = FA SYNTH)

COASH + H20, NADHPH TO NADP, H20, NADPH + NADP

• proteins: metabolism to amino acids

• amine groups are removed from glutamate, replaced with ketone, forming ammonia to be recycled into urea cycle

47 - signal transduction

intracellular signalling = simple (ligand binds to receptor) etc

intercellular = chemical synapse thingy.\

• RECEPTORS:

• warer so;uble/lipid soluble

• A lipid-soluble hormone (e.g., steroid or thyroid hormone) diffuses across the cell membrane.

• It binds to an intracellular receptor, forming a hormone-receptor complex.

• This complex enters the nucleus and binds to specific DNA sequences (hormone response elements).

• It acts as a transcription factor, modifying gene expression.

• This leads to the production of new proteins, which bring about specific cellular responses.

✅ Protein Kinases

• Enzymes that add phosphate groups (phosphorylate) to proteins, usually on serine, threonine, or tyrosine residues.

• This often activates or deactivates the target protein, altering its function or activity.

• Example: Protein kinase A (PKA) activated by cAMP.

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✅ Protein Phosphatases

• Enzymes that remove phosphate groups (dephosphorylate) from proteins.

• Oppose the action of kinases; help turn off signals or return proteins to baseline activity.

• Example: Protein phosphatase 1 in glycogen metabolism.

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✅ G-binding Proteins (G-proteins)

• Act as molecular switches in signal transduction.

• Bind GTP (active) and GDP (inactive) forms.

• Involved in transmitting signals from GPCRs (G-protein-coupled receptors) to enzymes like adenylyl cyclase or phospholipase C.

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🧠 In summary:

• Kinases = add phosphate → modify activity

• Phosphatases = remove phosphate → reverse effect

• G-proteins = switch proteins that relay signals inside the cell

• __________

• Amplification: One signal activates many downstream molecules → bigger response.

• Convergence: Different signals activate the same pathway or target.

• Divergence: One signal activates multiple pathways or targets.

• Integration: Multiple signals are combined and processed into a single response.

• Crosstalk: One signaling pathway affects or interferes with another.

48 -

• synapses

• g protein coupled receptors yk (Used by water-soluble molecules (e.g., adrenaline, glucagon), which cannot cross the membrane.

• The ligand binds to an extracellular domain of the GPCR, causing a conformational change.

• This activates the G-protein, which transmits the signal to effectors like adenylyl cyclase.

• Adenylyl cyclase converts ATP to cAMP → cAMP activates protein kinase A (PKA).

• PKA phosphorylates target proteins (often on serine or threonine residues), leading to specific cellular responses.)

• enzyme linked with activity:
  3. Enzyme-Linked Receptors / Receptors with Intrinsic or Associated Enzyme Activity

  • Ligand binding directly activates enzyme activity of the receptor (e.g., receptor tyrosine kinases) or of an associated protein.

  • Leads to phosphorylation cascades, commonly involved in growth, metabolism, and cell division.

  • Example: Insulin receptor (has intrinsic tyrosine kinase activity).

• ALL THE SECONDARY MESSENGERS:

• ypes of Second Messengers (Mediators)

  • cAMP (cyclic AMP)

    • Activates protein kinase A (PKA).

    • PKA phosphorylates various proteins, leading to diverse cellular responses like metabolism regulation.

  • Nitric Oxide (NO)

    • A gaseous signaling molecule.

    • Causes vasodilation by relaxing smooth muscle.

    • Activates guanylyl cyclase, increasing cGMP levels inside cells.

  • cGMP (cyclic GMP)

    • Generated by guanylyl cyclase activation (often by NO).

    • Activates protein kinase G (PKG).

    • Involved in smooth muscle relaxation and other signaling pathways.

  • IP3 (Inositol Triphosphate)

    • Produced by cleavage of PIP2 by phospholipase C.

    • Releases Ca²⁺ from intracellular stores (endoplasmic reticulum).

  • DAG (Diacylglycerol)

    • Also produced from PIP2 cleavage by phospholipase C.

    • Activates protein kinase C (PKC), which phosphorylates target proteins.

  • Calcium (Ca²⁺)

    • Acts as a universal second messenger.

    • Binds to calmodulin, forming a complex that activates enzymes like myosin light chain kinase (MLCK).

    • Important in smooth muscle contraction and many other processes.

  • Calmodulin

    • A calcium-binding protein that transduces the calcium signal by activating target enzymes.

  • PIP3 (Phosphatidylinositol Triphosphate)

    • Generated by phosphorylation of PIP2 by PI3 kinase.

    • Recruits and activates signaling proteins like AKT (protein kinase B), involved in cell growth and survival.

  ---

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49 -

• put your classification

• mechanism of action

• regulation

• Mediators are substances that act locally (usually near where they are produced

Common Types of Mediators

• Eicosanoids: (also a lipid-soluble hormone type)

  • Prostaglandins

  • Leukotrienes

  • Thromboxanes

  • They are involved in inflammation, pain, fever, and blood clotting.

• Cytokines:

  • Small proteins involved in immune responses.

  • Examples: Interleukins, interferons, tumor necrosis factors.

• Nitric Oxide (NO):

  • A gaseous mediator.

  • Acts as a vasodilator and neurotransmitter.

• SYNTHEISS AND DEGRADATION:
  

• Catecholamines (like adrenaline) are synthesized from amino acid precursors (like tyrosine).

• Degradation:

  • Water-soluble hormones are usually degraded by enzymes in blood or target tissues and cleared by kidneys/liver.

  • Lipid-soluble hormones are metabolized primarily in the liver and excreted in bile or urine.

50 - hormones of hypothalamus and pituitry

you know EVERYTHING:
only thing is mechanism of action: ANTERIOR:
CRH → binds pituitary corticotrophs → stimulates ACTH release → ACTH binds adrenal cortex receptors → activates cAMP → cortisol synthesis.

Mechanism of Action: oF POSTERIOR PITUARITRY GLAND

• Both hormones bind to GPCRs on target cells.

• Oxytocin → increases intracellular Ca²⁺ in uterine muscle cells → contraction.

• ADH → activates cAMP → insertion of aquaporin channels in kidney → water retention.

51 -

everything you know

steroids = androstene/dhap from zona reticularis

testosterone/esterogen from ovarys

mechanism of action = just lipid soluble ones

52 - water

• Renin release:

  • Juxtaglomerular cells in the kidney secrete renin into the bloodstream.

• Angiotensinogen conversion:

  • Renin cleaves angiotensinogen (produced by the liver) → angiotensin I.

• Formation of angiotensin II:

  • Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE), primarily in the lungs (not hypothalamus).

• Effects of angiotensin II:

  • Potent vasoconstrictor, increasing blood pressure.

  • Stimulates secretion of aldosterone from the adrenal cortex (zona glomerulosa).

  • Stimulates release of ADH (vasopressin) from the posterior pituitary.

  • Stimulates thirst center in the hypothalamus.

• Aldosterone action:

  • Acts on the distal convoluted tubule and collecting duct in the kidney.

  • Increases sodium reabsorption (and water follows osmotically).

• NAP:

• Produced by the heart (atrial natriuretic peptide - ANP) and ventricles (brain natriuretic peptide - BNP).

• Released in response to increased atrial stretch (high blood volume).

• Actions:

  • Promote vasodilation.

  • Inhibit renin, aldosterone, and ADH secretion.

  • Increase sodium and water excretion by kidneys (natriuresis and diuresis).

• Overall effect: reduce blood volume and pressure.

53

INSULIN:

• GLUCOSE UPTAKE INC VIA GLUT 4

• stimulates lipgenesis and tag formation (draw tag synth)

• acetyl coa carboxylase is ACTIVATEDM forming more malonyl coa, which inhibits beta ox, meaning less acetyl coa SO KETOGENESIS IS INHIBITED (provides alternative fuel for brian via degredation of acetyl coa, stimulated when glucose is LOW)

• less krebs cycle = less atp for GNG

• stimualtes glycogenesis (formation of glycogen) -

• INHIBTIS GNG

• stimulates glycolysis

opposite for glucagon:

• Glucagon promotes lipolysis → increases free fatty acids.

• Inhibits acetyl-CoA carboxylase → lowers malonyl-CoA → enhances β-oxidation.

• Increased acetyl-CoA → supports ATP production and ketone body synthesis.

• These processes provide energy during fasting/low glucose and help maintain glucose homeostasis.

somatostatin:

🧠 Hypothalamus

• Secreted by hypothalamic neurons.

• Inhibits growth hormone (GH) release from the anterior pituitary.

• Also inhibits TSH to some extent.

• and pancreatic polypeptide

mechanism of action:

GLUCAGON:

binds to GPCR, G PROTEIN ACTIVATED, ACTIVATEDS ADNELYL CYCLASE, THEREFORE CAMP, THEREFORE PKA, ACTIVATES GLYCOGEN PHOPSHYRLASE AND INHIBTS GLYCOGEN SYNTHASE

insulin:

Insulin binds to its extracellular receptor, activating the receptor’s intrinsic tyrosine kinase activity. This leads to autophosphorylation of the receptor and phosphorylation of insulin receptor substrates (IRS). The activated IRS triggers downstream signaling pathways that stimulate glycogen synthesis (glycogenesis), glucose uptake, protein synthesis, and lipid synthesis.

54

pre cholinergic symp fibres

55 -

Types of Diabetes Mellitus

1. Type I Diabetes Mellitus (T1DM)

   • Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency.

   • Onset usually in childhood/adolescence.

   • Requires lifelong insulin therapy.

2. Type II Diabetes Mellitus (T2DM)

   • Combination of insulin resistance and relative insulin deficiency.

   • Strong link to obesity, sedentary lifestyle, and genetics.

   • Managed by lifestyle, oral hypoglycemics, sometimes insulin.

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🔬 Metabolic Disorders in Diabetes

• Carbohydrate metabolism:

  • ↓ Glucose uptake in tissues → hyperglycemia

  • ↑ Gluconeogenesis and glycogenolysis (especially in T1DM)

• Lipid metabolism:

  • ↑ Lipolysis → ↑ free fatty acids → ketogenesis (especially in T1DM)

  • Risk of diabetic ketoacidosis (DKA)

• Protein metabolism:

  • ↑ Proteolysis → muscle wasting

  • Impaired protein synthesis

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🚨 Symptoms of Diabetes

• Classic triad:

  • Polyuria (frequent urination)

  • Polydipsia (increased thirst)

  • Polyphagia (increased hunger)

• Weight loss (T1DM), fatigue, blurred vision

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⚠ Complications of Chronic Hyperglycemia 1. Oxidative Stress

• High glucose → overproduction of reactive oxygen species (ROS) in mitochondria.

• Leads to cellular damage, inflammation, endothelial dysfunction.

• Central in the development of complications (neuropathy, nephropathy, retinopathy).

2. Sorbitol Pathway

• Excess glucose converted to sorbitol by aldose reductase.

• Sorbitol accumulates in cells (esp. lens, nerves) → osmotic stress → cataracts, neuropathy.

3. Non-enzymatic Glycation – AGE & RAGE

• Chronic hyperglycemia → spontaneous glycation of proteins → Advanced Glycation End-products (AGEs).

• AGEs bind to RAGE receptors on cells → trigger inflammation, fibrosis, and vascular damage.

• Key in microvascular and macrovascular complications.

4. DAG/PKC Pathway

• High glucose increases diacylglycerol (DAG) → activates protein kinase C (PKC).

• PKC affects blood flow, increases vascular permeability, inflammation, and thrombosis.

• Promotes retinopathy, nephropathy, atherosclerosis.

🔬 1. Connective Tissue: Overview

Connective tissue supports and connects other tissues and organs. It consists of:

• Cells

• Extracellular matrix (ECM): made of fibers (proteins) and ground substance (GAGs + proteoglycans)

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🧫 2. Cell Types in Connective Tissue

• Fibroblasts: Main ECM-producing cells; synthesize collagen, elastin, GAGs, proteoglycans.

• Macrophages: Phagocytic immune cells.

• Mast cells: Release histamine and play a role in inflammation.

• Adipocytes: Store fat.

• Plasma cells and leukocytes: Immune defense.

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🧱 3. Extracellular Matrix (ECM)

The ECM provides structural support, biochemical signals, and regulates cell behavior.

Components:

• Fibrous proteins: Collagen, elastin, fibronectin, fibrillin

• Ground substance: GAGs and proteoglycans

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🧬 4. ECM Proteins: Structure & Function ✅ Collagen

• Function: Provides tensile strength

• Structure: Triple helix of three α-chains

• Synthesis: In fibroblasts → pro-collagen → secretion → extracellular modification (cross-linking)

• Types:

  • Type I: Bone, skin, tendon

  • Type II: Cartilage

  • Type III: Reticular fibers (skin, blood vessels)

  • Type IV: Basement membrane

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✅ Elastin

• Function: Elasticity to tissues (skin, lungs, arteries)

• Structure: Hydrophobic, random coil protein; cross-linked via desmosine

• Synthesized as tropoelastin, then cross-linked extracellularly.

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✅ Fibronectin

• Function: Cell adhesion, migration, wound healing

• Structure: Dimer linked by disulfide bonds; contains RGD (Arg-Gly-Asp) sequence for integrin binding

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✅ Fibrillin

• Function: Forms microfibrils for elastin deposition; structural support

• Important in Marfan syndrome (mutation in FBN1 gene)

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🧪 5. Glycosaminoglycans (GAGs) Structure:

• Long, unbranched polysaccharides

• Composed of repeating disaccharide units (amino sugar + uronic sugar)

• Highly negatively charged → attract water

Types and Functions:

GAG	Location	Function
Hyaluronic acid	Synovial fluid, ECM	Lubrication, space filler

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🧬 6. Proteoglycans Structure:

• Core protein + covalently attached GAG chains

• Highly hydrated → gel-like matrix

Functions:

• ECM structure

• Regulate molecule diffusion

• Bind growth factors

• Signal transduction

Examples:

• Aggrecan (in cartilage)

• Perlecan (in basement membranes)

🦴 1. Biochemical Composition of Bone

Bone is a specialized connective tissue composed of:

a) Organic Matrix (~30%)

• Type I collagen (~90% of organic content): provides tensile strength

• Non-collagen proteins: osteocalcin, osteonectin, osteopontin – involved in mineralization and cell signaling

b) Inorganic Matrix (~70%)

• Hydroxyapatite crystals:₂

  • Provides rigidity and hardness

• Contains calcium, phosphate, magnesium, fluoride

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🔬 2. Molecular Organization

• Osteoblasts: Build bone; secrete osteoid (unmineralized matrix)

• Osteocytes: Mature bone cells; maintain bone matrix

• Osteoclasts: Resorb bone; multinucleated cells that secrete acids and enzymes

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🔁 3. Bone Metabolism

Bone is constantly remodeled through:

• Bone formation by osteoblasts

• Bone resorption by osteoclasts

Key processes:

• Collagen synthesis (procollagen → tropocollagen → fibrils)

• Mineral deposition into the collagen matrix

• Matrix degradation during bone resorption (enzymatic and acidic)

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🧪 4. Bone Mineralization – Main Mechanisms

• Initiated by osteoblasts

• Secretion of alkaline phosphatase (ALP) → increases local phosphate levels

• Calcium and phosphate ions crystallize to form hydroxyapatite

• Matrix vesicles serve as initial sites for crystal nucleation

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58 -

1. Biochemistry of Blood

Blood is a specialized connective tissue composed of:

• Plasma (fluid matrix): ~55% of blood volume, containing proteins (albumin, globulins, fibrinogen), electrolytes, nutrients, hormones, and waste products.

• Formed elements (~45%): Red blood cells (RBCs), white blood cells (WBCs), and platelets.

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2. Types of Blood Cells

1. Red Blood Cells (Erythrocytes)

2. White Blood Cells (Leukocytes):

   • Granulocytes: Neutrophils, Eosinophils, Basophils

   • Agranulocytes: Lymphocytes, Monocytes

3. Platelets (Thrombocytes)

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3. Red Blood Cells (RBCs / Erythrocytes) Characteristic Features

• Biconcave, anucleate cells specialized for oxygen transport via hemoglobin (Hb).

• Lifespan: ~120 days.

• Lack mitochondria: rely entirely on anaerobic glycolysis for ATP production.

• "CO₂ is transported in the blood mainly as bicarbonate (via carbonic anhydrase), and some CO₂ also binds directly to hemoglobin to form carbaminohemoglobin."

Metabolic Pathways in RBCs

1. Glycolysis (Embden-Meyerhof pathway) – main ATP source.

2. Pentose Phosphate Pathway (PPP) – produces NADPH, essential for reducing glutathione, protecting RBCs from oxidative damage.

Enzymopathies

Inherited enzyme deficiencies affecting RBC metabolism:

• G6PD deficiency (PPP): ↓NADPH → oxidative stress → hemolysis.

• Hexokinase deficiency: rare, affects glycolysis initiation.

Anemias

• Hemolytic anemia: due to RBC destruction (e.g., enzymopathies, sickle cell anemia).

• Iron-deficiency anemia: ↓Hb synthesis.

• Megaloblastic anemia: due to folate/B12 deficiency.

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4. White Blood Cells (Leukocytes) Types & Roles

Type	Category	Function
Neutrophils	Granulocyte	Phagocytosis, first responders to infection
Eosinophils	Granulocyte	Defense against parasites, allergy mediator
Basophils	Granulocyte	Release histamine in allergic reactions
Lymphocytes	Agranulocyte	T cells (cell-mediated immunity), B cells (antibody production)
Monocytes	Agranulocyte	Become macrophages; phagocytosis, antigen presentation

Metabolic Features

• Unlike RBCs, WBCs have nuclei and mitochondria.

• Use both aerobic and anaerobic metabolism.

• Neutrophils rely more on glycolysis and PPP for ROS generation (via NADPH oxidase).

• Lymphocytes show increased metabolic activity upon activation (e.g., glycolysis and oxidative phosphorylation).

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5. Phagocytosis (Brief)

A key immune process primarily carried out by:

• Neutrophils

• Monocytes/macrophages

Steps in Phagocytosis

1. Recognition of pathogens via surface receptors (e.g., Fc, complement receptors).

2. Engulfment forming a phagosome.

3. Fusion with lysosome → phagolysosome.

4. Killing and digestion via:

   • Reactive oxygen species (ROS) – generated by NADPH oxidase (respiratory burst).

   • Hydrolytic enzymes – degrade engulfed particles.

59

whole cascade + plasma proteins + firbonylyisis

Vitamin K is essential for the γ-carboxylation of glutamate residues in clotting factors II, VII, IX, X, and proteins C and S. This modification allows these proteins to bind calcium ions, which is necessary for their activation and function in the coagulation cascade.

61-

• GNG - carb

• fatty synth - lipid

• proteins: deamination

extretory function:

bile - functiosn

specific products:

• albumin, clotting factors

• ketone

✅ Corrected Brief Definition:

Oxidative deamination is the process by which the amine group (-NH₂) is removed from glutamate, forming a keto acid (α-ketoglutarate) and free ammonia (NH₃). This reaction is catalyzed by the enzyme glutamate dehydrogenase, primarily in the liver.

. Biotransformation of Xenobiotics

• Phase I: Modification (oxidation, reduction, hydrolysis) mainly by cytochrome P450 enzymes.

• Phase II: Conjugation (glucuronidation, sulfation, etc.) to increase solubility for excretion.

5. Ethanol Metabolism

• Occurs mainly in the liver:

  • Alcohol dehydrogenase: Ethanol → Acetaldehyde

  • Aldehyde dehydrogenase: Acetaldehyde → Acetate

• Produces NADH, which can disrupt normal metabolism (e.g., fatty liver, lactic acidosis).