Biochemistry II: Pathways, Signaling, & More

Pyruvate dehydrogenase complex (PDH)

E1 — Pyruvate Dehydrogenase (B1)

E2 — Dihydrolipoyl Transacetylase (B5, Lipoic A.)

E3 — Dihydrolipoyl Dehydrogenase (B2, B3)

Citric acid cycle

GLUT proteins

GLUT-1: RBCs, Brain, Adipose T.

GLUT-2: Liver, Pancreas (β-cells), Kidney

GLUT-3: Brain (neurons)

GLUT-4: Muscles, Adipose T. [INSULIN DEPENDENT]

GLUT-5: Fructose transporter

Glycolysis

Glycerol-phosphate shuttle

Malate-aspartate shuttle

Gluconeogenesis

Cori cycle

Glucose-alanine cycle

Glycogenesis

Glycogenolysis

Pentose phosphate pathway

Fatty acid degradation

Fatty acid synthesis

Citrate-cleavage pathway

Synthesis of triacylglycerols

Ketogenesis

Utilization of ketone bodies

Synthesis of leukotrienes and prostaglandins

Mevalonate pathway

Vitamin D3 synthesis

Bile acid synthesis

Oxidative decarboxylation of amino acids

Monooxygenation of amino acids

Glutathione pathway

γ-glutamyl cycle

Transamination of amino acids

Oxidative deamination of amino acids

Urea cycle

C1 transfer

De novo purine synthesis

Salvage pathways in purine metabolism

De novo pyrimidine synthesis

Mercapturate pathway

Heme synthesis

Essential amino acids

PVT TIM HALL

Phenyalanine

Valine

Threonine

Tryptophan

Isoleucine

Methionine

Histidine

Arginine

Leucine

Lysine

Conditionally non-essential amino acids

GCG PT

Glutamine

Cysteine

Glycine

Proline

Tyrosine

Non-essential amino acids

SAAAG

Serine

Alanine

Asparagine

Aspartate

Glutamate

Degradation of purine nucleotides

Monomeric G-proteins

RAS: MAPK Pathway (starting with RAF)

RAB: Regulate vesicular transport b/w organelles

RAC: Regulate cytoskeleton, motility, and cell shape

RAN: Nuclear transport, RNA processing, mitosis

Nitric oxide pathway

Insulin pathway

JAK/STAT pathway

TGF-β pathway

Cell cycle (& cyclins)

G1-G1/S phase pathway

G2/M phase pathway

Post S phase pathway

Healthy vs cancerous cells

Tumor suppressors

P53: (-) P21 → (-) CDK1; promote DNA repair & apoptosis

Rb: Binds E2F → (-) G1/S transition

P21: pathway mentioned

P16: (-) CDK4/6 → (-) Cyclin D → Rb remains

BRCA1/2: (+) DNA repair

NF1: (-) RAS pathway

BCL protein family

Pro-survival (inhibit apoptosis)

- Bcl-2

- Bcl-XL

- MCL-1

Pro-apoptosis

- BAX

- BAK

BH3 only proteins

- Bid

- Bad

- Bim

- Noxa

- Puma

Apoptosis pathway (intrinsic & extrinsic)

Necroptosis pathway

Platelets and their types

Content of platelet granules

- F.II, F.V, Fibrinogen

- β-thromboglobulin (inhibit heparin)

- Mitogenic proteins (TGF-β)

- vWF

- Fibronectim

- ATP, ADP

- Serotonin

- Histamine

- Calcium

Platelet activation

1. Vascular injury: exposure to subendotheloum (vwF + collagen)

2. Adhesion: vWF to GP-Ib-IX-V

3. Activation: Shape change + degranulation

4. Aggregation: Fibrinogen to GP-IIb/IIIa

5. Procoagulant activation: superactivated platelet

6. Clot stabilization: platelet contracts fibrin mesh

Most important GP receptors on platelet membranes

1. GP Ib-IX-V: vWF receptor (high shear)

2. GP Ia/IIa: Collagen receptor

3. GP VI: Collagen receptor

4. GP IIb/IIIa: Fibrinogen receptor

Glutamine-α-ketoglutarate pathway

Metabolic Syndrome

- ↑ Fasting blood-glucose

- ↑ Blood-pressure

- ↑ TAG & VLDL

- ↓ HDL

- Obesity

Lipogenic liver

Glucogenic liver

Periportal vs. perivenous hepatocytes: enzymes & pathways

Periportal vs perivenous hepatocytes: biotransformation oriented

Exogenous & endogenous cholesterol transport

Biotransformation

First pass effect definition

metabolic inactivation of a drug in the liver after oral administration, which significantly reduces the amount of active drug reaching systemic circulation.

Phase 0 of biotransformation

Transport of drugs into hepatocytes via ABC Transporters before Phase I/II biotransformation can begin

Oxidation of ethanol

Oxidation of methanol

Alcohol related fatty liver disease

Vitamin K dependent carboxylation

Classical coagulation cascade

Anticoagulants

Hemostatic balance

Fibrinolytic pathway

Iron absorption in enterocytes

Tf-TfR1 pathway

Regulation of iron homeostasis

HIF-1alpha pathway

mTOR pathway

Contact system (kallikrein)

De novo collagen synthesis

Astrocyte-neuron lactate shuttle

De novo acetylcholine synthesis

Lipoproteins and their apoproteins