Biochemistry II Flashcards

Question

What is the importance of the PPP?

Answer 1

- Produces NADPH for reductions - Produces pentoses for nucleotide synthesis

Answer 2

**Synthesis:** Fatty acid biosynthesis Fatty acid chain elongation Cholesterol biosynthesis Neurotransmitter biosynthesis Nucleotide biosynthesis Superoxide synthesis **Detoxification:** Reduction of oxidized glutathione Cytochrome P450 monooxygenases

Answer 3

Intracellular ratio of NADPH/NADP+ \>\> NADH/NAD+

Answer 4

Malondialdehyde in blood - Free radicals extract hydrogen atoms from lipid to form lipid radicals - reaction with O2 propagates radical chain rxn and forms lipid peroxy radical and lipid peroxide - electron rearrangements result in lipid degredation

Answer 5

Antioxidants i.e. vitamin E

Answer 6

Glutathione - Glutathione with free sulfhydryl group - Reduces hydrogen peroxide and lipid peroxides by formation of disulfide GSH + GSH ==\> GSSG (Enzyme: Glutathione peroxidase) (H₂O₂ --\> 2H₂O)

Answer 7

Glucose-6-Phosphate Dehydrogenase allows for the oxidative reactions of the PPP to produce NADPH -NADPH is necessary for Glutathione defenses against ROS damage - Without G6P Dehydrogenase, cells are vulnerable to ROSs

Answer 8

- X-linked enzymopathy affects males Affected males usually have 10% normal enzyme activity, sufficient to handle normal oxidative stress - Crisis occurswhen cells are assaulted by high levels of oxidants (i.e. antimalarials) - RBCs are most susceptible because they cannot repair oxidative damage by replacement of lipids, proteins, etc.

Answer 9

Occur in erythrocytes of G6P deficient people after drug exposure - they are particles of denatured hemoglobin that has become crosslinked, adhering to the RBC membrane visible when stained with basic dyes

Answer 10

In a normal individual, NADPH depletion is fast, but so is the G6P dehydrogenase rxn In a G6P dehydrogenase deficient individual, NADPH depletion is just as fast, but they are unable to produce NADPH to keep up with the depletion **G6P Dehydrogenase rxn is too slow**

Answer 11

1. **Immediate**: "Phosphagens" (ATP and creatine-P) 2. **Short Term**: Anaerobic glycolysis 3. **Long Term**: Aerobic - Aerobic glycolysis - fatty acid oxidation - The 3 systems are used in overlapping sequence

Answer 12

Because they do not have the ability to replace and repair affected structures (lipids, proteins, etc) and, thus, cannot otherwise repair oxidative damage

Answer 13

Transketolase is dependent on thiamine pyrophosphate as a cofactor Reactions in PPP: **Glyceraldehyde-3-P + Sedoheptulose-7-P ==\> Fructose-6-P + Erythose-4-P** **Erythose-4-P + Xylu****lose-5-P ==\> Fructose-6-P + Glyceraldehyde-3-P**

Answer 14

Increased blood flow

Answer 15

**Phosphagens:** ~10s **Anaerobic:** ~2min **Aerobic:** ~2hrs

Answer 16

Phosphagen system: Creatine Phosphate contains a high energy bond that can easily be given to ADP or AMP: ADP + phosphocreatine ==\> ATP + creatine Allows for quick production of ATP until phosphocreatine is exhausted

Answer 17

When measured, PCr and Glycogen stores remain consistent through exercise - no *net* loss was observed When in actuality, PCr and Glycogen stores are restored between muscle twitches - net loss is only observed during intense exercise because there is not enough time between twitches to restore levels

Answer 18

GLUT-4 Transporters Hexokinase PFK-1 Glycogen phosphorylase Carnitine Palmityl Transferase I (CPTI)

Answer 19

- Activated by insulin and/or exercise - Activated by AMP (via AMP-PK) More GLUT-4 transporters are transported to the cell surface to allow more glucose into the cell

Answer 20

Through Feedback Inhibition: Limits drain on blood glucose when using glycogen Hexokinase is inhibited by it's product, Glucose-6-P Lack of inhibition can result in depleted phosphate stores, while lack of activation by substrate allows unphosphorylated glucose to leave the cell

Answer 21

- Activated by AMP (Allosterically), epinephrine, Ca²⁺ **Epinephrine** activates Adenylate cyclase **Ca²⁺ and Ca²⁺-calmodulin** help push the reaction of Phosphorylase kinase A (inactive) to Phosphorylated Phosphorylase kinase (active) **AMP** helps push the reaction of Phosphorylase B (inactive) to Phosphorylated Phosphorylase B (active) (which breaks down glycogen)

Answer 22

- Activated by insulin, F-2,6-BP, and AMP (allosterically) - Inhibited by citrate, and ATP

Answer 23

It is blocked by malonyl-CoA -Acetyl CoA Carboxylase-2 (ACC-2) synthesizes MCoA from Acetyl-CoA and CO2 (inhibited by AMP-PK) - Malonyl CoA Decarboxylase decarboxylates MCoA to AcCoA (Activated by AMP-PK)

Answer 24

Glucose transport into cell Glycolysis Glycogenolysis FA transport into Mitochondria

Answer 25

Pyruvate -\> AcCoA +CO2 TCA Cycle Beta-oxidation of FA

Answer 26

The process in which ADP controls the rate of oxphos, and the rate in which O₂ is used in the cell and ATP produced

Answer 27

Collagen Elastin Laminin

Answer 28

A major protein found in elastic fibers in the ECM of connective tissue of smooth muscle cells, endothelial and microvascular cells, chondrocytes, and fibroblasts Allow tissues to expand and contract particularly important for blood vessels

Answer 29

After Type IV collagen, most abundant protein in basal laminae provides additional structural support for tissues Able to bind Type IV collagen to other molecules present in ECM

Answer 30

**Collagen**: tensile strength of tissue (resist tearing) **Proteoglycan**: Resilliency of tissues **Elastic Fibers:** Elasticity of tissues **Laminin**: Structural support of basal lamina

Answer 31

- All types contain 3 long polypeptide chains with at least one strech wound together to form a triple-helix General sequence: **GLY-X-Y (X usually Pro, Y usually hydroxyproline or hydroxylysine)** - Right handed collagen super helix is formed by intertwining three, left-handed helical strands - collagens are glycoproteins, but the amount of carbohydrate is variable

Answer 32

Col(collagen type)alpha(chain type) i.e. three-chain a₂b structure that makes up Type I collagen = [Col(I)alpha1]₂Col(I)alpha₂

Answer 33

Accounts for 90% of total body collagen and occurs in skin, bone, tendons, cornea, soft tissues, and scars. Has the least carbohydrate a_2b = [Col(I)alpha1]₂Col(I)alpha₂

Answer 34

Osteogenesis imperfecta

Answer 35

Occurs in cartilage (made by chondrocytes) and vitreous humor 10% carbohydrate c₃ = [Col(II)alpha1]_{3
(homotrimer)}

Answer 36

Occurs mainly in blood vessel walls, other hollow organs, and fetal skin (also scars and adult soft tissue) Contains disulfide bridges between chains d₃ = [Col(III)alpha1]₃ _(homotrimer)

Answer 37

Ehlers-Danlos type 4 - aortic rupture, GI tract, pregnancy problems - skin fragility, poor wound healing --\> surgical issues

Answer 38

Collagen of basement membranes has disulfide bridges and has highest carbohydrate content non-fibrillar type, interruptions of the triple helix due to highest content of carbohydrate Mesh forming collagen All homotrimers w/different subunits (subunits 1-5): [Col(IV)alpha(1-5)]₃

Answer 39

H-bonds occur between each Gly-N-H and the C=O of the succeeding X residue on neighboring chain Hydroxylation of Y residues give a polar outside surface to stabilize overal structure with H-bonds to H₂O Every 3rd residue must be Gly since there is no room near the helix axis for the side chain of ANY other AA

Answer 40

Procollagen is formed from preprocollagen after removal of signal peptides in the ER _3 Domains of procollagen_: 1. Globular (N and C terminal) 2. Triple Helical 3. Non-triple helical Aminoprocollagen peptidase cleaves at the non-triple-helical domain near the N terminal Carboxylprocollagen peptidase cleaves the non-triple-helical domain near the C terminal

Answer 41

1. Polypeptide chains of preprocollagen are synthesized on the rER and the signal (pre) sequence is cleaved 2. Proline and lysine residues are hydroxylated by a rxn that requires O₂ (activated by Fe²⁺) and Vitamin C 3. Galactose and glucose are added to hydroxylysine residues (addition of carbohydrates) 4. Triple helix forms, and procollagen is secreted from the cell and cleaved to form collagen 5. Cross-links are produced.

Answer 42

With a lack of Vitamin C, Hydroxylation of collagen is not possible, leading to: Loss of Strength easy bruising and petechiae bad breath gum disease loss of teeth poor wound healing

Answer 43

Lysyl Oxidase is unable to work and patient presents with tissue dysfunction Lysyl oxidase converts lysine residues to aldehydes, allowing for intermolecular cross-link reactions to occur in collagen Fibers are unable to fit together in ECM

Answer 44

A heterogenous group of connective tissue disorders major manifestations are: skin fragility skin hyperextensibility joint hypermobility

Answer 45

**Defect:** Decrease in Type III collagen **Manifestation:** Arterial, intestinal or uterine rupture thin, translucent, **easily bruised skin** This is because Type III collagen is often found in blood vessels and the GI tract

Answer 46

``` **Defect:** Decreased hydroxylysine (deficiency of lysyl hydroxylase) ``` **Manifestation:** **Hyperextensible skin** and joints poor wound healing This is because hydroxylation of lysine allows for stabilization of collagen with H₂O Hbonds

Answer 47

**Defect:** N-terminal propetide not cleaved **Manifestations:** **Joint hypermobility** easily bruised skin hip dislocations Lack of procollagen cleavage prevents collagen from maturing and leaves globular regions of collagen intact

Answer 48

**Defect:** Autosomal dominant defect causing Decreased synthesis of Type I collagen **Manifestations:** Blue sclera long bone multiple fractures prior to puberty Type I collagen is prevalent in bone formation and is 90% of total body collagen

Answer 49

**Defect:** Point mutations and exon rearrangements; defects in Type I collagen (Autosomal dominant) **Manifestations:** Perinatal lethality malformed and soft, fragile bones Dark sclera absent calvarial (skull) mineralization

Answer 50

Highly osmotically active extracellular polymers with gel-like properties taht protect cells and provide tissues with **mechanical resiliency** Associated with collagen in ECM Specific properties depend on type and amount of Glycosaminoglycans (GAGs) in structure Proteo = protein cores (many per single giant molecule) glycan = carbohydrate chains (glycosaminoglycans)

Answer 51

**Hyaluronate** **Chondroitin-6-sulfate** **Dermatan Sulfate** **Keratan Sulfate** **Heparin**

Answer 52

- Autosomal Recessive disorder caused by deficiency of alpha-L-Iduronidase ==\> inability to degrate proteoglycans - Results in abnormal intra-lysosomal accumulation of dermatan and heparan sulfate ==\> cell death, organ dysfunction - Osmotically active polymers accumulate in tissues: neuronal involvement leads to delays and retardation hydrocephalus resulting from meningeal involvement etc. Diagnosis at 6-24 Months. Need to demonstrate enzyme deficiency in cultured fibroblasts from patient - Palliative care

Answer 53

- Characterized by: Developmental delays mental retardation coarse facial features with macroglossia skeletal abnormalties organomegaly CV disease; valvular dysfunction joint stiffness hydrocephalus corneal clouding umbilical and inguinal hernias