introduction to medical biochemistry

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  1. 4 types of biomolecules and their subtypes examples
    • macromolecules - DNA, proteins, carbohydrates, lipids
    • metabolites - glucose, atp, hormones, neurotransmitters
    • electrolytes - cations, anions, etc
    • xenobiotics
  2. macromolecules function
    • can form large complex structures
    • chemical polymers of a set of monomers or non covalent assemblies of smaller units
    • emergent properties resulting in folding and structure allows them to perform unique activities
  3. metabolites function
    small molecules that are intermediates in biochemical pathways or act as regulators of function
  4. electrolytes function
    small ions present in high conc
  5. xenobiotics function
    • foreign compounds that the body must degrade or excrete before they increase in amount and cause damage to the body
    • not synthesized by the body or part of normal metabolism
  6. biomolecules
    function
    macromolecule assemblies
    small molecule assembly
    • F: enzymatic, structural, movement, information carrying, compartmentalization
    • MA: ribosomes, membranes, chromosomes, starch, glycogen
    • SMA: lipids to membranes, nucleotides to DNA, amino acids to peptides to proteins
  7. biomolecular macromolecules and their function 4
    • carbohydrates - energy, structure, immunity
    • nucleotides - carry info, energy
    • proteins - chemistry and structure
    • membranes - compartmentalization (seperates into sides and catergories)
  8. biochemistry of medicine is the catabolism and anabolism of a substance
  9. catabolism is food uptake, absorption, distribution, storage

    anabolism is synthesis, polymerize, function, and renewal
  10. ****some diseases related to errors in medical biochemistry ex

    they can be from genetic mutations or can be caused by something complex like an infection of high blood sugar
    • metabolic syndrome disease
    • congenital diseases
    • vitamin deficiencies
    • cancer
    • cardiovascular disease
  11. function of the macromolecule carbohydrates
    • energy 
    • store energy
    • attaches to lipids to form glycolipids to act as immune recognition and a physical barrier
    • attaches to proteins to form glycoproteins  that help regulate folding and structural proteins
  12. 6C carbohydrate monomers 4
    5C carbohydrate 2
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    • glucose-epimer
    • fructose
    • galactose-epimer
    • mannose-epimer

    • ribose
    • deoxyribose
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    • contains aldehyde or ketone that permits cyclization (a formation of one or more carbon/hydrogen rings)
    • the central carbons are asymmetric which constitute a sterocenter (has 3 diff attachments) indicate direction the hydroxyl group is drawn (fischer projections)
    • upon cyclization (formation of the ring) the 1 position carbon becomes a stereocenter, is reversible but the cycle forms are favored. the two forms of glucose are either alpha (up) or bet (down)
    • most simple sugars are reducing (have a free aldehyde and ketone group) except sucrose due to linkage
  14. 3 small saccharides types and sugar types
    • sucrose - glucose and fructose
    • lactose - glucose and lactose
    • **lactose intolerant due to lack of lactase**
    • maltose - di-glucose (alpha 1-4)
    • **results from starch/glycogen breakdown in gut**
  15. sugars form small molecules as dimers or trimers  (formed complexes of monomers (a molecule of low molecular weight capable of reacting with identical or
    different molecules of low molecular weight to form a polymer))
    name 4 saccharides links
    • sucrose - fructose and glucose linked at alpha 1-2
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    • lactose - galactose and glucose in a beta 1-4 link
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    • maltose - 2 glucose molecules in a alpha 1-4 linkage same as glycogen
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    • maltodextrin - 3 or more linearly joined glucose units in alpha 1-4 link
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  16. Sugar polymers of carbohydrates 4 and characteristics
    Starch (amylose – linear non branched chain of glucose molecules connected by alpha1>4 glycosidic bonds, less digestible – Amylose forms more compact, less hydrated structures, and is digested much slower (fewer end points, and the more compact, less hydrated structure makes it less accessible to digestive enzymes (needs to be cooked if contained)

    Amylopectin – glucose storage in plants that animals can digest. Alpha 1-4 glycosidic bonds with branch points of alpha1-6 glycosidic bonds)

    Glycogen – glucose storage in animals, linear alpha 1-4 glucose chains plus branches form by alpha 1-6 glycosidic bonds

    Cellulose – most abundant biomacromolecule, this is a dietary fiber. It is not digested to a significant extent in humans because we lack an enzyme to break the β(1-4) glycosidic bond, as do other mammals.
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  18. Glycolipids links to various sugar monomers and modified sugars, what are some sugars
    N-acetyglucosamine

    n-acetygalactosamine

    n-acetyl-neuraminic acid

    Galactose

    Fucose

    Mannose
  19. How glycolipids are used as antigens?
    Glycolipids create carb trees attached to lipid proteins i.e blood antigens (molecule capable of inducing an immune response to produce an antibody in the host organism, the precise linkage and order depends on the individual, and recognition of those carbohydrates helps to determine if it is seen as foreign or self
  20. glycoproteins characteristics 5
    modified sugar residues – n-acetyl glucosamine and glucuronic acid

    polymerization

    attachment to Ser residues on proteins

    can be structural components and can form integral and substantial part of connective tissue

    the chondroitin sulfate repeat at the end provides a lot of negative charge to sugar chains to keep them hydrates and apart providing elasticity required for connective tissue
  21. protein functions 8
    source of E

    source of AA to rebuild new proteins

    movement

    communication, receptor signaling

    transport

    structure

    catalysts

    product of information carried on the genome
  22. amino acids  that fall into each catergory

    charged 5

    polar 5

    non polar 7

    small 2

    cyclic 1
    C: Anionic: glu, asp Cationic: arg, lys, his

    P: ser, thr, gln, asn, cys

    NP:leu, Ile, met, val, phe, tyr, trp

    S: ala glycine

    Cy:Pro
  23. 7 functions of nucleotides
    Information storage – DNA

    Information transfer – mRNA

    Post transcriptional processing – miRNA

    Translation – rRNA and tRNA

    Catalytic enzymatic function

    Energy transduction

    Cofactors
  24. Nucleotides forms of small building blocks, cofactors, DNA/RNA
    S: ATP, GTP, CTP, UTP (deoxy forms: Datp, dgtp, dctp,dttp

    C:nicotine adenine dinucleotide (NAD), flavine adenine dinucleotide (FAD), flavine mononucleotide (FMN), coenzyme A (CoA)

    D/R: mrna, trna, rrna, sirna, mirna
  25. Components of nucleotides 3
    Sugar: Ribose 5 C sugar, deoxy ribose

    Base: purines 2 = adenine, guanine, pyrimidines 1=cytosine, thymine , uracil

    **attaches to 1 carbon of sugars

    Phosphate: forms the backbone linkage at the 5’and 3’ positions of the ribose or deoxyribose



    DNA 5-3 reading, A=T G-=C, anti-parallel, same amount of AT as CG

    RNA amounts of AUCG varies, will form base pairs but will be single stranded or loops, ratios of each help determine if DNA or RNA
  26. RNA characteristics 4
    Can be amorphous (no defined structure): mrna (long strands), sirna (small post transcription reg), mirna (micronRNA)

    Have discrete structures: tRNA, rRNA

    Have transient structures mrna

    All carry info
  27. Functions of RNA 5
    Structural (ribosomes)

    Catalytic (ribozymes)

    Carriers (trna)

    Transcriptional regulation (splicing)

    Translational regulation (sirna,mirna)
  28. Lipids characteristics 2
    Non polar or amphipathic molecules (constituents of micelles, vesicles, and bilayer sheet

    Not soluble, forms micelles, vesicles, or membrane sheets and become dispersed

    Constituents (part of) membranes, fats, oils, waxes, detergents
  29. Waxes characteristics 3
    Sugar: Ribose 5 C sugar, deoxy ribose

    Base: purines 2 = adenine, guanine, pyrimidines 1=cytosine, thymine , uracil

    **attaches to 1 carbon of sugars

    Phosphate: forms the backbone linkage at the 5’and 3’ positions of the ribose or deoxyribose



    DNA 5-3 reading, A=T G-=C, anti-parallel, same amount of AT as CG

    RNA amounts of AUCG varies, will form base pairs but will be single stranded or loops, ratios of each help determine if DNA or RNA
  30. Oils characteristics 2
    Hydrophobic liquid

    Can be hydrocarbons, triglycerides, or FA of varying length but can be other chemical types of as well
  31. fat characteristics
    tryglycrides, hydrophobic solid
  32. Detergents characteristics 2
    Natural or synthetic amphiphilic compounds that act as surfactants

    from membrane lipids in that they tend to not form bilayers, but rather form micelles. In most cases this is because the polar head group is bigger than hydrophobic acyl chain
  33. how detergents are able to dissolve oils and fats?
    detergents have the ability to carry hydrophobic molecules in their cores, thus effectively dissolving oils and fats.
  34. Lipids function 5
    Energy storage                

    Compartmentation (division into separate parts)

    Signaling molecules (steroids)

    Vitamins

    Dietary lipids used for heart disease

    **key to lipids is their hydrophobicity

    **structure polar head group, glycerol backbone, fatty acids

    **middle glycerol positions contains an unsaturated fatty acid. This is typical for many lipids. The fatty acid in this position can be released in response to hormones and act as a signaling molecule or precursor
  35. Amphipathic define
    Molecules are those with polar and non polar parts and can form bilayers, vesicles, micelles

    **depending on shape they are classified as detergents (form micelles) or membranous lipids – can form bilayers/monolayers as vesicles or membranes
  36. structure of some phospholipids, the glycerol-phospholipids
    One major class of lipids is the glycerol-phospholipids 6

    They have a glycerol backbone

    They have two fatty acids

    The middle position (2-position) fatty acid is typically unsaturated.

    The end position fatty acid may be saturated.

    They have a phosphate at the other end of the glycerol

    They can have a headgroup attached to the phosphate .
  37. Headgroups for glycerol-phospholipids 4
    Ethanolamine

    Choline

    Serine

    Inositol

     

    **The headgroups defines the charge properties and the cell-signaling properties of the lipids.

    In addition to constituting a major structural, lipids participate specific cell signaling events

     

     

    Vesicles, or liposomes, are bilayers enclosing a limited aqueous compartment. They are typically spherically shaped, the bilayer forming the outer layer of the sphere

     

    Bilayers occur in vesicles, but may also form larger, flatter sheets that constitute plasma

    membranes, the endoplasmic reticulum, etc etc.Bilayers have two monolayers juxtaposed with their non-polar (hydrophobic) parts together,

    and the polar parts interaction with water. To form vesicles or bilayer sheets, the lipids that constitute them must be amphipathic
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  39. Metabolism define
    is the interconversion of food, storage molecules and energy through highly regulated chemical reactions that adapt to changes in food supply and energy demands.
  40. Catabolism define
    the conversion of complex food and storage molecules (complex carbohydrate,

    protein and fat) into simpler components (monosaccharides, fatty acids, aminoacids) that

    can be utilized for energy.
  41. Anabolism define
    The use of simple metabolites (simple sugars, fatty acids and amino acids) to generate more complex molecules for storage (glycogen, triglycerides, and protein) and for maintenance and growth (new proteins, membranes), including specialized molecules such as hemes, cholesterol, and nucleotides.
  42. 3 main E storage molecules name, type, location
    Fat: tyglycerides (glycerol and 3 FA chains) (major storage not converted to glucose), located in liver and muscle as adipocytes

    Protein: major storage for AA in liver and muscle, Metabolism of proteins and amino acids must include metabolic pathways for excreting nitrogenous compounds. Amino acids can be metabolized to yields glucose and E, located in muscle

    Glycogen: glucose storage (24 hour supply), located in muscle and liver, available so other mechanisms for prolonged fast
  43. The particular response of metabolism on an organ depends on the metabolic demand:

    Fed

    Fasted

    Starved

    Exercised

    Stress

    Some combination of these.

    ** he system senses the changes in demand, it provides central and peripheral responses through the endocrine system and other mechanisms. This goes through intracellular signaling pathways, to change the cellular level response. This response will be distinct for each organ. The particular response of an organ depends on its role in metabolism and its energetic needs.
  44. Liver storage and function
    stores glycogen, protein and some fat.

    It functions to maintain blood levels of glucose during the fasted and stressed state and to synthesize fat from carbohydrate and amino acids during the fed state.

    It is a major site of biosynthesis and processing between the intestines and other organs.
  45. Muscle storage and function
    is the major storage site for protein and glycogen. Muscle lacks glucose-6-phosphatase and cannot make glucose for other organs. Because of its glycogen stores, muscle can function anaerobically for a short time.
  46. Adipose storage and function
    tissue serves as the major storage site for triglycerides (FAT)
  47. Kidney storage and function
    is specialized for nitrogen metabolism and the excretion of urea.
  48. Intestine storage and function
    serves to absorb nutrients from digested food and pass them on to the liver and blood.
  49. Red Blood cells storage and function
    (erythrocytes) are specialized for oxygen delivery. Having no mitochondria, they rely exclusively on anaerobic metabolism for energy.
  50. Brain storage and function
    normally uses glucose for its fuel and metabolizes little fat.

    During starvation or long fast, brain can adapt to use ketone bodies for fuel
  51. Exergonic steps that are regulatory in glycolysis:
    Hexokinase

    Phosphofructokinase

    Pyruvate kinase
  52. Pyruvate Dehydrogenase (PDH): A major regulated step functions 3
    Has a number of important vitamins and cofactors. Deficiency in these causes

    metabolic problems.

    Regulates movement of pyruvate to Acetyl CoA.

    Regulates by Acetyl CoA, NADH, and by phosphorylation.

    Regulated indirectly by hormones
  53. Glycolysis
    The transformation of glucose to pyruvate; generates small amount of energy quickly, takes place in cytoplasm
  54. TCA cycle
    Breakdown of Acetyl (Acetyl CoA) to CO2 with production of reducing equivalents (NADH and CoQH2, takes place in mictochondria, energy used GTP, 3nADH, 1 FADH2, waste 2CO2, regulate substrate and cofactor
  55. Beta oxidation
    The breakdown of fatty acids to Acetyl CoA; this takes place in the mitochondria. It ultimately makes energy (ATP) from fat stores
  56. Oxidative Phosphorylation
    electron transport. Converts high energy electrons (reducing power) to ATP and makes water from oxygen, takes place in mitochondria

    **Note Pyruvate ends Glycolysis and is a central intermediary with several possible fates.
  57. Acetyl CoA is the substrate for the TCA cycle  also a central intermediary:


    Sources of AcCoA:
    Fates of AcCoA:
    • Pyruvate
    • Beta-oxidation of fatty acids
    • Ketone bodies


    • TCA cycle entry
    • FA synthesis
    • Ketone body production
  58. TCA cycle intermediates functions
    • Serve as start points in anabolic reactions
    • Serve as end points for catabolism of many amino acids
    • Are involved in other pathways and transport mechanism
  59. Fates of pyruvate 5
    Lactate (anaerobic metabolism)

    AcetylCoA – aerobic energy production, fatty acid synthesis

    Oxaloacetate – anapleurotic reactions (refilling of TCA intermediates) or the first reaction point of gluconeogenesis (Liver glucose production)

    Ethanol – in microorganisms during fermentation.

    Alanine – Nitrogen transport
  60. TCA cycle regulation:
    • TCA cycle produces reducing equivalents in the form of NADH, and CoQH2
    • TCA cycle produces 1 ATP equivalent as GTP.
    • TCA cycle produces 2 CO2 from Acetyl CoA.
  61. Enzymatic at the following enzymes fr regulation
    Citrate synthase

    Isocitrate dehydrogenase

    Alpha-ketoglutarate dehydrogenase


    **By limiting cofactors (NADH in particular)

    **By ATP and ADP concentrations in the mitochondrion.

    **By Mass action coupling to oxidative phosphorylation
  62. Amino acid catabolism can be used for the following 3
    energy (muscle and other tissues)

    urea cycle, converts AA and Co2 to urea

    Glucose synthesis in the liver or kidney (gluconeogenesis) during fasting

    **proteins are degraded by proteases and by the proteasome (targeted degradation)
  63. Metabolic pathways feed into pathways via one or more of these 3 ways
    Pyruvate (glucogenic)

    Acetyl CoA (ketogenic)

    TCA cycle intermediates
  64. Amino acids classifications in metabolic pathways 3
    Ketogenic – feed only into acetyle coa

    Glucogenic – those that feed into pyruvate or replenish TCA cycle intermediates, can be glucogenesis precursors

    Ketogenic and glucogenic – breakdown results in both acetyl coa and TCA cycle intermediates
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  66. An adequate understanding of metabolism and its regulation are essential for the management of human health and disease.
    Inborn errors in metabolic pathways link genetics to defects in some aspect of metabolism.
    A “healthy” diet including essential nutrients that balances energy intake and

    expenditures is important to human health.
    Common metabolic disorders such as diabetes, obesity, alcoholism are a leading cause of death in humans.
    The management of critically ill patients requires a knowledge of basic metabolism and its regulation
  67. Where do we get energy?
    Solar energy drives the energetics of life on the earth.

    Plants use light (photons) to split water and to fix CO2

    This produces:Oxygen in the atmosphere 

    Stored reducing equivalents in the form of the following:

    Fats, Oils,Carbohydrates,Proteins

    Metabolism harvests reducing equivalents (food), and recombines them with

    oxygen. This generates the energy that supports:

    Temperature Biosynthesis Mechanical movement The results are water and CO2
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    A thermodynamic quantity that is the difference between the internal energy of a system and the product of its absolute temperature and entropy; the capacity of a system to do work, as in an exothermic chemical reaction
  69. Macronutrients define
    Dietary proteins, sugars, and fats digested in mouth stomach and intestines yiled amino acids, simple sugars and FA
  70. Micronutrients define
    Things require or taken in smaller quantities, i.e nucleotides, vitamins, etc.
  71. Fatty Acid Synthesis
    • Occurs principally in the liver
    • Occurs when there is sufficient carbohydrate influx to raise Acetyl CoA concentrations beyond what is needed for local energy needs.
    • Acetyl CoA is turned into fatty acids and combined with glycerol phosphate to make triglycerides.
    • Triglycerides are packaged into lipo-protein particles called VLDL (very low density lipoprotein).
    • VLDL is exported to the circulation where it will traffic the triglycerides to adipose

    tissue (when fed)
  72. fatty acid synthesis requirements 2
    ATP from oxi phos

    NADPH from hexo monophosphate shunt aka pentose phosphate pathway (can also produce ribose as ribose-5-phosphate)
  73. Mitochondria – power house of cell characteristics
    Contains the enzymes for the TCA cycle, including pyruvate dehydrogenase.

    Oxidative phosphorylation occurs here and includes:: Electron transport, Proton gradient, ATP synthesis

    Conversion of glucose to reducing power to proton gradient to ATP –energy transduction.

    Converts oxygen to H2O – O2 is the source of oxidative energy. Creates a proton electrochemical gradient

    **differnce between chemical gradient –concentration & Electrical gradient –voltage.Reminder that everything has to get in and out by transport
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  75. Gluconeogenesis purpose, location, end result
    Purpose: To maintain circulating glucose concentrations and prevent hypoglycemia during long-term fasting (>4hr). Insulin is low, glucagon high. Cortisol, epinephrine and norepinephrine may also be high. Cortisol, epinephrine, and nonepinephrine may also be high

    Occurs in: The liver and kidney.

    What it accomplishes: Synthesizes glucose for export to the circulation.
  76. How gluconeogenesis works?
    During fasting, insulin drops and glucagon increases. Glucagon stimulates glycogen breakdown to supply circulating glucose, and with extended fasting, will then also induce gluconeogenesis. Gluconeogenesis is the synthesis of glucose from precursors. Pyruvate is considered a start point of gluconeogenesis.Pyruvate can not be directly reversed to phosphoenolpyruvate and so goes through two other reactions:Conversion to Oxaloacetate & Conversion of Oxaloacetate to phosphoenolpyruvate The intermediate oxaloacetate is a TCA cycle intermediate and allows TCA cycle to feed into gluconeogenesis.From phosphoenol pyruvate, glycolysis is reversed until Fructose 1,6 bisphosphate, where  a separate enzyme is required to convert it to Fructose-6-phosphate. The reversal results in Glucose -6-phosphate. Another gluconeogenic enzyme,

    glucose phosphatase, is required to convert G6-phosphate to glucose
  77. gluconeogenic precursors 4
    lactate – anaerobic glycolytic metabolism

    alanine and glutamine from protein breakdown

    glycerol from fat breakdown

    other products that feed into the TCA cycle
  78. regulation of metabolism can undergo 3 mechanisms and their function
    metabolite -  feed forward, feedback inhibition or activation, cofactor/substrate restrictions, allosteric protein regulation

    phosphorylation – often hormone mediated (insulin generally dephosphorylates; glucagon activates protein kinase A)

    changes in protein activity – changes in transcription/translation, changes in glucose transporter (delivery)
  79. feedback inhibition of a linear pathway define
    the product blocks further entry into the pathway by inhibiting the first step
  80. feed forward activation define
    high concentration of A promotes its own entry into the pathway
  81. energy change regulation define
    common in glycolysis, ATP inhibits further production of ATP whereas ADP activates the pathway to generate more ATP
  82. how regulation of activity of TCA cycle entry by phosphorylation?
    Pyruvate dehydrogenase is the enzyme regulated by phosphorylation

    Specific kinase can phosphorylate and inactivate PDH.

    A specifici phosphatase can remove the phosphate and render PDH active.

    The Kinase and phosphatase are in turn regulated by small molecule metabolites: ATP,

    AcCoA, NADH, and Ca2+

    **In addition, there is also more direct feedback inhibition by Acetyl CoA and
  83. How insulin promotes glucose uptake?
    on, the glucose transporter, Glut4, is delivered from internal vesicle stores to the plasma membrane to increase glucose uptake in response to insulin stimulation

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Author:
kaitiek09
ID:
333807
Filename:
introduction to medical biochemistry
Updated:
2017-09-05 15:26:22
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medical
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FUNDAMENTALS OF MEDICINE
Description:
RUSM introduction to medical biochemistry WEEK 1 FUNDAMENTALS 1
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