Chapter 18 - Amino Acids, Peptides, and Proteins

Amino acids serve as the structural subunits of…

peptides and proteins

Amino acids play a diverse role in these three things…

metabolism, neurotransmission, and intracellular signaling

Peptides serve as ___ and control ___

autocrine and endocrine signaling molecules

appetite, vascular tone, electrolyte homeostasis, carbohydrate and mineral metabolism

Longer peptide chains are

proteins

Proteins serve as these 8 things

1. intracellular and extracellular structural components

2. biologic catalysts

3. mediators of contractility and motility

4. agents of molecular assembly

5. ion channels and pumps

6. molecular transporters

7. mediators of immunity

8. components of intracellular and intercellular signaling networks

Define proteome

represents the complete set of proteins in an organism or compartment of an organism such as the plasma space

CLS focuses on the plasma space

Amino acids are organic compounds consisting of what 2 groups

amino group (-NH2)

carboxyl group (-COOH)

At physiologic pH (7.4), the amine and carboxyl group carry what charges

amine group (+)

carboxyl group (-)

The pH at which ionizable groups exist equally as charged and uncharged forms is referred to as the…

pK

the pH at which an amino acid or other molecule has a net charge of 0 is referred to as the…

isoelectric point (pI)

Women vs Men daily protein requirements

W = 46 g/day

M = 56 g/day

Dietary protein is digested by…

proteases in the stomach and small intestine to yield amino acids

8 amino acids that are not synthesized by humans, so they are essential in our diets are

1. isoleucine

2. leucine

3. lysine

4. methionine

5. phenylalanine

6. threonine

7. tryptophan

8. valine

meat, milk, eggs, and fish offer full range of essential amino acids

albumin and prealbumin are sometimes used to assess the adequacy of ___ supply

amino acid

amino acid metabolism serves as scaffolds for the synthesis of many…

…that play a role in energy production

hormones, nucleotides, lipids, signaling molecules, and metabolic intermediates

When do amino acid concentrations tend to peak

12pm to 8pm

When do amino acid concentrations tend to trough

12am to 4am

most amino acids undergo glomerular filtration, but are efficiently reabsorbed in the…

proximal renal tubules

assessment of amino acids in blood, urine, and spinal fluid has been applied to the detection of…

inborn errors of metabolism

ex. homocysteine as a marker for vitamin B12 and folate status

Natriuretic peptides consist of…

atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)

Which natriuretic peptides are highly expressed in cardiac tissue

ANP and BNP

circulating concentrations increase rapidly in response to increased cardiac filling pressures that are characteristic of heart failure

Angiotensin (peptide)

Renin is secreted by the afferent arterioles of the kidney in response to decreased blood flow and sodium delivery

Vasopressin (peptide)

Arginine vasopressin (AVP) or antidiuretic hormone (ADH)

stored and secreted by the posterior pituitary gland

primary target is the distal convoluted tubule and collecting duct, where it acts to promote water reabsorption (inhibits urine production)

Conditions affecting Vasopressin secretion

Diabetes insipidus: faulty secretion or end-organ resistance

Head injury, tumors, and some meds may induce secretion, resulting in fluid overload

Protein structure classes

primary, secondary, tertiary, quaternary

Proteins: ligands and prosthetic groups

provide additional functional and structural elements, such as metals or lipids

proteins without their associated ligand are referred to as apoproteins

• apolipoproteins lack a full complement of lipid

What physical properties serve as the basis of methods to seperate proteins

• differential solubility

• molecular size

• molecular mass

• electrical charge

• surface adsorption

• affinity chromatohraphy

the 12 most abundant proteins represent more than __% of total protein mass

95%

Albumin alone represents more than __% of the total mass of protein

50%

Proteins and substances smaller than albumin are cleared from circulation by glomerular filtration, unless…

they are bound to a larger carrier molecule

Define plasma

fluid portion of blood in presence of an anticoagulant

Define serum

fluid component of blood after the blood is allowed to clot

*typically used for chemistry tests

Proteins in serum and plasma: Prealbumin

• transports 10% of circulating T3 and T4

• concentrations often used as an indicator of protein nutrition

• proportionally greater component of CSF

Proteins in serum and plasma: Albumin

• most abundant plasma protein in most body fluids

• most lab assay albumin in plasma or serum samples by dye-binding

Proteins in serum and plasma: a1-Antitrypsin (AAT)

• concentration typically 70-200 mg/dL

• deficiency is inherited in an autosomal codominant resulting in liver and pulmonary disease

Proteins in serum and plasma: Ceruloplasmin (Cp)

• contains 95% of circulating copper

• failure to incorporate copper into Cp causes Wilson disease

Proteins in serum and plasma: Haptoglobin

• scavenges hemoglobin

• depletion indicates intravascular hemolysis

• measurement performed to assess possible transfusion reactions or other causes of hemolysis

Proteins in serum and plasma: Transferrin

• principle plasma transport for ion

• indirect assessment of concentrations may be inferred by TIBC

Proteins in serum and plasma: B2-Microglobulin

• noncovalently bound light chain subunit of class I MHC molecules

• High [ ] seen in renal failure, inflammation, and neoplasms associated with B lymphocytes

• *More light chains created than needed to make Ig

Proteins in serum and plasma: C-reactive protein (CRP)

• strongest acute phase reactants

• plasma [ ] rising 1000-fold after MI, stress, trauma, infection, inflammation, surgery, or neoplastic proliferation

• [ ] higher in bacterial infection

• mildly elevated [ ] associated with cardiovascular disease

Proteins in serum and plasma: Complement

• > 20 proteins

• recruit phagocytes for clearance of foreign pathogens and destruction of foreign organisms

• classical, alternative, and lectin

• lab analysis divided into 5 categories

  • complement function/activity

  • individual component [ ]

  • activation fragments of complement components

  • autoantibodies against complement components

  • genetic studies of complement genes

Proteins in serum and plasma: Immunoglobulins

• IgA, IgG, IgM, IgD, and IgE

• free light chains

  • BJ proteins if found in urine (kappa or lambda)

Acute Phase Reactants

systemic inflammation in response to infection, tissue injury, or inflammatory disease triggers changes in hepatic production

• mediated by IL-6 and other cytokines

Negative acute-phase reactants

synthesis is downregulated

albumin, transferrin, prealbumin

Positive acute-phase reactants

increase several fold and reach max within 2-5 days after an acute insult

AAT, Hp, Cp, C4, C3, fibrinogen, and CRP

Serum protein electrophoresis

• serum used to avoid a fibrinogen band

• only a few of the most abundant proteins are visible

• detection of monoclonal gammopathies

  • multiple myeloma

• “overabundance of protein”

Immunofixation electrophoresis

• employs antisera targets to specific proteins rather than nonspecific dyes

• specific lanes of the gel are overlaid with antisera to kappa and lambda light chains, as well as gamma, mu, and alpha heavy chains

• helps identify the “specific” type of Ig

CSF and proteins

• protein [ ] 100-fold lower than plasma

• different protein composition

• obtained by lumbar puncture

• prealbumin, albumin, and transferrin predominate

• viral meningitis, encephalitis, increased intracranial pressure, trauma, and hemorrhage may all compromise the BBB resulting in increased CSF protein