MSK Hepato:

Extracellular propeptidases cleave disulfide-rich terminal extensions from the

procollagen molecule. This results in formation of water-insoluble triple helical
collagen fibrils.
Alkaptonuria is an autosomal-recessive disorder in which the lack of homogentisic
oxidase blocks the metabolism of phenylalanine and tyrosine at the level of
homogentisic acid, leading to an accumulation of homogentisic acid. Homogentisic
acid excreted in the urine imparts a black color to urine, if allowed to undergo
oxidation. Alkaptonuria also causes ochronosis, a blue-black pigmentation that is
most evident in the ears, nose, and cheeks.
Marfans syndrome is due to a defect in fibrillin, an extracellular glycoprotein that is
abundant in the zonular fibers of the lens, the periosteum and the aortic media. The
different locations of fibrillin production explain the varied clinical manifestations of
Marfans syndrome.

Alkaptonuria is an autosomal recessive disorder caused by a deficiency of the

enzyme homogentisic acid oxidase, which normally breaks down the tyrosine
byproduct homogentisic acid (also called alkapton). Accumulated homogentisic acid
causes pigment deposits in connective tissues throughout the body.

Gout can occur with increased frequency in patients with activating mutations in 5'-phosphoribosyl-1'-pyrophosphate
(PRPP) synthetase due to an increased production of purines which results in hyperurlcemla.

Colchicine is useful in the acute management of gouty arthritis because it inhibits the chemotaxis of
neutrophils by preventing microtubule formation.
The IP3 second messenger system begins with hormone binding and G-protein
activation leading to activation of phospholipase C. Phospholipase C forms
diacylglycerol and IP3 from phospholipids, and IP3 causes an increase in intracellular
calcium, which then activates protein kinase C.
snRNPs (small nuclear ribonucleoproteins) are synthesized by RNA polymerase II in the nucleus. They
help to remove introns from the RNA transcript and are thus necessary for synthesis of messenger RNA.

Ehlers-Danlos syndrome is a heritable connective tissue disease typically associated

with abnormal collagen. EDS usually manifests clinically as over-flexible
(hypermobile) joints over-elastic (hyperelastic) skin, and fragile tissue susceptible to
bruising, wounding, and hemarthrosis.
Procollagen is synthesized by a series of steps within the endoplasmic reticulum of
cells such as fibroblasts. This molecule is then released into the extracellular space
by transport through the Golgi apparatus and converted into collagen by procollagen
peptidases that cleave the water soluble, non-helical N- and C-terminal portions of
the procollagen molecule from procollagen to form collagen. Collagen monomers are
then covalently crosslinked with each other after certain residues are oxidized by
lysyl oxidase.

Glycogen degradation is coupled with skeletal muscle contraction due to calciummediated myophosphorylase activation. Muscle is stimulated to contract by the
neurotransmitter acetylcholine at the neuromuscular junction. This stimulation
causes depolarization of the muscle cell and release of calcium from the sarcoplasmic
reticulum into the cytosol. Increased calcium in the cytosol binds troponin C to cause
muscle contraction, and it also activates muscle glycogen phosphorylase to provide
energy for the working muscle.
Hydroxylation of proline and lysine residues in the collagen precursor occurs in the
RER and requires vitamin C as a cofactor. Terminal peptide cleavage and collagen
fibril crosslinking occur in the extracellular space.
Glycine is the most abundant amino acid in the collagen molecule. It occurs in AT
LEAST every third amino acid position. The amino acid formula of collagen is (-Gly-XY-) 333.