Biochem Flashcards
(15 cards)
Hodgkin lymphoma
Reed-Sternberg cells, which stain positive for CD15 and CD30.
These large cells have two nuclei, or at least a bilobed nucleus, and prominent nucleoli surrounded by pale halos (owl-eye appearance), as seen in the biopsy specimen here.
Pathognomonic for Hodgkin lymphoma and confirm the diagnosis. Other histological findings in Hodgkin lymphoma include granuloma formation and an inflammatory background that contains the following cell types in varying numbers: lymphocytes, eosinophils, neutrophils, macrophages/histiocytes, plasma cells, and fibroblasts.
Graves disease
Myxedema (nonpitting edema) is specific for hyperthyroidism due to Graves disease, which is caused by TSH receptor antibodies rather than gain-of-function mutations of TSH receptor genes.
Although the majority of symptoms of hyperthyroidism are caused by increased thyroid hormone levels (i.e., nonspecific), **myxedema and exophthalmos are specific to Graves disease. **
These findings are due to autoantibody-mediated activation of TSH receptors in peripheral tissue.
***TSH receptor antibodies stimulate dermal fibroblasts and periorbital adipocytes, thereby increasing glycosaminoglycan synthesis. **
Deposition of these mucopolysaccharides is the underlying pathogenesis of myxedema and exophthalmos, which are specific to hyperthyroidism due to Graves disease
Aldose reductase
Aldose reductase catalyzes the reduction of glucose to sorbitol, which is subsequently oxidized to fructose by sorbitol dehydrogenase enzyme.
At normal blood glucose levels, only a small part of glucose is metabolized via this polyol pathway. However, in chronic hyperglycemia due to poorly controlled diabetes, sorbitol formation increases significantly, causing osmotic damage in tissues with low sorbitol dehydrogenase activity (e.g., lens, retina, kidney, and myelin sheath). Consequently, patients present with retinopathy, nephropathy, peripheral neuropathy, and bilateral cataracts as seen in this patient.
Sorbitol dehydrogenase
Sorbitol dehydrogenase converts sorbitol into fructose, which can be used as energy substrate in the **liver and seminal vesicles. **
The activity of this enzyme is low in the retina and lens.
Hence, during chronic hyperglycemia, sorbitol can accumulate in these tissues, causing bilateral cataracts as seen in this patient.
Aldolase B
Aldolase B is predominantly expressed in the liver and converts fructose-1-phosphate to dihydroxyacetone phosphate (DHAP) and glyceraldehyde.
No specific pathologic condition has been associated with overactivity of this enzyme.
Its deficiency does however result in hereditary fructose intolerance: hypoglycemia (due to inhibition of glycogenolysis and gluconeogenesis) and vomiting following consumption of fructose-containing food
Galactokinase
Galactokinase catalyzes the conversion of galactose to galactose-1-phosphate.
Deficiency of this enzyme, not overactivation, causes mild galactosemia (galactokinase deficiency), resulting in cataract formation due to accumulation of galactitol in the lens of the eye.
Glucokinase
Glucokinase is a hexokinase isoenzyme exclusively present in the liver and beta cells of the pancreas, promoting glucose storage and insulin secretion, respectively.
Unlike hexokinase, it has low affinity and high capacity for glucose and is inducible by insulin.
Pyridoxine (vitamin B6)
Pyridoxine (vitamin B6) is an essential cofactor in the synthesis of neurotransmitters and heme, patients with a chronic pyridoxine deficiency typically present with
sensory peripheral neuropathy and hypochromic, microcytic anemia (sideroblastic anemia).
While vitamin B6 deficiency is rare in the general population, it is commonly seen in association with isoniazid (INH) use in antituberculosis treatment, because INH competes with pyridoxine in neurotransmitter synthesis.
To prevent peripheral neuropathy, supplemental pyridoxine should therefore be added to every treatment regimen that includes INH.
Leber hereditary optic neuropathy
Leber hereditary optic neuropathy typically presents with **acute monocular vision loss in a young adult followed by contralateral vision loss in the following weeks or months. **
A family history of similar ocular disease is common. The condition is passed exclusively from mother to child (as are all diseases inherited via mitochondrial DNA) since mitochondria from sperm cells are not transmitted during fertilization.
Offspring of affected males, therefore, are at the same risk as the general population (about 1 in 50,000). Other conditions that demonstrate mitochondrial inheritance include mitochondrial myopathies (e.g., MERRF or MELAS syndrome)
Protein kinase A (PKA)
Protein kinase A (PKA) is a cAMP-dependent enzyme whose activity is decreased in response to glucagon receptor antagonists.
In fasting states, glucagon raises blood glucose concentration by activating a Gs protein-coupled receptor that stimulates adenylate cyclase to produce PKA-activating cAMP.
In hepatocytes, the now activated PKA inhibits phosphofructokinase-2 enzyme, thereby reducing fructose-2,6-bisphosphate concentration and its stimulating effect on phosphofructokinase-1, the key enzyme of glycolysis. A concurrent elevation in fructose-6-phosphate concentration stimulates gluconeogenesis.
PKA additionally raises blood glucose concentration by activation of glycogen phosphorylase and a simultaneous deactivation of glycogen synthase. All of these mechanisms are suppressed by glucagon receptor antagonists, explaining their glucose-lowering effect.
Mitogen-activated protein kinases (MAP kinases)
Mitogen-activated protein kinases (MAP kinases) are a family of enzymes involved in signaling pathways that regulate cellular proliferation, differentiation, and cytokine production (e.g., insulin signaling pathway).
The MAP kinase pathway is activated via tyrosine kinase receptors (e.g., via insulin).
Janus kinases
Janus kinases participate in the JAK-STAT signaling pathway, regulating processes such as immunity, cell death, and cell division.
Upstream activation of nonreceptor tyrosine kinases by extracellular signals, such as prolactin, growth hormone, interleukins, and thrombopoietin, lead to the phosphorylation of JAK proteins, which then phosphorylate STAT proteins.
Phosphorylated STAT proteins then dimerize and relocate into the nucleus, directly regulating transcription. Glucagon antagonists are not known to influence this pathway
Guanylate cyclase
Guanylate cyclase is an enzyme that produces cGMP and regulates cGMP-dependent protein kinases and ion channels downstream.
Atrial natriuretic peptide (ANP) exerts its effect by binding to a guanylate cyclase-coupled receptor.
G proteins
🎯 Key Mnemonic: “qiss and qiq till you’re siq of sqs”
This corresponds to alpha-1, alpha-2, beta-1, beta-2, M1, M2, M3. Than D1, D2, H1, H2, V1, V2.
Receptor Type
Mnemonic
G Protein
Second Messenger
α1
q
Gq
↑ IP3/DAG → ↑Ca²⁺
α2
i
Gi
↓ cAMP
β1
s
Gs
↑ cAMP
β2
s
Gs
↑ cAMP
M1
q
Gq
↑ IP3/DAG
M2
i
Gi
↓ cAMP
M3
q
Gq
↑ IP3/DAG
D1 (dopamine)
s
Gs
↑ cAMP
D2 (dopamine)
i
Gi
↓ cAMP
H1 (histamine)
q
Gq
↑ IP3/DAG
H2 (histamine)
s
Gs
↑ cAMP
V1 (vasopressin)
q
Gq
↑ IP3/DAG
V2 (vasopressin)
s
Gs
↑ cAMP
G proteins second messenger
Receptor Type G Protein Second Messenger
α1, M1, M3, H1, V1 Gq IP₃/DAG ↑, Ca²⁺ ↑
β1, β2, D1, H2, V2 Gs cAMP ↑
α2, M2, D2 Gi cAMP ↓
